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Avian influenza

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Wet markets in China

In China , wet markets are traditional markets that sell fresh meat, produce , and other perishable goods . They are the most prevalent food outlet in urban regions of China but have faced increasing competition from supermarkets. Since the 1990s, wet markets in large cities have been predominantly moved into modern indoor facilities. Wildlife is not commonly sold in wet markets in China, but poorly-regulated wet markets have been linked to the spread of zoonotic diseases , including the 2002–2004 SARS outbreak , 2013 avian influenza outbreak , and the COVID-19 pandemic . Small-scale wildlife farming emerged in China in the 1980s and expanded in the 1990s with government support. Wildlife was banned from Chinese wet markets in 2003, with further restrictions and enforcement in 2020 following the spread of COVID-19.Since the 1990s, large cities across China have moved traditional outdoor wet markets to modern indoor facilities. In 1999, all roadside markets in Hangzhou were banned and moved indoors. By 2014, all wet markets in Nanjing were moved indoors. As of 2018, wet markets remain the most prevalent food outlet in urban regions of China despite the rise of supermarket chains since the 1990s. In 2016, a Meat & Livestock Australia study of imported meat consumers in 15 Chinese cities found that 39% of those consumers had purchased beef from a wet market in the preceding month, while the same proportion who had purchased beef from a supermarket in the preceding month. However, wet markets have been losing ground in popularity compared to supermarkets, despite the fact they may be seen as healthier and more sustainable. Reports suggest "although there are well-managed, hygienic wet markets in and near bigger cities [in China], hygiene can be spotty, especially in smaller communities." During the 2010s, "smart markets" equipped with e-payment terminals emerged as traditional wet markets faced increasing competition from discount stores. Wet markets also began facing competition from online grocery stores, such as Alibaba 's Hema stores. The trade of wildlife is not common in China, particularly in large cities, and most wet markets in China do not contain live or wild animals besides fish held in tanks. In the early 1980s, small-scale wildlife farming began under the Chinese economic reform . It began to expand nationwide with government support in the 1990s, but was largely concentrated in the southeastern provinces. Some poorly-regulated Chinese wet markets provided outlets for the wildlife trade industry that was estimated by the Chinese Academy of Engineering to employ roughly 14 million people and to be worth more than $73 billion in 2016, of which $59 billion was for fur rather than for food or medicinal purposes. In 2003, wet markets across China were banned from holding wildlife after the 2002–2004 SARS outbreak , which was directly tied to such practices. In 2014, live poultry was banned from all markets in Hangzhou due to the H7N9 avian influenza outbreak . Several provinces in China also banned the sale of live poultry following the avian influenza outbreak. The exact origin of the COVID-19 pandemic is yet to be confirmed as of February 2021 and was originally linked to the Huanan Seafood Wholesale Market in Wuhan due to its early cluster of cases, although a 2021 WHO investigation concluded that the Huanan market was unlikely to be the origin due to the existence of earlier cases. Following the outbreak, epidemiology experts from China and a number of animal welfare organizations called to ban the operation of wet markets selling wild animals for human consumption. The Huanan Seafood Wholesale Market was shut down on 1 January 2020. The Chinese government subsequently announced a temporary ban on the sale of wild animal products at wet markets on 26 January 2020, and then a permanent ban in February 2020 with an exception for Traditional Chinese Medicine ingredients, By 22 March 2020, at least 94% of the temporarily closed wet markets in China were reopened according to Chinese state-run media, without wild animals or wild meat. The reopening of wet markets led to public criticism of the Chinese government's handling of wet markets by Anthony Fauci and Lindsey Graham , although their criticisms have been attributed to semantic confusion between the terms "wet market" and "wildlife market". The World Health Organization responded with the recommendation that wet markets only be reopened "on the condition that they conform to stringent food safety and hygiene standards." In April 2020, the Chinese government unveiled plans to further tighten restrictions on wildlife trade, with instructions and financial compensation for operations that were forcibly shut down. Deutsche Welle reported that by September 2020, the Chinese government had shut down almost all wildlife farms. In 2003, wet markets across China were banned from holding wildlife after the 2002–2004 SARS outbreak , which was directly tied to such practices. In 2014, live poultry was banned from all markets in Hangzhou due to the H7N9 avian influenza outbreak . Several provinces in China also banned the sale of live poultry following the avian influenza outbreak. The exact origin of the COVID-19 pandemic is yet to be confirmed as of February 2021 and was originally linked to the Huanan Seafood Wholesale Market in Wuhan due to its early cluster of cases, although a 2021 WHO investigation concluded that the Huanan market was unlikely to be the origin due to the existence of earlier cases. Following the outbreak, epidemiology experts from China and a number of animal welfare organizations called to ban the operation of wet markets selling wild animals for human consumption. The Huanan Seafood Wholesale Market was shut down on 1 January 2020. The Chinese government subsequently announced a temporary ban on the sale of wild animal products at wet markets on 26 January 2020, and then a permanent ban in February 2020 with an exception for Traditional Chinese Medicine ingredients, By 22 March 2020, at least 94% of the temporarily closed wet markets in China were reopened according to Chinese state-run media, without wild animals or wild meat. The reopening of wet markets led to public criticism of the Chinese government's handling of wet markets by Anthony Fauci and Lindsey Graham , although their criticisms have been attributed to semantic confusion between the terms "wet market" and "wildlife market". The World Health Organization responded with the recommendation that wet markets only be reopened "on the condition that they conform to stringent food safety and hygiene standards." In April 2020, the Chinese government unveiled plans to further tighten restrictions on wildlife trade, with instructions and financial compensation for operations that were forcibly shut down. Deutsche Welle reported that by September 2020, the Chinese government had shut down almost all wildlife farms. Markets in Hong Kong are governed by the law of Hong Kong . Since 31 December 1999, Hong Kong wet markets have been regulated by the Food and Environmental Hygiene Department (FEHD).

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Avian influenza

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Influenza A virus subtype H7N1

H7N1 is a subtype of the species Influenza A virus (sometimes called bird flu virus). [ citation needed ] H7N1 was first isolated in 1972, from Eurasian siskin . A highly pathogenic strain of it caused a flu outbreak with significant spread to numerous farms, resulting in great economic losses in 1999 in Italy in turkeys .

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Panzootic/html

Panzootic

A panzootic (from Greek παν pan all + ζόιον zoion animal) is an epizootic (an outbreak of an infectious disease of animals) that spreads across a large region (for example a continent), or even worldwide. The equivalent in human populations is called a pandemic . A panzootic can start when three conditions have been met: the emergence of a disease new to the population. the agent infects a species and causes serious illness. the agent spreads easily and sustainably among animals. A disease or condition is not a panzootic merely because it is widespread or kills a large number of animals; it must also be infectious. For example, cancer is responsible for a large number of deaths but is not considered a panzootic because the disease is, generally speaking, not infectious. Unlike an epizootic, a panzootic covers all or nearly all species over a large surface area (ex. rabies, anthrax). Typically an enzootic or an epizootic, or their cause, may act as a potential preparatory factor. Contagion and infection by far play the biggest role in the dissemination and spread of epizootic and panzootic diseases. These include virulent (ex. Cattle Plague), septic (can be caused in the change in food quality), parasitic (ex. Malaria), and miasmatic infections (ex. Typhoid Fever). Many claim that an accidental morbific cause, which infects a great number of animals which ceases activity after a prolonged time period. Certain factors come into play in the spread of certain panzootic diseases, as can be seen with Batrachochytrium dendrobatidis . This infection seems to be sensitive to external conditions, particularly the environment's temperature and moisture. These factors leads to limitations on where the diseases can thrive, acting almost as its 'climate niche'. Influenza A virus subtype H5N1 , the highly pathogenic strain of influenza , was first detected in the goose population of Guangdong , China in 1996. In February 2004, avian influenza virus was detected in birds in Vietnam , increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal. In October 2005, cases of the avian flu (the deadly strain H5N1 ) were identified in Turkey . EU Health Commissioner Markos Kyprianou said: "We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia , Mongolia and China ." Cases of bird flu were also identified shortly thereafter in Romania , and then Greece . Possible cases of the virus have also been found in Croatia , Bulgaria and in the United Kingdom . However, by the end of October only 67 people had died as a result of H5N1 which was atypical of previous influenza pandemics . The enzooicity of H5N1 in birds, poultry in particular, has led to a major panzootic. As of 2012, there was an estimated 400 million birds killed from infection of the H5N1 strain of influenza. Studies have shown that H5N1 is very well adapted to domestic duck and geese, making them key in controlling the H5N1 strain and preventing future panzootic events. Presently, the highly pathogenic Asian strain of Avian Influenza is still continuing to kill poultry and wild birds alike on panzootic scales. The persistence of such a pathogen in the environment would only lead to a further continuation of panzootic scale eliminations of birds. To try to control this, scientists did research involving the shed feathers of domestic ducks to test the prevalence of H5N1. Although viral persistence was notably found within drinking water and feces, the feathers exhibited the most remaining H5N1 strain for up to 160 days. The persistence exhibited through the feathers indicates the potential for environmental contamination of not only H5N1, but also other untested viruses. White Nose Syndrome (WNS) is a rapidly spreading fungal infection responsible for killing millions of bats within the past 9 years in United States and Canada. Geomyces-destructans is the causative fungal agent of the characteristic skin lesions seen on the exposed skin, particularly on wings and nose, and in the hair follicles of affected bats. WNS has only recently been discovered, in Howe's Cave, New York during the winter of 2006–2007, but affects 25% of the hibernating species. Six species of bats have been fatally effected by this panzootic; big brown bat, small-footed bat, little brown bat, northern long-eared bat, Indiana bat, and tricolored bat, and current bat population surveys suggest a 2-year population decline in excess of 75%. The geographical range of WNS has spread throughout 33 states, and 4 Canadian provinces. The mechanism of how the infection on the skin kills bats is unclear. However, the outward cause of mortality of the infected bats depends on the stage and severity of the bat. Infected bats commonly die from starvation over winter, and can suffer from lasting damage to the wing membranes and impair summer foraging if survived the winter. One of the most abundant bat species in eastern North America, the little brown bat ( Myotis lucifugus ), could disappear from this region within 16 years. Severely infected bats emerge prematurely from hibernation, and if they survive long enough and enter a different hibernaculum, the likelihood of transmission is probably high, because they presumably carry a large load of fungal spores. Transmission of the infection is either physically from bat-to-bat contact, or from and hibernaculum-to-bat, through the exposure to spores of Geomyces- destructans that were present on a roosting substrate. Newcastle disease is a contagious bird disease affecting many domestic and wild avian species. The disease is contagious through immediate contact between healthy birds and the bodily discharges of infected birds. This includes transmission through droppings, secretions from the nose, mouth and eyes. Newcastle disease spreads quickly among birds kept in captivity, such as commercially raised chickens. Symptoms include sneezing, gasping for air, nasal discharge, coughing, greenish and watery diarrhea, nervousness, depression, muscular tremors, drooping wings, twisting of head and neck, circling, complete paralysis, partial to complete drop in egg production and thin-shelled eggs, swelling of the tissues around the eyes and in the neck, and sudden death. Newcastle disease was first identified in Java, Indonesia, in 1926, and in 1927, in Newcastle upon Tyne, England (whence it got its name). However, it may have been prevalent as early as 1898, when a disease wiped out all the domestic fowl in northwest Scotland. Its effects are most notable in domestic poultry due to their high susceptibility and the potential for severe impacts of an epizootic on the poultry industries. It is endemic to many countries. The emergence and spread of new genotypes across the world represents a significant threat to poultry. This suggests that the disease is continuously evolving, leading to more diversity (Miller et al., 2009). Unfortunately, little has been done to comprehend the procedure and advancement of new genotypes (Alexander et al., 2012). Recent vNDV have been characterized as isolates and offer evidence which proposes an emergence of a fifth panzootic initiated by highly related vNDV isolates from Indonesia, Israel and Pakistan. These virus strains are related to older strains from wild birds. This suggests that unknown reservoirs harbor new vNDV isolates capable of additional panzootics. No treatment for NDV exists, but the use of prophylactic vaccines and sanitary measures reduces the likelihood of outbreaks. Chytridiomycosis caused by a chytrid fungus is a deadly fungal disease that has wiped out 30 amphibian species across the globe and has sent overall amphibian populations in decline. The fungus Batrachochytrium dendrobatidis can be found on every continent with fertile soil and has contributed to the loss of some species of frogs and salamanders. In fact, it is estimated that 287 species of amphibians are infected with this disease in over 35 countries. These countries tend to have varied or tropical climates like those found in Central America, South America, and Africa with optimal climate conditions ranging from 17 degree Celsius to 23 degrees Celsius for the fungus to thrive. The first reported instance of the chytrid fungus was in 1998 which was found on the skin of amphibians. Since amphibians absorb essential nutrients through their skin, the fungus attaches itself to the amphibian, suffocates the amphibian, and enters the blood stream of the organism. Some symptoms that are prevalent in affected species include lethargy and loss of equilibrium and begin to die 21 days after infection. Frogs that have died and are examined show high density of the fungal spores in keratinized areas of the body such as the pelvis, mouth, and underbelly. The fungus is spread through the transportation of amphibious species by humans. Infected amphibians that have escaped or are released into the wild can carry the fungus and therefore invade the surrounding habitats of local species that are not immune to the disease. Species like the American Bullfrog and African Clawed Frog can carry this disease without experiencing symptoms or death; these kinds of species are usually to blame for the spread of the disease in undeveloped habitats. Some characteristics of amphibians that are more likely to be susceptible to the disease are the lack of various developed microbiota that live and breed on the dermis of the species as well the underdeveloped immune system in specific amphibians. Species that tend to breed in flowing water which washes away the microbiota from the skin of amphibians are more likely to become infected. Organizations across the world have tried to implement rules and regulations for the transportation of amphibians across borders to prevent the continued decline of amphibians however progress has been slow. To add to the slow progress, the only cure that exists for chytrid fungus is found within laboratories for amphibians in captivity. Because of this, there is no known way for eradicating the disease in the wild.Influenza A virus subtype H5N1 , the highly pathogenic strain of influenza , was first detected in the goose population of Guangdong , China in 1996. In February 2004, avian influenza virus was detected in birds in Vietnam , increasing fears of the emergence of new variant strains. It is feared that if the avian influenza virus combines with a human influenza virus (in a bird or a human), the new subtype created could be both highly contagious and highly lethal. In October 2005, cases of the avian flu (the deadly strain H5N1 ) were identified in Turkey . EU Health Commissioner Markos Kyprianou said: "We have received now confirmation that the virus found in Turkey is an avian flu H5N1 virus. There is a direct relationship with viruses found in Russia , Mongolia and China ." Cases of bird flu were also identified shortly thereafter in Romania , and then Greece . Possible cases of the virus have also been found in Croatia , Bulgaria and in the United Kingdom . However, by the end of October only 67 people had died as a result of H5N1 which was atypical of previous influenza pandemics . The enzooicity of H5N1 in birds, poultry in particular, has led to a major panzootic. As of 2012, there was an estimated 400 million birds killed from infection of the H5N1 strain of influenza. Studies have shown that H5N1 is very well adapted to domestic duck and geese, making them key in controlling the H5N1 strain and preventing future panzootic events. Presently, the highly pathogenic Asian strain of Avian Influenza is still continuing to kill poultry and wild birds alike on panzootic scales. The persistence of such a pathogen in the environment would only lead to a further continuation of panzootic scale eliminations of birds. To try to control this, scientists did research involving the shed feathers of domestic ducks to test the prevalence of H5N1. Although viral persistence was notably found within drinking water and feces, the feathers exhibited the most remaining H5N1 strain for up to 160 days. The persistence exhibited through the feathers indicates the potential for environmental contamination of not only H5N1, but also other untested viruses.White Nose Syndrome (WNS) is a rapidly spreading fungal infection responsible for killing millions of bats within the past 9 years in United States and Canada. Geomyces-destructans is the causative fungal agent of the characteristic skin lesions seen on the exposed skin, particularly on wings and nose, and in the hair follicles of affected bats. WNS has only recently been discovered, in Howe's Cave, New York during the winter of 2006–2007, but affects 25% of the hibernating species. Six species of bats have been fatally effected by this panzootic; big brown bat, small-footed bat, little brown bat, northern long-eared bat, Indiana bat, and tricolored bat, and current bat population surveys suggest a 2-year population decline in excess of 75%. The geographical range of WNS has spread throughout 33 states, and 4 Canadian provinces. The mechanism of how the infection on the skin kills bats is unclear. However, the outward cause of mortality of the infected bats depends on the stage and severity of the bat. Infected bats commonly die from starvation over winter, and can suffer from lasting damage to the wing membranes and impair summer foraging if survived the winter. One of the most abundant bat species in eastern North America, the little brown bat ( Myotis lucifugus ), could disappear from this region within 16 years. Severely infected bats emerge prematurely from hibernation, and if they survive long enough and enter a different hibernaculum, the likelihood of transmission is probably high, because they presumably carry a large load of fungal spores. Transmission of the infection is either physically from bat-to-bat contact, or from and hibernaculum-to-bat, through the exposure to spores of Geomyces- destructans that were present on a roosting substrate. Newcastle disease is a contagious bird disease affecting many domestic and wild avian species. The disease is contagious through immediate contact between healthy birds and the bodily discharges of infected birds. This includes transmission through droppings, secretions from the nose, mouth and eyes. Newcastle disease spreads quickly among birds kept in captivity, such as commercially raised chickens. Symptoms include sneezing, gasping for air, nasal discharge, coughing, greenish and watery diarrhea, nervousness, depression, muscular tremors, drooping wings, twisting of head and neck, circling, complete paralysis, partial to complete drop in egg production and thin-shelled eggs, swelling of the tissues around the eyes and in the neck, and sudden death. Newcastle disease was first identified in Java, Indonesia, in 1926, and in 1927, in Newcastle upon Tyne, England (whence it got its name). However, it may have been prevalent as early as 1898, when a disease wiped out all the domestic fowl in northwest Scotland. Its effects are most notable in domestic poultry due to their high susceptibility and the potential for severe impacts of an epizootic on the poultry industries. It is endemic to many countries. The emergence and spread of new genotypes across the world represents a significant threat to poultry. This suggests that the disease is continuously evolving, leading to more diversity (Miller et al., 2009). Unfortunately, little has been done to comprehend the procedure and advancement of new genotypes (Alexander et al., 2012). Recent vNDV have been characterized as isolates and offer evidence which proposes an emergence of a fifth panzootic initiated by highly related vNDV isolates from Indonesia, Israel and Pakistan. These virus strains are related to older strains from wild birds. This suggests that unknown reservoirs harbor new vNDV isolates capable of additional panzootics. No treatment for NDV exists, but the use of prophylactic vaccines and sanitary measures reduces the likelihood of outbreaks.Chytridiomycosis caused by a chytrid fungus is a deadly fungal disease that has wiped out 30 amphibian species across the globe and has sent overall amphibian populations in decline. The fungus Batrachochytrium dendrobatidis can be found on every continent with fertile soil and has contributed to the loss of some species of frogs and salamanders. In fact, it is estimated that 287 species of amphibians are infected with this disease in over 35 countries. These countries tend to have varied or tropical climates like those found in Central America, South America, and Africa with optimal climate conditions ranging from 17 degree Celsius to 23 degrees Celsius for the fungus to thrive. The first reported instance of the chytrid fungus was in 1998 which was found on the skin of amphibians. Since amphibians absorb essential nutrients through their skin, the fungus attaches itself to the amphibian, suffocates the amphibian, and enters the blood stream of the organism. Some symptoms that are prevalent in affected species include lethargy and loss of equilibrium and begin to die 21 days after infection. Frogs that have died and are examined show high density of the fungal spores in keratinized areas of the body such as the pelvis, mouth, and underbelly. The fungus is spread through the transportation of amphibious species by humans. Infected amphibians that have escaped or are released into the wild can carry the fungus and therefore invade the surrounding habitats of local species that are not immune to the disease. Species like the American Bullfrog and African Clawed Frog can carry this disease without experiencing symptoms or death; these kinds of species are usually to blame for the spread of the disease in undeveloped habitats. Some characteristics of amphibians that are more likely to be susceptible to the disease are the lack of various developed microbiota that live and breed on the dermis of the species as well the underdeveloped immune system in specific amphibians. Species that tend to breed in flowing water which washes away the microbiota from the skin of amphibians are more likely to become infected. Organizations across the world have tried to implement rules and regulations for the transportation of amphibians across borders to prevent the continued decline of amphibians however progress has been slow. To add to the slow progress, the only cure that exists for chytrid fungus is found within laboratories for amphibians in captivity. Because of this, there is no known way for eradicating the disease in the wild.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Influenza_B_virus/html

Influenza B virus

Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae . Influenza B virus is only known to infect certain mammal species, including humans , ferrets , pigs , and seals . This limited host range is apparently responsible for the lack of influenza pandemics associated with influenza B virus, in contrast with those caused by the morphologically similar influenza A virus , as both mutate by both antigenic drift and reassortment . Nevertheless, it is accepted that influenza B virus could cause significant morbidity and mortality worldwide, and significantly impacts adolescents and schoolchildren. There are two known circulating lineages of influenza B virus based on the antigenic properties of the surface glycoprotein hemagglutinin . The lineages are termed B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. The quadrivalent influenza vaccine licensed by the CDC has been designed to protect against both co-circulating lineages and as of 2016 has been shown to have greater effectiveness in prevention of influenza caused by influenza B virus than the previous trivalent vaccine. However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures. In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. For the 2024–2025 Northern Hemisphere influenza season, the US Food and Drug Administration (FDA) recommends removing B/Yamagata from all influenza vaccines. The European Medicines Agency (EMA) recommends removing B/Yamagata from influenza vaccines for the 2024–2025 seasonal flu vaccine composition. The influenza B virus capsid is enveloped while its virion consists of an envelope, a matrix protein, a nucleoprotein complex, a nucleocapsid , and a polymerase complex. It is sometimes spherical and sometimes filamentous. Its 500 or so surface projections are made of hemagglutinin and neuraminidase . The influenza B virus genome is 14,548 nucleotides long and consists of eight segments of linear negative-sense, single-stranded RNA . The multipartite genome is encapsidated , each segment in a separate nucleocapsid, and the nucleocapsids are surrounded by one envelope . The ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the subtypes of influenza A virus are estimated to have diverged 2,000 years ago. Metatranscriptomics studies have also identified closely related "influenza B-like" viruses such as the Wuhan spiny eel influenza virus and also "influenza B-like" viruses in a number of vertebrate species such as salamanders and fish. Diminishing the impact of this virus is the fact that, "in humans, influenza B viruses evolve slower than A viruses and faster than C viruses". Influenza B virus mutates at a rate 2 to 3 times slower than type A. In 1936, Thomas Francis Jr. discovered the ferret influenza B virus. Also in 1936, Macfarlane Burnet made the discovery that influenza virus may be cultured in hen embryonated eggs. This prompted research into the properties of the virus and the creation and application of inactivated vaccines in the late 1930s and early 1940s. Inactivated vaccines' usefulness as a preventative measure was proven in the 1950s. Later, 2003 saw the approval of the first live, attenuated influenza vaccine. Looking into influenza B specifically, Thomas Francis Jr. isolated influenza B virus in 1936. However, it was not until 1940 that influenza B viruses were discovered. In 1942, a new bivalent vaccine was developed that protected against both the H1N1 strain of influenza A and the newly discovered influenza B virus. In today's current world, even while some technology has advanced and flu vaccines now cover both strains of influenza A and B, the science is still based on findings from almost a century ago. The viruses included in flu vaccines are changed each year to match the strains of flu that are most likely to make people sick that year since flu viruses can develop swiftly and new mutations have appeared each year, like H1N1. Even though there have been two different lineages of influenza B viruses that were circulating during most seasons, flu vaccinations were long meant to protect against three different flu viruses: the influenza A(H1N1), influenza A( H3N2 ), and one type of influenza B virus. The second lineage of the B virus was since added to provide greater defense against circulating flu viruses. Two influenza A viruses and two influenza B viruses have up until 2023 been among the four flu viruses that a quadrivalent vaccine was intended to protect against. As of 2022 all flu vaccines in the United States were quadrivalent. The four main types of type A and B influenza viruses that are most likely to spread and make people sick during the upcoming flu season have been the targets of seasonal influenza (flu) vaccines. All of the available flu vaccinations in the United States have offered protection against the influenza A(H1), A(H3), B/Yamagata, and B/Victoria lineage viruses. Each of these four vaccine virus components has been chosen based on which flu viruses are infecting people ahead of the upcoming flu season, how widely they are spreading, how well the vaccines from the previous flu season may protect against those flu viruses, and the vaccine viruses' capacity to offer cross-protection. For the 2022–2023 flu season, there were three flu vaccines that were preferentially recommended for people 65 years and older; various influenza (flu) vaccinations are authorized for use in people of various age groups. In March 2022, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) convened in Silver Spring, Maryland, to choose the influenza viruses that would make up the influenza vaccine for the 2022–2023 influenza season in the United States. The committee proposed using A(H1N1)pdm09 , A(H3N2), and B/Austria/1359417/2021-like viruses for trivalent influenza vaccines to be utilized in the U.S. However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. In 1940, an acute respiratory illness outbreak in Northern America led to the discovery of influenza B virus (IBV), which was later discovered to not have any antigenic cross-reactivity with influenza A virus (IAV). Based on calculations of the rate of amino acid substitutions in HA proteins, it was estimated that IBV and IAV diverged from one another around 4000 years ago. However, the mechanisms of replication and transcription, as well as the functionality of the majority of viral proteins, appear to be largely conserved, with some unusual differences. Although IBV has occasionally been found in seals and pigs, its primary host species is the human. IBVs can also spread epidemics throughout the world, but they receive less attention than IAVs do due to their less prevalent nature, both in infecting hosts and in the symptoms that result from infection. IBVs used to be unclassified, but since the 1980s, they have been divided into the B/Yamagata and B/Victoria lineages. IBVs have further divisions known as clades and sub-clades, just like IAVs do. Hemagglutinin (HA) and neuraminidase (NA) are two virus surface antigens that are constantly changing. Antigenic drift or antigenic shift are two possible influenza viral changes. Small changes in the HA and NA of influenza viruses caused by antigenic drift result in the creation of novel strains that the immune system of humans might not be able to identify. These emerging strains are the influenza virus's evolutionary responses to a potent immunological response across the population. The main cause of influenza recurrence is antigenic drift, which makes it essential to reevaluate and update the influenza vaccine's ingredient list every year. Annual influenza outbreaks are caused by antigenic drift and declining immunity, when the residual defenses from prior exposures to related viruses are incomplete. Antigenic drift occurs in influenza A, B, and C. Hemagglutination inhibition experiments using ferret serum after infection allowed the identification of two very different antigenic influenza type B variants in the years 1988–1989. These viruses shared antigens with either B/Yamagata/16/88, a variation that was discovered in Japan in May 1988, or B/Victoria/2/87, the most recent reference strain. The B/Victoria/2/87 virus shared antigens with all influenza B viruses discovered in the United States during an outbreak in the winter of 1988–1989. In Japan, influenza B virus reinfection was investigated virologically in 1985–1991 and epidemiologically in 1979–1991 in children. Four influenza B virus outbreaks that each included antigenic drift occurred during the course of this study. Between the epidemics in 1987–1988 and 1989–1990, there was a significant genetic and antigenic change in the viruses. Depending on the influenza seasons, the minimum rate of reinfection with influenza B virus for the entire period was between 2 and 25%. Hemagglutination inhibition assays were used to examine the antigens of the influenza B virus primary and reinfection strains that were isolated from 18 children between the years of 1985 and 1990, which encompassed three epidemic periods. The findings revealed that reinfection occurred with the viruses recovered during the 1984–1985 and 1987–1988 influenza seasons, which belonged to the same lineage and were antigenically close. Today, the B/Yamagata lineage might be extinct as a result of COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. Although this development has resulted in updated recommendations regarding vaccine composition, continued surveillance is required to assess this conclusion fully, as pauses in IBV circulation have been observed before.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Bird/html

Bird

Birds are a group of warm-blooded vertebrates constituting the class Aves ( / ˈ eɪ v iː z / ), characterised by feathers , toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart , and a strong yet lightweight skeleton . Birds live worldwide and range in size from the 5.5 cm (2.2 in) bee hummingbird to the 2.8 m (9 ft 2 in) common ostrich . There are over 11,000 living species, more than half of which are passerine , or "perching" birds. Birds have wings whose development varies according to species; the only known groups without wings are the extinct moa and elephant birds . Wings, which are modified forelimbs , gave birds the ability to fly, although further evolution has led to the loss of flight in some birds , including ratites , penguins , and diverse endemic island species. The digestive and respiratory systems of birds are also uniquely adapted for flight. Some bird species of aquatic environments, particularly seabirds and some waterbirds , have further evolved for swimming. The study of birds is called ornithology . Birds are feathered theropod dinosaurs and constitute the only known living dinosaurs . Likewise, birds are considered reptiles in the modern cladistic sense of the term, and their closest living relatives are the crocodilians . Birds are descendants of the primitive avialans (whose members include Archaeopteryx ) which first appeared during the Late Jurassic . According to recent estimates, modern birds ( Neornithes ) evolved in the Late Cretaceous and diversified dramatically around the time of the Cretaceous–Paleogene extinction event 66 million years ago, which killed off the pterosaurs and all non-avian dinosaurs. Many social species pass on knowledge across generations, which is considered a form of culture . Birds are social, communicating with visual signals, calls, and songs , and participating in such behaviours as cooperative breeding and hunting, flocking , and mobbing of predators. The vast majority of bird species are socially (but not necessarily sexually) monogamous , usually for one breeding season at a time, sometimes for years, and rarely for life. Other species have breeding systems that are polygynous (one male with many females) or, rarely, polyandrous (one female with many males). Birds produce offspring by laying eggs which are fertilised through sexual reproduction . They are usually laid in a nest and incubated by the parents. Most birds have an extended period of parental care after hatching. Many species of birds are economically important as food for human consumption and raw material in manufacturing, with domesticated and undomesticated birds being important sources of eggs, meat, and feathers. Songbirds , parrots, and other species are popular as pets. Guano (bird excrement) is harvested for use as a fertiliser. Birds figure throughout human culture. About 120 to 130 species have become extinct due to human activity since the 17th century, and hundreds more before then. Human activity threatens about 1,200 bird species with extinction, though efforts are underway to protect them. Recreational birdwatching is an important part of the ecotourism industry.The first classification of birds was developed by Francis Willughby and John Ray in their 1676 volume Ornithologiae . Carl Linnaeus modified that work in 1758 to devise the taxonomic classification system currently in use. Birds are categorised as the biological class Aves in Linnaean taxonomy . Phylogenetic taxonomy places Aves in the clade Theropoda . Aves and a sister group, the order Crocodilia , contain the only living representatives of the reptile clade Archosauria . During the late 1990s, Aves was most commonly defined phylogenetically as all descendants of the most recent common ancestor of modern birds and Archaeopteryx lithographica . However, an earlier definition proposed by Jacques Gauthier gained wide currency in the 21st century, and is used by many scientists including adherents to the PhyloCode . Gauthier defined Aves to include only the crown group of the set of modern birds. This was done by excluding most groups known only from fossils , and assigning them, instead, to the broader group Avialae, on the principle that a clade based on extant species should be limited to those extant species and their closest extinct relatives. Gauthier and de Queiroz identified four different definitions for the same biological name "Aves", which is a problem. The authors proposed to reserve the term Aves only for the crown group consisting of the last common ancestor of all living birds and all of its descendants, which corresponds to meaning number 4 below. They assigned other names to the other groups. Lizards and snakes Turtles Crocodiles Birds Under the fourth definition Archaeopteryx , traditionally considered one of the earliest members of Aves, is removed from this group, becoming a non-avian dinosaur instead. These proposals have been adopted by many researchers in the field of palaeontology and bird evolution , though the exact definitions applied have been inconsistent. Avialae, initially proposed to replace the traditional fossil content of Aves, is often used synonymously with the vernacular term "bird" by these researchers. †Coelurus †Ornitholestes †Ornithomimosauria †Alvarezsauridae †Oviraptorosauria Paraves Most researchers define Avialae as branch-based clade, though definitions vary. Many authors have used a definition similar to "all theropods closer to birds than to Deinonychus ", with Troodon being sometimes added as a second external specifier in case it is closer to birds than to Deinonychus . Avialae is also occasionally defined as an apomorphy-based clade (that is, one based on physical characteristics). Jacques Gauthier , who named Avialae in 1986, re-defined it in 2001 as all dinosaurs that possessed feathered wings used in flapping flight , and the birds that descended from them. Despite being currently one of the most widely used, the crown-group definition of Aves has been criticised by some researchers. Lee and Spencer (1997) argued that, contrary to what Gauthier defended, this definition would not increase the stability of the clade and the exact content of Aves will always be uncertain because any defined clade (either crown or not) will have few synapomorphies distinguishing it from its closest relatives. Their alternative definition is synonymous to Avifilopluma. †Scansoriopterygidae †Eosinopteryx †Jinfengopteryx †Aurornis †Dromaeosauridae †Troodontidae Avialae Based on fossil and biological evidence, most scientists accept that birds are a specialised subgroup of theropod dinosaurs and, more specifically, members of Maniraptora , a group of theropods which includes dromaeosaurids and oviraptorosaurs , among others. As scientists have discovered more theropods closely related to birds, the previously clear distinction between non-birds and birds has become blurred. By the 2000s, discoveries in the Liaoning Province of northeast China, which demonstrated many small theropod feathered dinosaurs , contributed to this ambiguity. The consensus view in contemporary palaeontology is that the flying theropods, or avialans , are the closest relatives of the deinonychosaurs , which include dromaeosaurids and troodontids . Together, these form a group called Paraves . Some basal members of Deinonychosauria, such as Microraptor , have features which may have enabled them to glide or fly. The most basal deinonychosaurs were very small. This evidence raises the possibility that the ancestor of all paravians may have been arboreal , have been able to glide, or both. Unlike Archaeopteryx and the non-avialan feathered dinosaurs, who primarily ate meat, studies suggest that the first avialans were omnivores . The Late Jurassic Archaeopteryx is well known as one of the first transitional fossils to be found, and it provided support for the theory of evolution in the late 19th century. Archaeopteryx was the first fossil to display both clearly traditional reptilian characteristics—teeth, clawed fingers, and a long, lizard-like tail—as well as wings with flight feathers similar to those of modern birds. It is not considered a direct ancestor of birds, though it is possibly closely related to the true ancestor. Over 40% of key traits found in modern birds evolved during the 60 million year transition from the earliest bird-line archosaurs to the first maniraptoromorphs , i.e. the first dinosaurs closer to living birds than to Tyrannosaurus rex . The loss of osteoderms otherwise common in archosaurs and acquisition of primitive feathers might have occurred early during this phase. After the appearance of Maniraptoromorpha, the next 40 million years marked a continuous reduction of body size and the accumulation of neotenic (juvenile-like) characteristics. Hypercarnivory became increasingly less common while braincases enlarged and forelimbs became longer. The integument evolved into complex, pennaceous feathers . The oldest known paravian (and probably the earliest avialan) fossils come from the Tiaojishan Formation of China, which has been dated to the late Jurassic period ( Oxfordian stage), about 160 million years ago. The avialan species from this time period include Anchiornis huxleyi , Xiaotingia zhengi , and Aurornis xui . The well-known probable early avialan, Archaeopteryx , dates from slightly later Jurassic rocks (about 155 million years old) from Germany . Many of these early avialans shared unusual anatomical features that may be ancestral to modern birds but were later lost during bird evolution. These features include enlarged claws on the second toe which may have been held clear of the ground in life, and long feathers or "hind wings" covering the hind limbs and feet, which may have been used in aerial maneuvering. Avialans diversified into a wide variety of forms during the Cretaceous period. Many groups retained primitive characteristics , such as clawed wings and teeth, though the latter were lost independently in a number of avialan groups, including modern birds (Aves). Increasingly stiff tails (especially the outermost half) can be seen in the evolution of maniraptoromorphs, and this process culminated in the appearance of the pygostyle , an ossification of fused tail vertebrae. In the late Cretaceous, about 100 million years ago, the ancestors of all modern birds evolved a more open pelvis, allowing them to lay larger eggs compared to body size. Around 95 million years ago, they evolved a better sense of smell. A third stage of bird evolution starting with Ornithothoraces (the "bird-chested" avialans) can be associated with the refining of aerodynamics and flight capabilities, and the loss or co-ossification of several skeletal features. Particularly significant are the development of an enlarged, keeled sternum and the alula , and the loss of grasping hands. †Anchiornis †Archaeopteryx †Xiaotingia †Rahonavis †Jeholornis †Jixiangornis †Balaur †Zhongjianornis †Sapeornis †Confuciusornithiformes †Protopteryx †Pengornis Ornithothoraces †Enantiornithes †Archaeorhynchus †Patagopteryx †Vorona †Schizooura †Hongshanornithidae †Jianchangornis †Songlingornithidae †Gansus †Apsaravis †Hesperornithes †Ichthyornis †Vegavis Aves The first large, diverse lineage of short-tailed avialans to evolve were the Enantiornithes , or "opposite birds", so named because the construction of their shoulder bones was in reverse to that of modern birds. Enantiornithes occupied a wide array of ecological niches , from sand-probing shorebirds and fish-eaters to tree-dwelling forms and seed-eaters. While they were the dominant group of avialans during the Cretaceous period, enantiornithes became extinct along with many other dinosaur groups at the end of the Mesozoic era. Many species of the second major avialan lineage to diversify, the Euornithes (meaning "true birds", because they include the ancestors of modern birds), were semi-aquatic and specialised in eating fish and other small aquatic organisms. Unlike the Enantiornithes, which dominated land-based and arboreal habitats, most early euornithes lacked perching adaptations and likely included shorebird-like species, waders, and swimming and diving species. The latter included the superficially gull -like Ichthyornis and the Hesperornithiformes , which became so well adapted to hunting fish in marine environments that they lost the ability to fly and became primarily aquatic. The early euornithes also saw the development of many traits associated with modern birds, like strongly keeled breastbones, toothless, beaked portions of their jaws (though most non-avian euornithes retained teeth in other parts of the jaws). Euornithes also included the first avialans to develop true pygostyle and a fully mobile fan of tail feathers, which may have replaced the "hind wing" as the primary mode of aerial maneuverability and braking in flight. A study on mosaic evolution in the avian skull found that the last common ancestor of all Neornithes might have had a beak similar to that of the modern hook-billed vanga and a skull similar to that of the Eurasian golden oriole . As both species are small aerial and canopy foraging omnivores, a similar ecological niche was inferred for this hypothetical ancestor. ( ratites and tinamous ) ( landfowl and waterfowl ) (all other birds including perching birds) Most studies agree on a Cretaceous age for the most recent common ancestor of modern birds but estimates range from the Early Cretaceous to the latest Cretaceous. Similarly, there is no agreement on whether most of the early diversification of modern birds occurred in the Cretaceous and associated with breakup of the supercontinent Gondwana or occurred later and potentially as a consequence of the Cretaceous–Palaeogene extinction event . This disagreement is in part caused by a divergence in the evidence; most molecular dating studies suggests a Cretaceous evolutionary radiation , while fossil evidence points to a Cenozoic radiation (the so-called 'rocks' versus 'clocks' controversy). The discovery of Vegavis from the Maastrichtian , the last stage of the Late Cretaceous proved that the diversification of modern birds started before the Cenozoic era. The affinities of an earlier fossil, the possible galliform Austinornis lentus , dated to about 85 million years ago, are still too controversial to provide a fossil evidence of modern bird diversification. In 2020, Asteriornis from the Maastrichtian was described, it appears to be a close relative of Galloanserae , the earliest diverging lineage within Neognathae. Attempts to reconcile molecular and fossil evidence using genomic-scale DNA data and comprehensive fossil information have not resolved the controversy. However, a 2015 estimate that used a new method for calibrating molecular clocks confirmed that while modern birds originated early in the Late Cretaceous, likely in Western Gondwana , a pulse of diversification in all major groups occurred around the Cretaceous–Palaeogene extinction event. Modern birds would have expanded from West Gondwana through two routes. One route was an Antarctic interchange in the Paleogene. The other route was probably via Paleocene land bridges between South American and North America, which allowed for the rapid expansion and diversification of Neornithes into the Holarctic and Paleotropics . On the other hand, the occurrence of Asteriornis in the Northern Hemisphere suggest that Neornithes dispersed out of East Gondwana before the Paleocene. All modern birds lie within the crown group Aves (alternately Neornithes), which has two subdivisions: the Palaeognathae , which includes the flightless ratites (such as the ostriches ) and the weak-flying tinamous , and the extremely diverse Neognathae , containing all other birds. These two subdivisions have variously been given the rank of superorder , cohort, or infraclass. The number of known living bird species is around 11,000 although sources may differ in their precise numbers. Cladogram of modern bird relationships based on Stiller et al . (2024). Struthioniformes ( ostriches ) Tinamiformes (tinamous) Rheiformes (rheas) Apterygiformes (kiwis) Casuariiformes ( emu and cassowaries ) Galliformes ( chickens and relatives) Anseriformes ( ducks and relatives) Phoenicopteriformes ( flamingos ) Podicipediformes (grebes) Columbiformes (pigeons and doves) Mesitornithiformes (mesites) Pterocliformes (sandgrouse) Cuculiformes (cuckoos) Otidiformes (bustards) Musophagiformes (turacos) Opisthocomiformes (hoatzin) Gruiformes ( rails and cranes ) Charadriiformes ( waders and relatives) Caprimulgiformes (nightjars) Nyctibiiformes (potoos) Steatornithiformes (oilbird) Podargiformes (frogmouths) Aegotheliformes (owlet-nightjars) Apodiformes ( swifts , treeswifts and hummingbirds ) Phaethontiformes (tropicbirds) Eurypygiformes ( sunbittern and kagu ) Gaviiformes ( loons ) Procellariiformes ( albatrosses and petrels ) Sphenisciformes (penguins) Ciconiiformes (storks) Suliformes ( boobies , cormorants , etc.) Pelecaniformes ( pelicans , herons and ibises ) Strigiformes (owls) Cathartiformes (New World vultures) Accipitriformes ( hawks and relatives) Coliiformes (mousebirds) Leptosomiformes (cuckoo roller) Trogoniformes (trogons and quetzals) Bucerotiformes ( hornbills and relatives) Coraciiformes ( kingfishers and relatives) Piciformes ( woodpeckers and relatives) Cariamiformes (seriemas) Falconiformes (falcons) Psittaciformes (parrots) Passeriformes (passerines) The classification of birds is a contentious issue. Sibley and Ahlquist 's Phylogeny and Classification of Birds (1990) is a landmark work on the subject. Most evidence seems to suggest the assignment of orders is accurate, but scientists disagree about the relationships among the orders themselves; evidence from modern bird anatomy, fossils and DNA have all been brought to bear on the problem, but no strong consensus has emerged. Fossil and molecular evidence from the 2010s is providing an increasingly clear picture of the evolution of modern bird orders. As of 2010 [ update ] , the genome had been sequenced for only two birds, the chicken and the zebra finch . As of 2022 [ update ] the genomes of 542 species of birds had been completed. At least one genome has been sequenced from every order. These include at least one species in about 90% of extant avian families (218 out of 236 families recognised by the Howard and Moore Checklist ). Being able to sequence and compare whole genomes gives researchers many types of information, about genes, the DNA that regulates the genes, and their evolutionary history. This has led to reconsideration of some of the classifications that were based solely on the identification of protein-coding genes. Waterbirds such as pelicans and flamingos , for example, may have in common specific adaptations suited to their environment that were developed independently. Aves and a sister group, the order Crocodilia , contain the only living representatives of the reptile clade Archosauria . During the late 1990s, Aves was most commonly defined phylogenetically as all descendants of the most recent common ancestor of modern birds and Archaeopteryx lithographica . However, an earlier definition proposed by Jacques Gauthier gained wide currency in the 21st century, and is used by many scientists including adherents to the PhyloCode . Gauthier defined Aves to include only the crown group of the set of modern birds. This was done by excluding most groups known only from fossils , and assigning them, instead, to the broader group Avialae, on the principle that a clade based on extant species should be limited to those extant species and their closest extinct relatives. Gauthier and de Queiroz identified four different definitions for the same biological name "Aves", which is a problem. The authors proposed to reserve the term Aves only for the crown group consisting of the last common ancestor of all living birds and all of its descendants, which corresponds to meaning number 4 below. They assigned other names to the other groups. Lizards and snakes Turtles Crocodiles Birds Under the fourth definition Archaeopteryx , traditionally considered one of the earliest members of Aves, is removed from this group, becoming a non-avian dinosaur instead. These proposals have been adopted by many researchers in the field of palaeontology and bird evolution , though the exact definitions applied have been inconsistent. Avialae, initially proposed to replace the traditional fossil content of Aves, is often used synonymously with the vernacular term "bird" by these researchers. †Coelurus †Ornitholestes †Ornithomimosauria †Alvarezsauridae †Oviraptorosauria Paraves Most researchers define Avialae as branch-based clade, though definitions vary. Many authors have used a definition similar to "all theropods closer to birds than to Deinonychus ", with Troodon being sometimes added as a second external specifier in case it is closer to birds than to Deinonychus . Avialae is also occasionally defined as an apomorphy-based clade (that is, one based on physical characteristics). Jacques Gauthier , who named Avialae in 1986, re-defined it in 2001 as all dinosaurs that possessed feathered wings used in flapping flight , and the birds that descended from them. Despite being currently one of the most widely used, the crown-group definition of Aves has been criticised by some researchers. Lee and Spencer (1997) argued that, contrary to what Gauthier defended, this definition would not increase the stability of the clade and the exact content of Aves will always be uncertain because any defined clade (either crown or not) will have few synapomorphies distinguishing it from its closest relatives. Their alternative definition is synonymous to Avifilopluma. †Scansoriopterygidae †Eosinopteryx †Jinfengopteryx †Aurornis †Dromaeosauridae †Troodontidae Avialae Based on fossil and biological evidence, most scientists accept that birds are a specialised subgroup of theropod dinosaurs and, more specifically, members of Maniraptora , a group of theropods which includes dromaeosaurids and oviraptorosaurs , among others. As scientists have discovered more theropods closely related to birds, the previously clear distinction between non-birds and birds has become blurred. By the 2000s, discoveries in the Liaoning Province of northeast China, which demonstrated many small theropod feathered dinosaurs , contributed to this ambiguity. The consensus view in contemporary palaeontology is that the flying theropods, or avialans , are the closest relatives of the deinonychosaurs , which include dromaeosaurids and troodontids . Together, these form a group called Paraves . Some basal members of Deinonychosauria, such as Microraptor , have features which may have enabled them to glide or fly. The most basal deinonychosaurs were very small. This evidence raises the possibility that the ancestor of all paravians may have been arboreal , have been able to glide, or both. Unlike Archaeopteryx and the non-avialan feathered dinosaurs, who primarily ate meat, studies suggest that the first avialans were omnivores . The Late Jurassic Archaeopteryx is well known as one of the first transitional fossils to be found, and it provided support for the theory of evolution in the late 19th century. Archaeopteryx was the first fossil to display both clearly traditional reptilian characteristics—teeth, clawed fingers, and a long, lizard-like tail—as well as wings with flight feathers similar to those of modern birds. It is not considered a direct ancestor of birds, though it is possibly closely related to the true ancestor. Over 40% of key traits found in modern birds evolved during the 60 million year transition from the earliest bird-line archosaurs to the first maniraptoromorphs , i.e. the first dinosaurs closer to living birds than to Tyrannosaurus rex . The loss of osteoderms otherwise common in archosaurs and acquisition of primitive feathers might have occurred early during this phase. After the appearance of Maniraptoromorpha, the next 40 million years marked a continuous reduction of body size and the accumulation of neotenic (juvenile-like) characteristics. Hypercarnivory became increasingly less common while braincases enlarged and forelimbs became longer. The integument evolved into complex, pennaceous feathers . The oldest known paravian (and probably the earliest avialan) fossils come from the Tiaojishan Formation of China, which has been dated to the late Jurassic period ( Oxfordian stage), about 160 million years ago. The avialan species from this time period include Anchiornis huxleyi , Xiaotingia zhengi , and Aurornis xui . The well-known probable early avialan, Archaeopteryx , dates from slightly later Jurassic rocks (about 155 million years old) from Germany . Many of these early avialans shared unusual anatomical features that may be ancestral to modern birds but were later lost during bird evolution. These features include enlarged claws on the second toe which may have been held clear of the ground in life, and long feathers or "hind wings" covering the hind limbs and feet, which may have been used in aerial maneuvering. Avialans diversified into a wide variety of forms during the Cretaceous period. Many groups retained primitive characteristics , such as clawed wings and teeth, though the latter were lost independently in a number of avialan groups, including modern birds (Aves). Increasingly stiff tails (especially the outermost half) can be seen in the evolution of maniraptoromorphs, and this process culminated in the appearance of the pygostyle , an ossification of fused tail vertebrae. In the late Cretaceous, about 100 million years ago, the ancestors of all modern birds evolved a more open pelvis, allowing them to lay larger eggs compared to body size. Around 95 million years ago, they evolved a better sense of smell. A third stage of bird evolution starting with Ornithothoraces (the "bird-chested" avialans) can be associated with the refining of aerodynamics and flight capabilities, and the loss or co-ossification of several skeletal features. Particularly significant are the development of an enlarged, keeled sternum and the alula , and the loss of grasping hands. †Anchiornis †Archaeopteryx †Xiaotingia †Rahonavis †Jeholornis †Jixiangornis †Balaur †Zhongjianornis †Sapeornis †Confuciusornithiformes †Protopteryx †Pengornis Ornithothoraces†Enantiornithes †Archaeorhynchus †Patagopteryx †Vorona †Schizooura †Hongshanornithidae †Jianchangornis †Songlingornithidae †Gansus †Apsaravis †Hesperornithes †Ichthyornis †Vegavis Aves The first large, diverse lineage of short-tailed avialans to evolve were the Enantiornithes , or "opposite birds", so named because the construction of their shoulder bones was in reverse to that of modern birds. Enantiornithes occupied a wide array of ecological niches , from sand-probing shorebirds and fish-eaters to tree-dwelling forms and seed-eaters. While they were the dominant group of avialans during the Cretaceous period, enantiornithes became extinct along with many other dinosaur groups at the end of the Mesozoic era. Many species of the second major avialan lineage to diversify, the Euornithes (meaning "true birds", because they include the ancestors of modern birds), were semi-aquatic and specialised in eating fish and other small aquatic organisms. Unlike the Enantiornithes, which dominated land-based and arboreal habitats, most early euornithes lacked perching adaptations and likely included shorebird-like species, waders, and swimming and diving species. The latter included the superficially gull -like Ichthyornis and the Hesperornithiformes , which became so well adapted to hunting fish in marine environments that they lost the ability to fly and became primarily aquatic. The early euornithes also saw the development of many traits associated with modern birds, like strongly keeled breastbones, toothless, beaked portions of their jaws (though most non-avian euornithes retained teeth in other parts of the jaws). Euornithes also included the first avialans to develop true pygostyle and a fully mobile fan of tail feathers, which may have replaced the "hind wing" as the primary mode of aerial maneuverability and braking in flight. A study on mosaic evolution in the avian skull found that the last common ancestor of all Neornithes might have had a beak similar to that of the modern hook-billed vanga and a skull similar to that of the Eurasian golden oriole . As both species are small aerial and canopy foraging omnivores, a similar ecological niche was inferred for this hypothetical ancestor. ( ratites and tinamous ) ( landfowl and waterfowl ) (all other birds including perching birds) Most studies agree on a Cretaceous age for the most recent common ancestor of modern birds but estimates range from the Early Cretaceous to the latest Cretaceous. Similarly, there is no agreement on whether most of the early diversification of modern birds occurred in the Cretaceous and associated with breakup of the supercontinent Gondwana or occurred later and potentially as a consequence of the Cretaceous–Palaeogene extinction event . This disagreement is in part caused by a divergence in the evidence; most molecular dating studies suggests a Cretaceous evolutionary radiation , while fossil evidence points to a Cenozoic radiation (the so-called 'rocks' versus 'clocks' controversy). The discovery of Vegavis from the Maastrichtian , the last stage of the Late Cretaceous proved that the diversification of modern birds started before the Cenozoic era. The affinities of an earlier fossil, the possible galliform Austinornis lentus , dated to about 85 million years ago, are still too controversial to provide a fossil evidence of modern bird diversification. In 2020, Asteriornis from the Maastrichtian was described, it appears to be a close relative of Galloanserae , the earliest diverging lineage within Neognathae. Attempts to reconcile molecular and fossil evidence using genomic-scale DNA data and comprehensive fossil information have not resolved the controversy. However, a 2015 estimate that used a new method for calibrating molecular clocks confirmed that while modern birds originated early in the Late Cretaceous, likely in Western Gondwana , a pulse of diversification in all major groups occurred around the Cretaceous–Palaeogene extinction event. Modern birds would have expanded from West Gondwana through two routes. One route was an Antarctic interchange in the Paleogene. The other route was probably via Paleocene land bridges between South American and North America, which allowed for the rapid expansion and diversification of Neornithes into the Holarctic and Paleotropics . On the other hand, the occurrence of Asteriornis in the Northern Hemisphere suggest that Neornithes dispersed out of East Gondwana before the Paleocene. All modern birds lie within the crown group Aves (alternately Neornithes), which has two subdivisions: the Palaeognathae , which includes the flightless ratites (such as the ostriches ) and the weak-flying tinamous , and the extremely diverse Neognathae , containing all other birds. These two subdivisions have variously been given the rank of superorder , cohort, or infraclass. The number of known living bird species is around 11,000 although sources may differ in their precise numbers. Cladogram of modern bird relationships based on Stiller et al . (2024). Struthioniformes ( ostriches ) Tinamiformes (tinamous) Rheiformes (rheas) Apterygiformes (kiwis) Casuariiformes ( emu and cassowaries ) Galliformes ( chickens and relatives) Anseriformes ( ducks and relatives) Phoenicopteriformes ( flamingos ) Podicipediformes (grebes) Columbiformes (pigeons and doves) Mesitornithiformes (mesites) Pterocliformes (sandgrouse) Cuculiformes (cuckoos) Otidiformes (bustards) Musophagiformes (turacos) Opisthocomiformes (hoatzin) Gruiformes ( rails and cranes ) Charadriiformes ( waders and relatives) Caprimulgiformes (nightjars) Nyctibiiformes (potoos) Steatornithiformes (oilbird) Podargiformes (frogmouths) Aegotheliformes (owlet-nightjars) Apodiformes ( swifts , treeswifts and hummingbirds ) Phaethontiformes (tropicbirds) Eurypygiformes ( sunbittern and kagu ) Gaviiformes ( loons ) Procellariiformes ( albatrosses and petrels ) Sphenisciformes (penguins) Ciconiiformes (storks) Suliformes ( boobies , cormorants , etc.) Pelecaniformes ( pelicans , herons and ibises ) Strigiformes (owls) Cathartiformes (New World vultures) Accipitriformes ( hawks and relatives) Coliiformes (mousebirds) Leptosomiformes (cuckoo roller) Trogoniformes (trogons and quetzals) Bucerotiformes ( hornbills and relatives) Coraciiformes ( kingfishers and relatives) Piciformes ( woodpeckers and relatives) Cariamiformes (seriemas) Falconiformes (falcons) Psittaciformes (parrots) Passeriformes (passerines) The classification of birds is a contentious issue. Sibley and Ahlquist 's Phylogeny and Classification of Birds (1990) is a landmark work on the subject. Most evidence seems to suggest the assignment of orders is accurate, but scientists disagree about the relationships among the orders themselves; evidence from modern bird anatomy, fossils and DNA have all been brought to bear on the problem, but no strong consensus has emerged. Fossil and molecular evidence from the 2010s is providing an increasingly clear picture of the evolution of modern bird orders. As of 2010 [ update ] , the genome had been sequenced for only two birds, the chicken and the zebra finch . As of 2022 [ update ] the genomes of 542 species of birds had been completed. At least one genome has been sequenced from every order. These include at least one species in about 90% of extant avian families (218 out of 236 families recognised by the Howard and Moore Checklist ). Being able to sequence and compare whole genomes gives researchers many types of information, about genes, the DNA that regulates the genes, and their evolutionary history. This has led to reconsideration of some of the classifications that were based solely on the identification of protein-coding genes. Waterbirds such as pelicans and flamingos , for example, may have in common specific adaptations suited to their environment that were developed independently. Birds live and breed in most terrestrial habitats and on all seven continents, reaching their southern extreme in the snow petrel 's breeding colonies up to 440 kilometres (270 mi) inland in Antarctica . The highest bird diversity occurs in tropical regions. It was earlier thought that this high diversity was the result of higher speciation rates in the tropics; however studies from the 2000s found higher speciation rates in the high latitudes that were offset by greater extinction rates than in the tropics. Many species migrate annually over great distances and across oceans; several families of birds have adapted to life both on the world's oceans and in them, and some seabird species come ashore only to breed, while some penguins have been recorded diving up to 300 metres (980 ft) deep. Many bird species have established breeding populations in areas to which they have been introduced by humans. Some of these introductions have been deliberate; the ring-necked pheasant , for example, has been introduced around the world as a game bird . Others have been accidental, such as the establishment of wild monk parakeets in several North American cities after their escape from captivity. Some species, including cattle egret , yellow-headed caracara and galah , have spread naturally far beyond their original ranges as agricultural expansion created alternative habitats although modern practices of intensive agriculture have negatively impacted farmland bird populations. Compared with other vertebrates, birds have a body plan that shows many unusual adaptations, mostly to facilitate flight . The skeleton consists of very lightweight bones. They have large air-filled cavities (called pneumatic cavities) which connect with the respiratory system . The skull bones in adults are fused and do not show cranial sutures . The orbital cavities that house the eyeballs are large and separated from each other by a bony septum (partition). The spine has cervical, thoracic, lumbar and caudal regions with the number of cervical (neck) vertebrae highly variable and especially flexible, but movement is reduced in the anterior thoracic vertebrae and absent in the later vertebrae. The last few are fused with the pelvis to form the synsacrum . The ribs are flattened and the sternum is keeled for the attachment of flight muscles except in the flightless bird orders. The forelimbs are modified into wings. The wings are more or less developed depending on the species; the only known groups that lost their wings are the extinct moa and elephant birds . Like the reptiles , birds are primarily uricotelic , that is, their kidneys extract nitrogenous waste from their bloodstream and excrete it as uric acid , instead of urea or ammonia , through the ureters into the intestine. Birds do not have a urinary bladder or external urethral opening and (with exception of the ostrich ) uric acid is excreted along with faeces as a semisolid waste. However, birds such as hummingbirds can be facultatively ammonotelic, excreting most of the nitrogenous wastes as ammonia. They also excrete creatine , rather than creatinine like mammals. This material, as well as the output of the intestines, emerges from the bird's cloaca . The cloaca is a multi-purpose opening: waste is expelled through it, most birds mate by joining cloaca , and females lay eggs from it. In addition, many species of birds regurgitate pellets . It is a common but not universal feature of altricial passerine nestlings (born helpless, under constant parental care) that instead of excreting directly into the nest, they produce a fecal sac . This is a mucus-covered pouch that allows parents to either dispose of the waste outside the nest or to recycle the waste through their own digestive system. Males within Palaeognathae (with the exception of the kiwis ), the Anseriformes (with the exception of screamers ), and in rudimentary forms in Galliformes (but fully developed in Cracidae ) possess a penis , which is never present in Neoaves . The length is thought to be related to sperm competition . For male birds to get an erection, they depend on lymphatic fluid instead of blood. When not copulating, it is hidden within the proctodeum compartment within the cloaca, just inside the vent. Female birds have sperm storage tubules that allow sperm to remain viable long after copulation, a hundred days in some species. Sperm from multiple males may compete through this mechanism. Most female birds have a single ovary and a single oviduct , both on the left side, but there are exceptions: species in at least 16 different orders of birds have two ovaries. Even these species, however, tend to have a single oviduct. It has been speculated that this might be an adaptation to flight, but males have two testes, and it is also observed that the gonads in both sexes decrease dramatically in size outside the breeding season. Also terrestrial birds generally have a single ovary, as does the platypus , an egg-laying mammal. A more likely explanation is that the egg develops a shell while passing through the oviduct over a period of about a day, so that if two eggs were to develop at the same time, there would be a risk to survival. While rare, mostly abortive, parthenogenesis is not unknown in birds and eggs can be diploid , automictic and results in male offspring. Birds are solely gonochoric . Meaning they have two sexes: either female or male . The sex of birds is determined by the Z and W sex chromosomes , rather than by the X and Y chromosomes present in mammals . Male birds have two Z chromosomes (ZZ), and female birds have a W chromosome and a Z chromosome (WZ). A complex system of disassortative mating with two morphs is involved in the white-throated sparrow Zonotrichia albicollis , where white- and tan-browed morphs of opposite sex pair, making it appear as if four sexes were involved since any individual is compatible with only a fourth of the population. In nearly all species of birds, an individual's sex is determined at fertilisation. However, one 2007 study claimed to demonstrate temperature-dependent sex determination among the Australian brushturkey , for which higher temperatures during incubation resulted in a higher female-to-male sex ratio . This, however, was later proven to not be the case. These birds do not exhibit temperature-dependent sex determination, but temperature-dependent sex mortality. Birds have one of the most complex respiratory systems of all animal groups. Upon inhalation, 75% of the fresh air bypasses the lungs and flows directly into a posterior air sac which extends from the lungs and connects with air spaces in the bones and fills them with air. The other 25% of the air goes directly into the lungs. When the bird exhales, the used air flows out of the lungs and the stored fresh air from the posterior air sac is simultaneously forced into the lungs. Thus, a bird's lungs receive a constant supply of fresh air during both inhalation and exhalation. Sound production is achieved using the syrinx , a muscular chamber incorporating multiple tympanic membranes which diverges from the lower end of the trachea; the trachea being elongated in some species, increasing the volume of vocalisations and the perception of the bird's size. In birds, the main arteries taking blood away from the heart originate from the right aortic arch (or pharyngeal arch), unlike in the mammals where the left aortic arch forms this part of the aorta . The postcava receives blood from the limbs via the renal portal system. Unlike in mammals, the circulating red blood cells in birds retain their nucleus . The avian circulatory system is driven by a four-chambered, myogenic heart contained in a fibrous pericardial sac. This pericardial sac is filled with a serous fluid for lubrication. The heart itself is divided into a right and left half, each with an atrium and ventricle . The atrium and ventricles of each side are separated by atrioventricular valves which prevent back flow from one chamber to the next during contraction. Being myogenic, the heart's pace is maintained by pacemaker cells found in the sinoatrial node, located on the right atrium. The sinoatrial node uses calcium to cause a depolarising signal transduction pathway from the atrium through right and left atrioventricular bundle which communicates contraction to the ventricles. The avian heart also consists of muscular arches that are made up of thick bundles of muscular layers. Much like a mammalian heart, the avian heart is composed of endocardial , myocardial and epicardial layers. The atrium walls tend to be thinner than the ventricle walls, due to the intense ventricular contraction used to pump oxygenated blood throughout the body. Avian hearts are generally larger than mammalian hearts when compared to body mass. This adaptation allows more blood to be pumped to meet the high metabolic need associated with flight. Birds have a very efficient system for diffusing oxygen into the blood; birds have a ten times greater surface area to gas exchange volume than mammals. As a result, birds have more blood in their capillaries per unit of volume of lung than a mammal. The arteries are composed of thick elastic muscles to withstand the pressure of the ventricular contractions, and become more rigid as they move away from the heart. Blood moves through the arteries, which undergo vasoconstriction , and into arterioles which act as a transportation system to distribute primarily oxygen as well as nutrients to all tissues of the body. As the arterioles move away from the heart and into individual organs and tissues they are further divided to increase surface area and slow blood flow. Blood travels through the arterioles and moves into the capillaries where gas exchange can occur. [ citation needed ] Capillaries are organised into capillary beds in tissues; it is here that blood exchanges oxygen for carbon dioxide waste. In the capillary beds, blood flow is slowed to allow maximum diffusion of oxygen into the tissues. Once the blood has become deoxygenated, it travels through venules then veins and back to the heart. Veins, unlike arteries, are thin and rigid as they do not need to withstand extreme pressure. As blood travels through the venules to the veins a funneling occurs called vasodilation bringing blood back to the heart. Once the blood reaches the heart, it moves first into the right atrium, then the right ventricle to be pumped through the lungs for further gas exchange of carbon dioxide waste for oxygen. Oxygenated blood then flows from the lungs through the left atrium to the left ventricle where it is pumped out to the body. [ citation needed ] The nervous system is large relative to the bird's size. The most developed part of the brain of birds is the one that controls the flight-related functions, while the cerebellum coordinates movement and the cerebrum controls behaviour patterns, navigation, mating and nest building. Most birds have a poor sense of smell with notable exceptions including kiwis , New World vultures and tubenoses . The avian visual system is usually highly developed. Water birds have special flexible lenses, allowing accommodation for vision in air and water. Some species also have dual fovea . Birds are tetrachromatic , possessing ultraviolet (UV) sensitive cone cells in the eye as well as green, red and blue ones. They also have double cones , likely to mediate achromatic vision . Many birds show plumage patterns in ultraviolet that are invisible to the human eye; some birds whose sexes appear similar to the naked eye are distinguished by the presence of ultraviolet reflective patches on their feathers. Male blue tits have an ultraviolet reflective crown patch which is displayed in courtship by posturing and raising of their nape feathers. Ultraviolet light is also used in foraging— kestrels have been shown to search for prey by detecting the UV reflective urine trail marks left on the ground by rodents. With the exception of pigeons and a few other species, the eyelids of birds are not used in blinking. Instead the eye is lubricated by the nictitating membrane , a third eyelid that moves horizontally. The nictitating membrane also covers the eye and acts as a contact lens in many aquatic birds. The bird retina has a fan shaped blood supply system called the pecten . Eyes of most birds are large, not very round and capable of only limited movement in the orbits, typically 10–20°. Birds with eyes on the sides of their heads have a wide visual field , while birds with eyes on the front of their heads, such as owls, have binocular vision and can estimate the depth of field . The avian ear lacks external pinnae but is covered by feathers, although in some birds, such as the Asio , Bubo and Otus owls , these feathers form tufts which resemble ears. The inner ear has a cochlea , but it is not spiral as in mammals. A few species are able to use chemical defences against predators; some Procellariiformes can eject an unpleasant stomach oil against an aggressor, and some species of pitohuis from New Guinea have a powerful neurotoxin in their skin and feathers. A lack of field observations limit our knowledge, but intraspecific conflicts are known to sometimes result in injury or death. The screamers ( Anhimidae ), some jacanas ( Jacana , Hydrophasianus ), the spur-winged goose ( Plectropterus ), the torrent duck ( Merganetta ) and nine species of lapwing ( Vanellus ) use a sharp spur on the wing as a weapon. The steamer ducks ( Tachyeres ), geese and swans ( Anserinae ), the solitaire ( Pezophaps ), sheathbills ( Chionis ), some guans ( Crax ) and stone curlews ( Burhinus ) use a bony knob on the alular metacarpal to punch and hammer opponents. The jacanas Actophilornis and Irediparra have an expanded, blade-like radius. The extinct Xenicibis was unique in having an elongate forelimb and massive hand which likely functioned in combat or defence as a jointed club or flail. Swans , for instance, may strike with the bony spurs and bite when defending eggs or young. Feathers are a feature characteristic of birds (though also present in some dinosaurs not currently considered to be true birds). They facilitate flight , provide insulation that aids in thermoregulation , and are used in display, camouflage, and signalling. There are several types of feathers, each serving its own set of purposes. Feathers are epidermal growths attached to the skin and arise only in specific tracts of skin called pterylae . The distribution pattern of these feather tracts (pterylosis) is used in taxonomy and systematics. The arrangement and appearance of feathers on the body, called plumage , may vary within species by age, social status , and sex . Plumage is regularly moulted ; the standard plumage of a bird that has moulted after breeding is known as the " non-breeding " plumage, or—in the Humphrey–Parkes terminology —"basic" plumage; breeding plumages or variations of the basic plumage are known under the Humphrey–Parkes system as " alternate " plumages. Moulting is annual in most species, although some may have two moults a year, and large birds of prey may moult only once every few years. Moulting patterns vary across species. In passerines, flight feathers are replaced one at a time with the innermost primary being the first. When the fifth of sixth primary is replaced, the outermost tertiaries begin to drop. After the innermost tertiaries are moulted, the secondaries starting from the innermost begin to drop and this proceeds to the outer feathers (centrifugal moult). The greater primary coverts are moulted in synchrony with the primary that they overlap. A small number of species, such as ducks and geese, lose all of their flight feathers at once, temporarily becoming flightless. As a general rule, the tail feathers are moulted and replaced starting with the innermost pair. Centripetal moults of tail feathers are however seen in the Phasianidae . The centrifugal moult is modified in the tail feathers of woodpeckers and treecreepers , in that it begins with the second innermost pair of feathers and finishes with the central pair of feathers so that the bird maintains a functional climbing tail. The general pattern seen in passerines is that the primaries are replaced outward, secondaries inward, and the tail from centre outward. Before nesting, the females of most bird species gain a bare brood patch by losing feathers close to the belly. The skin there is well supplied with blood vessels and helps the bird in incubation. Feathers require maintenance and birds preen or groom them daily, spending an average of around 9% of their daily time on this. The bill is used to brush away foreign particles and to apply waxy secretions from the uropygial gland ; these secretions protect the feathers' flexibility and act as an antimicrobial agent , inhibiting the growth of feather-degrading bacteria . This may be supplemented with the secretions of formic acid from ants, which birds receive through a behaviour known as anting , to remove feather parasites. The scales of birds are composed of the same keratin as beaks, claws, and spurs. They are found mainly on the toes and metatarsus , but may be found further up on the ankle in some birds. Most bird scales do not overlap significantly, except in the cases of kingfishers and woodpeckers . The scales of birds are thought to be homologous to those of reptiles and mammals. Most birds can fly , which distinguishes them from almost all other vertebrate classes. Flight is the primary means of locomotion for most bird species and is used for searching for food and for escaping from predators. Birds have various adaptations for flight, including a lightweight skeleton, two large flight muscles, the pectoralis (which accounts for 15% of the total mass of the bird) and the supracoracoideus, as well as a modified forelimb ( wing ) that serves as an aerofoil . Wing shape and size generally determine a bird's flight style and performance; many birds combine powered, flapping flight with less energy-intensive soaring flight. About 60 extant bird species are flightless , as were many extinct birds. Flightlessness often arises in birds on isolated islands, most likely due to limited resources and the absence of mammalian land predators. Flightlessness is almost exclusively correlated with gigantism due to an island's inherent condition of isolation. Although flightless, penguins use similar musculature and movements to "fly" through the water, as do some flight-capable birds such as auks , shearwaters and dippers . The skeleton consists of very lightweight bones. They have large air-filled cavities (called pneumatic cavities) which connect with the respiratory system . The skull bones in adults are fused and do not show cranial sutures . The orbital cavities that house the eyeballs are large and separated from each other by a bony septum (partition). The spine has cervical, thoracic, lumbar and caudal regions with the number of cervical (neck) vertebrae highly variable and especially flexible, but movement is reduced in the anterior thoracic vertebrae and absent in the later vertebrae. The last few are fused with the pelvis to form the synsacrum . The ribs are flattened and the sternum is keeled for the attachment of flight muscles except in the flightless bird orders. The forelimbs are modified into wings. The wings are more or less developed depending on the species; the only known groups that lost their wings are the extinct moa and elephant birds . Like the reptiles , birds are primarily uricotelic , that is, their kidneys extract nitrogenous waste from their bloodstream and excrete it as uric acid , instead of urea or ammonia , through the ureters into the intestine. Birds do not have a urinary bladder or external urethral opening and (with exception of the ostrich ) uric acid is excreted along with faeces as a semisolid waste. However, birds such as hummingbirds can be facultatively ammonotelic, excreting most of the nitrogenous wastes as ammonia. They also excrete creatine , rather than creatinine like mammals. This material, as well as the output of the intestines, emerges from the bird's cloaca . The cloaca is a multi-purpose opening: waste is expelled through it, most birds mate by joining cloaca , and females lay eggs from it. In addition, many species of birds regurgitate pellets . It is a common but not universal feature of altricial passerine nestlings (born helpless, under constant parental care) that instead of excreting directly into the nest, they produce a fecal sac . This is a mucus-covered pouch that allows parents to either dispose of the waste outside the nest or to recycle the waste through their own digestive system. Males within Palaeognathae (with the exception of the kiwis ), the Anseriformes (with the exception of screamers ), and in rudimentary forms in Galliformes (but fully developed in Cracidae ) possess a penis , which is never present in Neoaves . The length is thought to be related to sperm competition . For male birds to get an erection, they depend on lymphatic fluid instead of blood. When not copulating, it is hidden within the proctodeum compartment within the cloaca, just inside the vent. Female birds have sperm storage tubules that allow sperm to remain viable long after copulation, a hundred days in some species. Sperm from multiple males may compete through this mechanism. Most female birds have a single ovary and a single oviduct , both on the left side, but there are exceptions: species in at least 16 different orders of birds have two ovaries. Even these species, however, tend to have a single oviduct. It has been speculated that this might be an adaptation to flight, but males have two testes, and it is also observed that the gonads in both sexes decrease dramatically in size outside the breeding season. Also terrestrial birds generally have a single ovary, as does the platypus , an egg-laying mammal. A more likely explanation is that the egg develops a shell while passing through the oviduct over a period of about a day, so that if two eggs were to develop at the same time, there would be a risk to survival. While rare, mostly abortive, parthenogenesis is not unknown in birds and eggs can be diploid , automictic and results in male offspring. Birds are solely gonochoric . Meaning they have two sexes: either female or male . The sex of birds is determined by the Z and W sex chromosomes , rather than by the X and Y chromosomes present in mammals . Male birds have two Z chromosomes (ZZ), and female birds have a W chromosome and a Z chromosome (WZ). A complex system of disassortative mating with two morphs is involved in the white-throated sparrow Zonotrichia albicollis , where white- and tan-browed morphs of opposite sex pair, making it appear as if four sexes were involved since any individual is compatible with only a fourth of the population. In nearly all species of birds, an individual's sex is determined at fertilisation. However, one 2007 study claimed to demonstrate temperature-dependent sex determination among the Australian brushturkey , for which higher temperatures during incubation resulted in a higher female-to-male sex ratio . This, however, was later proven to not be the case. These birds do not exhibit temperature-dependent sex determination, but temperature-dependent sex mortality. Birds have one of the most complex respiratory systems of all animal groups. Upon inhalation, 75% of the fresh air bypasses the lungs and flows directly into a posterior air sac which extends from the lungs and connects with air spaces in the bones and fills them with air. The other 25% of the air goes directly into the lungs. When the bird exhales, the used air flows out of the lungs and the stored fresh air from the posterior air sac is simultaneously forced into the lungs. Thus, a bird's lungs receive a constant supply of fresh air during both inhalation and exhalation. Sound production is achieved using the syrinx , a muscular chamber incorporating multiple tympanic membranes which diverges from the lower end of the trachea; the trachea being elongated in some species, increasing the volume of vocalisations and the perception of the bird's size. In birds, the main arteries taking blood away from the heart originate from the right aortic arch (or pharyngeal arch), unlike in the mammals where the left aortic arch forms this part of the aorta . The postcava receives blood from the limbs via the renal portal system. Unlike in mammals, the circulating red blood cells in birds retain their nucleus . The avian circulatory system is driven by a four-chambered, myogenic heart contained in a fibrous pericardial sac. This pericardial sac is filled with a serous fluid for lubrication. The heart itself is divided into a right and left half, each with an atrium and ventricle . The atrium and ventricles of each side are separated by atrioventricular valves which prevent back flow from one chamber to the next during contraction. Being myogenic, the heart's pace is maintained by pacemaker cells found in the sinoatrial node, located on the right atrium. The sinoatrial node uses calcium to cause a depolarising signal transduction pathway from the atrium through right and left atrioventricular bundle which communicates contraction to the ventricles. The avian heart also consists of muscular arches that are made up of thick bundles of muscular layers. Much like a mammalian heart, the avian heart is composed of endocardial , myocardial and epicardial layers. The atrium walls tend to be thinner than the ventricle walls, due to the intense ventricular contraction used to pump oxygenated blood throughout the body. Avian hearts are generally larger than mammalian hearts when compared to body mass. This adaptation allows more blood to be pumped to meet the high metabolic need associated with flight. Birds have a very efficient system for diffusing oxygen into the blood; birds have a ten times greater surface area to gas exchange volume than mammals. As a result, birds have more blood in their capillaries per unit of volume of lung than a mammal. The arteries are composed of thick elastic muscles to withstand the pressure of the ventricular contractions, and become more rigid as they move away from the heart. Blood moves through the arteries, which undergo vasoconstriction , and into arterioles which act as a transportation system to distribute primarily oxygen as well as nutrients to all tissues of the body. As the arterioles move away from the heart and into individual organs and tissues they are further divided to increase surface area and slow blood flow. Blood travels through the arterioles and moves into the capillaries where gas exchange can occur. [ citation needed ] Capillaries are organised into capillary beds in tissues; it is here that blood exchanges oxygen for carbon dioxide waste. In the capillary beds, blood flow is slowed to allow maximum diffusion of oxygen into the tissues. Once the blood has become deoxygenated, it travels through venules then veins and back to the heart. Veins, unlike arteries, are thin and rigid as they do not need to withstand extreme pressure. As blood travels through the venules to the veins a funneling occurs called vasodilation bringing blood back to the heart. Once the blood reaches the heart, it moves first into the right atrium, then the right ventricle to be pumped through the lungs for further gas exchange of carbon dioxide waste for oxygen. Oxygenated blood then flows from the lungs through the left atrium to the left ventricle where it is pumped out to the body. [ citation needed ]The avian circulatory system is driven by a four-chambered, myogenic heart contained in a fibrous pericardial sac. This pericardial sac is filled with a serous fluid for lubrication. The heart itself is divided into a right and left half, each with an atrium and ventricle . The atrium and ventricles of each side are separated by atrioventricular valves which prevent back flow from one chamber to the next during contraction. Being myogenic, the heart's pace is maintained by pacemaker cells found in the sinoatrial node, located on the right atrium. The sinoatrial node uses calcium to cause a depolarising signal transduction pathway from the atrium through right and left atrioventricular bundle which communicates contraction to the ventricles. The avian heart also consists of muscular arches that are made up of thick bundles of muscular layers. Much like a mammalian heart, the avian heart is composed of endocardial , myocardial and epicardial layers. The atrium walls tend to be thinner than the ventricle walls, due to the intense ventricular contraction used to pump oxygenated blood throughout the body. Avian hearts are generally larger than mammalian hearts when compared to body mass. This adaptation allows more blood to be pumped to meet the high metabolic need associated with flight. Birds have a very efficient system for diffusing oxygen into the blood; birds have a ten times greater surface area to gas exchange volume than mammals. As a result, birds have more blood in their capillaries per unit of volume of lung than a mammal. The arteries are composed of thick elastic muscles to withstand the pressure of the ventricular contractions, and become more rigid as they move away from the heart. Blood moves through the arteries, which undergo vasoconstriction , and into arterioles which act as a transportation system to distribute primarily oxygen as well as nutrients to all tissues of the body. As the arterioles move away from the heart and into individual organs and tissues they are further divided to increase surface area and slow blood flow. Blood travels through the arterioles and moves into the capillaries where gas exchange can occur. [ citation needed ] Capillaries are organised into capillary beds in tissues; it is here that blood exchanges oxygen for carbon dioxide waste. In the capillary beds, blood flow is slowed to allow maximum diffusion of oxygen into the tissues. Once the blood has become deoxygenated, it travels through venules then veins and back to the heart. Veins, unlike arteries, are thin and rigid as they do not need to withstand extreme pressure. As blood travels through the venules to the veins a funneling occurs called vasodilation bringing blood back to the heart. Once the blood reaches the heart, it moves first into the right atrium, then the right ventricle to be pumped through the lungs for further gas exchange of carbon dioxide waste for oxygen. Oxygenated blood then flows from the lungs through the left atrium to the left ventricle where it is pumped out to the body. [ citation needed ]The nervous system is large relative to the bird's size. The most developed part of the brain of birds is the one that controls the flight-related functions, while the cerebellum coordinates movement and the cerebrum controls behaviour patterns, navigation, mating and nest building. Most birds have a poor sense of smell with notable exceptions including kiwis , New World vultures and tubenoses . The avian visual system is usually highly developed. Water birds have special flexible lenses, allowing accommodation for vision in air and water. Some species also have dual fovea . Birds are tetrachromatic , possessing ultraviolet (UV) sensitive cone cells in the eye as well as green, red and blue ones. They also have double cones , likely to mediate achromatic vision . Many birds show plumage patterns in ultraviolet that are invisible to the human eye; some birds whose sexes appear similar to the naked eye are distinguished by the presence of ultraviolet reflective patches on their feathers. Male blue tits have an ultraviolet reflective crown patch which is displayed in courtship by posturing and raising of their nape feathers. Ultraviolet light is also used in foraging— kestrels have been shown to search for prey by detecting the UV reflective urine trail marks left on the ground by rodents. With the exception of pigeons and a few other species, the eyelids of birds are not used in blinking. Instead the eye is lubricated by the nictitating membrane , a third eyelid that moves horizontally. The nictitating membrane also covers the eye and acts as a contact lens in many aquatic birds. The bird retina has a fan shaped blood supply system called the pecten . Eyes of most birds are large, not very round and capable of only limited movement in the orbits, typically 10–20°. Birds with eyes on the sides of their heads have a wide visual field , while birds with eyes on the front of their heads, such as owls, have binocular vision and can estimate the depth of field . The avian ear lacks external pinnae but is covered by feathers, although in some birds, such as the Asio , Bubo and Otus owls , these feathers form tufts which resemble ears. The inner ear has a cochlea , but it is not spiral as in mammals. A few species are able to use chemical defences against predators; some Procellariiformes can eject an unpleasant stomach oil against an aggressor, and some species of pitohuis from New Guinea have a powerful neurotoxin in their skin and feathers. A lack of field observations limit our knowledge, but intraspecific conflicts are known to sometimes result in injury or death. The screamers ( Anhimidae ), some jacanas ( Jacana , Hydrophasianus ), the spur-winged goose ( Plectropterus ), the torrent duck ( Merganetta ) and nine species of lapwing ( Vanellus ) use a sharp spur on the wing as a weapon. The steamer ducks ( Tachyeres ), geese and swans ( Anserinae ), the solitaire ( Pezophaps ), sheathbills ( Chionis ), some guans ( Crax ) and stone curlews ( Burhinus ) use a bony knob on the alular metacarpal to punch and hammer opponents. The jacanas Actophilornis and Irediparra have an expanded, blade-like radius. The extinct Xenicibis was unique in having an elongate forelimb and massive hand which likely functioned in combat or defence as a jointed club or flail. Swans , for instance, may strike with the bony spurs and bite when defending eggs or young. Feathers are a feature characteristic of birds (though also present in some dinosaurs not currently considered to be true birds). They facilitate flight , provide insulation that aids in thermoregulation , and are used in display, camouflage, and signalling. There are several types of feathers, each serving its own set of purposes. Feathers are epidermal growths attached to the skin and arise only in specific tracts of skin called pterylae . The distribution pattern of these feather tracts (pterylosis) is used in taxonomy and systematics. The arrangement and appearance of feathers on the body, called plumage , may vary within species by age, social status , and sex . Plumage is regularly moulted ; the standard plumage of a bird that has moulted after breeding is known as the " non-breeding " plumage, or—in the Humphrey–Parkes terminology —"basic" plumage; breeding plumages or variations of the basic plumage are known under the Humphrey–Parkes system as " alternate " plumages. Moulting is annual in most species, although some may have two moults a year, and large birds of prey may moult only once every few years. Moulting patterns vary across species. In passerines, flight feathers are replaced one at a time with the innermost primary being the first. When the fifth of sixth primary is replaced, the outermost tertiaries begin to drop. After the innermost tertiaries are moulted, the secondaries starting from the innermost begin to drop and this proceeds to the outer feathers (centrifugal moult). The greater primary coverts are moulted in synchrony with the primary that they overlap. A small number of species, such as ducks and geese, lose all of their flight feathers at once, temporarily becoming flightless. As a general rule, the tail feathers are moulted and replaced starting with the innermost pair. Centripetal moults of tail feathers are however seen in the Phasianidae . The centrifugal moult is modified in the tail feathers of woodpeckers and treecreepers , in that it begins with the second innermost pair of feathers and finishes with the central pair of feathers so that the bird maintains a functional climbing tail. The general pattern seen in passerines is that the primaries are replaced outward, secondaries inward, and the tail from centre outward. Before nesting, the females of most bird species gain a bare brood patch by losing feathers close to the belly. The skin there is well supplied with blood vessels and helps the bird in incubation. Feathers require maintenance and birds preen or groom them daily, spending an average of around 9% of their daily time on this. The bill is used to brush away foreign particles and to apply waxy secretions from the uropygial gland ; these secretions protect the feathers' flexibility and act as an antimicrobial agent , inhibiting the growth of feather-degrading bacteria . This may be supplemented with the secretions of formic acid from ants, which birds receive through a behaviour known as anting , to remove feather parasites. The scales of birds are composed of the same keratin as beaks, claws, and spurs. They are found mainly on the toes and metatarsus , but may be found further up on the ankle in some birds. Most bird scales do not overlap significantly, except in the cases of kingfishers and woodpeckers . The scales of birds are thought to be homologous to those of reptiles and mammals. Most birds can fly , which distinguishes them from almost all other vertebrate classes. Flight is the primary means of locomotion for most bird species and is used for searching for food and for escaping from predators. Birds have various adaptations for flight, including a lightweight skeleton, two large flight muscles, the pectoralis (which accounts for 15% of the total mass of the bird) and the supracoracoideus, as well as a modified forelimb ( wing ) that serves as an aerofoil . Wing shape and size generally determine a bird's flight style and performance; many birds combine powered, flapping flight with less energy-intensive soaring flight. About 60 extant bird species are flightless , as were many extinct birds. Flightlessness often arises in birds on isolated islands, most likely due to limited resources and the absence of mammalian land predators. Flightlessness is almost exclusively correlated with gigantism due to an island's inherent condition of isolation. Although flightless, penguins use similar musculature and movements to "fly" through the water, as do some flight-capable birds such as auks , shearwaters and dippers . Most birds are diurnal , but some birds, such as many species of owls and nightjars , are nocturnal or crepuscular (active during twilight hours), and many coastal waders feed when the tides are appropriate, by day or night. Birds' diets are varied and often include nectar , fruit, plants, seeds, carrion , and various small animals, including other birds. The digestive system of birds is unique, with a crop for storage and a gizzard that contains swallowed stones for grinding food to compensate for the lack of teeth. Some species such as pigeons and some psittacine species do not have a gallbladder . Most birds are highly adapted for rapid digestion to aid with flight. Some migratory birds have adapted to use protein stored in many parts of their bodies, including protein from the intestines, as additional energy during migration. Birds that employ many strategies to obtain food or feed on a variety of food items are called generalists, while others that concentrate time and effort on specific food items or have a single strategy to obtain food are considered specialists. Avian foraging strategies can vary widely by species. Many birds glean for insects, invertebrates, fruit, or seeds. Some hunt insects by suddenly attacking from a branch. Those species that seek pest insects are considered beneficial 'biological control agents' and their presence encouraged in biological pest control programmes. Combined, insectivorous birds eat 400–500 million metric tons of arthropods annually. Nectar feeders such as hummingbirds , sunbirds , lories, and lorikeets amongst others have specially adapted brushy tongues and in many cases bills designed to fit co-adapted flowers. Kiwis and shorebirds with long bills probe for invertebrates; shorebirds' varied bill lengths and feeding methods result in the separation of ecological niches . Loons , diving ducks , penguins and auks pursue their prey underwater, using their wings or feet for propulsion, while aerial predators such as sulids , kingfishers and terns plunge dive after their prey. Flamingos , three species of prion , and some ducks are filter feeders . Geese and dabbling ducks are primarily grazers. Some species, including frigatebirds , gulls , and skuas , engage in kleptoparasitism , stealing food items from other birds. Kleptoparasitism is thought to be a supplement to food obtained by hunting, rather than a significant part of any species' diet; a study of great frigatebirds stealing from masked boobies estimated that the frigatebirds stole at most 40% of their food and on average stole only 5%. Other birds are scavengers ; some of these, like vultures , are specialised carrion eaters, while others, like gulls, corvids , or other birds of prey, are opportunists. Water is needed by many birds although their mode of excretion and lack of sweat glands reduces the physiological demands. Some desert birds can obtain their water needs entirely from moisture in their food. Some have other adaptations such as allowing their body temperature to rise, saving on moisture loss from evaporative cooling or panting. Seabirds can drink seawater and have salt glands inside the head that eliminate excess salt out of the nostrils. Most birds scoop water in their beaks and raise their head to let water run down the throat. Some species, especially of arid zones, belonging to the pigeon , finch , mousebird , button-quail and bustard families are capable of sucking up water without the need to tilt back their heads. Some desert birds depend on water sources and sandgrouse are particularly well known for congregating daily at waterholes. Nesting sandgrouse and many plovers carry water to their young by wetting their belly feathers. Some birds carry water for chicks at the nest in their crop or regurgitate it along with food. The pigeon family, flamingos and penguins have adaptations to produce a nutritive fluid called crop milk that they provide to their chicks. Feathers, being critical to the survival of a bird, require maintenance. Apart from physical wear and tear, feathers face the onslaught of fungi, ectoparasitic feather mites and bird lice . The physical condition of feathers are maintained by preening often with the application of secretions from the preen gland . Birds also bathe in water or dust themselves. While some birds dip into shallow water, more aerial species may make aerial dips into water and arboreal species often make use of dew or rain that collect on leaves. Birds of arid regions make use of loose soil to dust-bathe. A behaviour termed as anting in which the bird encourages ants to run through their plumage is also thought to help them reduce the ectoparasite load in feathers. Many species will spread out their wings and expose them to direct sunlight and this too is thought to help in reducing fungal and ectoparasitic activity that may lead to feather damage. Many bird species migrate to take advantage of global differences of seasonal temperatures, therefore optimising availability of food sources and breeding habitat. These migrations vary among the different groups. Many landbirds, shorebirds , and waterbirds undertake annual long-distance migrations, usually triggered by the length of daylight as well as weather conditions. These birds are characterised by a breeding season spent in the temperate or polar regions and a non-breeding season in the tropical regions or opposite hemisphere. Before migration, birds substantially increase body fats and reserves and reduce the size of some of their organs. Migration is highly demanding energetically, particularly as birds need to cross deserts and oceans without refuelling. Landbirds have a flight range of around 2,500 km (1,600 mi) and shorebirds can fly up to 4,000 km (2,500 mi) , although the bar-tailed godwit is capable of non-stop flights of up to 10,200 km (6,300 mi) . Some Seabirds undertake long migrations, with the longest annual migrations including those of Arctic terns , which were recorded travelling an average of 70,900 km (44,100 mi) between their Arctic breeding grounds in Greenland and Iceland and their wintering grounds in Antarctica , with one bird covering 81,600 km (50,700 mi) , and sooty shearwaters , which nest in New Zealand and Chile and make annual round trips of 64,000 km (39,800 mi) to their summer feeding grounds in the North Pacific off Japan, Alaska and California . Other seabirds disperse after breeding, travelling widely but having no set migration route. Albatrosses nesting in the Southern Ocean often undertake circumpolar trips between breeding seasons. Some bird species undertake shorter migrations, travelling only as far as is required to avoid bad weather or obtain food. Irruptive species such as the boreal finches are one such group and can commonly be found at a location in one year and absent the next. This type of migration is normally associated with food availability. Species may also travel shorter distances over part of their range, with individuals from higher latitudes travelling into the existing range of conspecifics; others undertake partial migrations, where only a fraction of the population, usually females and subdominant males, migrates. Partial migration can form a large percentage of the migration behaviour of birds in some regions; in Australia, surveys found that 44% of non-passerine birds and 32% of passerines were partially migratory. Altitudinal migration is a form of short-distance migration in which birds spend the breeding season at higher altitudes and move to lower ones during suboptimal conditions. It is most often triggered by temperature changes and usually occurs when the normal territories also become inhospitable due to lack of food. Some species may also be nomadic, holding no fixed territory and moving according to weather and food availability. Parrots as a family are overwhelmingly neither migratory nor sedentary but considered to either be dispersive, irruptive, nomadic or undertake small and irregular migrations. The ability of birds to return to precise locations across vast distances has been known for some time; in an experiment conducted in the 1950s, a Manx shearwater released in Boston in the United States returned to its colony in Skomer , in Wales within 13 days, a distance of 5,150 km (3,200 mi) . Birds navigate during migration using a variety of methods. For diurnal migrants, the sun is used to navigate by day, and a stellar compass is used at night. Birds that use the sun compensate for the changing position of the sun during the day by the use of an internal clock . Orientation with the stellar compass depends on the position of the constellations surrounding Polaris . These are backed up in some species by their ability to sense the Earth's geomagnetism through specialised photoreceptors . Birds communicate primarily using visual and auditory signals. Signals can be interspecific (between species) and intraspecific (within species). Birds sometimes use plumage to assess and assert social dominance, to display breeding condition in sexually selected species, or to make threatening displays, as in the sunbittern 's mimicry of a large predator to ward off hawks and protect young chicks. Visual communication among birds may also involve ritualised displays, which have developed from non-signalling actions such as preening, the adjustments of feather position, pecking, or other behaviour. These displays may signal aggression or submission or may contribute to the formation of pair-bonds. The most elaborate displays occur during courtship, where "dances" are often formed from complex combinations of many possible component movements; males' breeding success may depend on the quality of such displays. Bird calls and songs , which are produced in the syrinx , are the major means by which birds communicate with sound . This communication can be very complex; some species can operate the two sides of the syrinx independently, allowing the simultaneous production of two different songs. Calls are used for a variety of purposes, including mate attraction, evaluation of potential mates, bond formation, the claiming and maintenance of territories, the identification of other individuals (such as when parents look for chicks in colonies or when mates reunite at the start of breeding season), and the warning of other birds of potential predators, sometimes with specific information about the nature of the threat. Some birds also use mechanical sounds for auditory communication. The Coenocorypha snipes of New Zealand drive air through their feathers, woodpeckers drum for long-distance communication, and palm cockatoos use tools to drum. While some birds are essentially territorial or live in small family groups, other birds may form large flocks . The principal benefits of flocking are safety in numbers and increased foraging efficiency. Defence against predators is particularly important in closed habitats like forests, where ambush predation is common and multiple eyes can provide a valuable early warning system . This has led to the development of many mixed-species feeding flocks , which are usually composed of small numbers of many species; these flocks provide safety in numbers but increase potential competition for resources. Costs of flocking include bullying of socially subordinate birds by more dominant birds and the reduction of feeding efficiency in certain cases. Some species have a mixed system with breeding pairs maintaining territories, while unmated or young birds live in flocks where they secure mates prior to finding territories. Birds sometimes also form associations with non-avian species. Plunge-diving seabirds associate with dolphins and tuna , which push shoaling fish towards the surface. Some species of hornbills have a mutualistic relationship with dwarf mongooses , in which they forage together and warn each other of nearby birds of prey and other predators. The high metabolic rates of birds during the active part of the day is supplemented by rest at other times. Sleeping birds often use a type of sleep known as vigilant sleep, where periods of rest are interspersed with quick eye-opening "peeks", allowing them to be sensitive to disturbances and enable rapid escape from threats. Swifts are believed to be able to sleep in flight and radar observations suggest that they orient themselves to face the wind in their roosting flight. It has been suggested that there may be certain kinds of sleep which are possible even when in flight. Some birds have also demonstrated the capacity to fall into slow-wave sleep one hemisphere of the brain at a time. The birds tend to exercise this ability depending upon its position relative to the outside of the flock. This may allow the eye opposite the sleeping hemisphere to remain vigilant for predators by viewing the outer margins of the flock. This adaptation is also known from marine mammals . Communal roosting is common because it lowers the loss of body heat and decreases the risks associated with predators. Roosting sites are often chosen with regard to thermoregulation and safety. Unusual mobile roost sites include large herbivores on the African savanna that are used by oxpeckers . Many sleeping birds bend their heads over their backs and tuck their bills in their back feathers, although others place their beaks among their breast feathers. Many birds rest on one leg, while some may pull up their legs into their feathers, especially in cold weather. Perching birds have a tendon-locking mechanism that helps them hold on to the perch when they are asleep. Many ground birds, such as quails and pheasants, roost in trees. A few parrots of the genus Loriculus roost hanging upside down. Some hummingbirds go into a nightly state of torpor accompanied with a reduction of their metabolic rates. This physiological adaptation shows in nearly a hundred other species, including owlet-nightjars , nightjars , and woodswallows . One species, the common poorwill , even enters a state of hibernation . Birds do not have sweat glands, but can lose water directly through the skin, and they may cool themselves by moving to shade, standing in water, panting, increasing their surface area, fluttering their throat or using special behaviours like urohidrosis to cool themselves. Ninety-five per cent of bird species are socially monogamous. These species pair for at least the length of the breeding season or—in some cases—for several years or until the death of one mate. Monogamy allows for both paternal care and biparental care , which is especially important for species in which care from both the female and the male parent is required in order to successfully rear a brood. Among many socially monogamous species, extra-pair copulation (infidelity) is common. Such behaviour typically occurs between dominant males and females paired with subordinate males, but may also be the result of forced copulation in ducks and other anatids . For females, possible benefits of extra-pair copulation include getting better genes for her offspring and insuring against the possibility of infertility in her mate. Males of species that engage in extra-pair copulations will closely guard their mates to ensure the parentage of the offspring that they raise. Other mating systems, including polygyny , polyandry , polygamy , polygynandry , and promiscuity , also occur. Polygamous breeding systems arise when females are able to raise broods without the help of males. Mating systems vary across bird families but variations within species are thought to be driven by environmental conditions. A unique system is the formation of trios where a third individual is allowed by a breeding pair temporarily into the territory to assist with brood raising thereby leading to higher fitness. Breeding usually involves some form of courtship display, typically performed by the male. Most displays are rather simple and involve some type of song . Some displays, however, are quite elaborate. Depending on the species, these may include wing or tail drumming, dancing, aerial flights, or communal lekking . Females are generally the ones that drive partner selection, although in the polyandrous phalaropes , this is reversed: plainer males choose brightly coloured females. Courtship feeding , billing and allopreening are commonly performed between partners, generally after the birds have paired and mated. Homosexual behaviour has been observed in males or females in numerous species of birds, including copulation, pair-bonding, and joint parenting of chicks. Over 130 avian species around the world engage in sexual interactions between the same sex or homosexual behaviours. "Same-sex courtship activities may involve elaborate displays, synchronised dances, gift-giving ceremonies, or behaviours at specific display areas including bowers, arenas, or leks." Many birds actively defend a territory from others of the same species during the breeding season; maintenance of territories protects the food source for their chicks. Species that are unable to defend feeding territories, such as seabirds and swifts , often breed in colonies instead; this is thought to offer protection from predators. Colonial breeders defend small nesting sites, and competition between and within species for nesting sites can be intense. All birds lay amniotic eggs with hard shells made mostly of calcium carbonate . Hole and burrow nesting species tend to lay white or pale eggs, while open nesters lay camouflaged eggs. There are many exceptions to this pattern, however; the ground-nesting nightjars have pale eggs, and camouflage is instead provided by their plumage. Species that are victims of brood parasites have varying egg colours to improve the chances of spotting a parasite's egg, which forces female parasites to match their eggs to those of their hosts. Bird eggs are usually laid in a nest . Most species create somewhat elaborate nests, which can be cups, domes, plates, mounds, or burrows. Some bird nests can be a simple scrape, with minimal or no lining; most seabird and wader nests are no more than a scrape on the ground. Most birds build nests in sheltered, hidden areas to avoid predation, but large or colonial birds—which are more capable of defence—may build more open nests. During nest construction, some species seek out plant matter from plants with parasite-reducing toxins to improve chick survival, and feathers are often used for nest insulation. Some bird species have no nests; the cliff-nesting common guillemot lays its eggs on bare rock, and male emperor penguins keep eggs between their body and feet. The absence of nests is especially prevalent in open habitat ground-nesting species where any addition of nest material would make the nest more conspicuous. Many ground nesting birds lay a clutch of eggs that hatch synchronously, with precocial chicks led away from the nests ( nidifugous ) by their parents soon after hatching. Incubation , which regulates temperature for chick development, usually begins after the last egg has been laid. In monogamous species incubation duties are often shared, whereas in polygamous species one parent is wholly responsible for incubation. Warmth from parents passes to the eggs through brood patches , areas of bare skin on the abdomen or breast of the incubating birds. Incubation can be an energetically demanding process; adult albatrosses, for instance, lose as much as 83 grams (2.9 oz) of body weight per day of incubation. The warmth for the incubation of the eggs of megapodes comes from the sun, decaying vegetation or volcanic sources. Incubation periods range from 10 days (in woodpeckers , cuckoos and passerine birds) to over 80 days (in albatrosses and kiwis ). The diversity of characteristics of birds is great, sometimes even in closely related species. Several avian characteristics are compared in the table below. At the time of their hatching, chicks range in development from helpless to independent, depending on their species. Helpless chicks are termed altricial , and tend to be born small, blind , immobile and naked; chicks that are mobile and feathered upon hatching are termed precocial . Altricial chicks need help thermoregulating and must be brooded for longer than precocial chicks. The young of many bird species do not precisely fit into either the precocial or altricial category, having some aspects of each and thus fall somewhere on an "altricial-precocial spectrum". Chicks at neither extreme but favouring one or the other may be termed semi-precocial or semi-altricial . The length and nature of parental care varies widely amongst different orders and species. At one extreme, parental care in megapodes ends at hatching; the newly hatched chick digs itself out of the nest mound without parental assistance and can fend for itself immediately. At the other extreme, many seabirds have extended periods of parental care, the longest being that of the great frigatebird , whose chicks take up to six months to fledge and are fed by the parents for up to an additional 14 months. The chick guard stage describes the period of breeding during which one of the adult birds is permanently present at the nest after chicks have hatched. The main purpose of the guard stage is to aid offspring to thermoregulate and protect them from predation. In some species, both parents care for nestlings and fledglings; in others, such care is the responsibility of only one sex. In some species, other members of the same species—usually close relatives of the breeding pair , such as offspring from previous broods—will help with the raising of the young. Such alloparenting is particularly common among the Corvida , which includes such birds as the true crows , Australian magpie and fairy-wrens , but has been observed in species as different as the rifleman and red kite . Among most groups of animals, male parental care is rare. In birds, however, it is quite common—more so than in any other vertebrate class. Although territory and nest site defence, incubation, and chick feeding are often shared tasks, there is sometimes a division of labour in which one mate undertakes all or most of a particular duty. The point at which chicks fledge varies dramatically. The chicks of the Synthliboramphus murrelets, like the ancient murrelet , leave the nest the night after they hatch, following their parents out to sea, where they are raised away from terrestrial predators. Some other species, such as ducks, move their chicks away from the nest at an early age. In most species, chicks leave the nest just before, or soon after, they are able to fly. The amount of parental care after fledging varies; albatross chicks leave the nest on their own and receive no further help, while other species continue some supplementary feeding after fledging. Chicks may also follow their parents during their first migration . Brood parasitism , in which an egg-layer leaves her eggs with another individual's brood, is more common among birds than any other type of organism. After a parasitic bird lays her eggs in another bird's nest, they are often accepted and raised by the host at the expense of the host's own brood. Brood parasites may be either obligate brood parasites , which must lay their eggs in the nests of other species because they are incapable of raising their own young, or non-obligate brood parasites , which sometimes lay eggs in the nests of conspecifics to increase their reproductive output even though they could have raised their own young. One hundred bird species, including honeyguides , icterids , and ducks , are obligate parasites, though the most famous are the cuckoos . Some brood parasites are adapted to hatch before their host's young, which allows them to destroy the host's eggs by pushing them out of the nest or to kill the host's chicks; this ensures that all food brought to the nest will be fed to the parasitic chicks. Birds have evolved a variety of mating behaviours, with the peacock tail being perhaps the most famous example of sexual selection and the Fisherian runaway . Commonly occurring sexual dimorphisms such as size and colour differences are energetically costly attributes that signal competitive breeding situations. Many types of avian sexual selection have been identified; intersexual selection, also known as female choice; and intrasexual competition, where individuals of the more abundant sex compete with each other for the privilege to mate. Sexually selected traits often evolve to become more pronounced in competitive breeding situations until the trait begins to limit the individual's fitness. Conflicts between an individual fitness and signalling adaptations ensure that sexually selected ornaments such as plumage colouration and courtship behaviour are "honest" traits. Signals must be costly to ensure that only good-quality individuals can present these exaggerated sexual ornaments and behaviours. Inbreeding causes early death ( inbreeding depression ) in the zebra finch Taeniopygia guttata . Embryo survival (that is, hatching success of fertile eggs) was significantly lower for sib-sib mating pairs than for unrelated pairs. Darwin's finch Geospiza scandens experiences inbreeding depression (reduced survival of offspring) and the magnitude of this effect is influenced by environmental conditions such as low food availability. Incestuous matings by the purple-crowned fairy wren Malurus coronatus result in severe fitness costs due to inbreeding depression (greater than 30% reduction in hatchability of eggs). Females paired with related males may undertake extra pair matings (see Promiscuity#Other animals for 90% frequency in avian species) that can reduce the negative effects of inbreeding. However, there are ecological and demographic constraints on extra pair matings. Nevertheless, 43% of broods produced by incestuously paired females contained extra pair young. Inbreeding depression occurs in the great tit ( Parus major ) when the offspring produced as a result of a mating between close relatives show reduced fitness. In natural populations of Parus major , inbreeding is avoided by dispersal of individuals from their birthplace, which reduces the chance of mating with a close relative. Southern pied babblers Turdoides bicolor appear to avoid inbreeding in two ways. The first is through dispersal, and the second is by avoiding familiar group members as mates. Cooperative breeding in birds typically occurs when offspring, usually males, delay dispersal from their natal group in order to remain with the family to help rear younger kin. Female offspring rarely stay at home, dispersing over distances that allow them to breed independently, or to join unrelated groups. In general, inbreeding is avoided because it leads to a reduction in progeny fitness ( inbreeding depression ) due largely to the homozygous expression of deleterious recessive alleles. Cross-fertilisation between unrelated individuals ordinarily leads to the masking of deleterious recessive alleles in progeny. Birds' diets are varied and often include nectar , fruit, plants, seeds, carrion , and various small animals, including other birds. The digestive system of birds is unique, with a crop for storage and a gizzard that contains swallowed stones for grinding food to compensate for the lack of teeth. Some species such as pigeons and some psittacine species do not have a gallbladder . Most birds are highly adapted for rapid digestion to aid with flight. Some migratory birds have adapted to use protein stored in many parts of their bodies, including protein from the intestines, as additional energy during migration. Birds that employ many strategies to obtain food or feed on a variety of food items are called generalists, while others that concentrate time and effort on specific food items or have a single strategy to obtain food are considered specialists. Avian foraging strategies can vary widely by species. Many birds glean for insects, invertebrates, fruit, or seeds. Some hunt insects by suddenly attacking from a branch. Those species that seek pest insects are considered beneficial 'biological control agents' and their presence encouraged in biological pest control programmes. Combined, insectivorous birds eat 400–500 million metric tons of arthropods annually. Nectar feeders such as hummingbirds , sunbirds , lories, and lorikeets amongst others have specially adapted brushy tongues and in many cases bills designed to fit co-adapted flowers. Kiwis and shorebirds with long bills probe for invertebrates; shorebirds' varied bill lengths and feeding methods result in the separation of ecological niches . Loons , diving ducks , penguins and auks pursue their prey underwater, using their wings or feet for propulsion, while aerial predators such as sulids , kingfishers and terns plunge dive after their prey. Flamingos , three species of prion , and some ducks are filter feeders . Geese and dabbling ducks are primarily grazers. Some species, including frigatebirds , gulls , and skuas , engage in kleptoparasitism , stealing food items from other birds. Kleptoparasitism is thought to be a supplement to food obtained by hunting, rather than a significant part of any species' diet; a study of great frigatebirds stealing from masked boobies estimated that the frigatebirds stole at most 40% of their food and on average stole only 5%. Other birds are scavengers ; some of these, like vultures , are specialised carrion eaters, while others, like gulls, corvids , or other birds of prey, are opportunists. Water is needed by many birds although their mode of excretion and lack of sweat glands reduces the physiological demands. Some desert birds can obtain their water needs entirely from moisture in their food. Some have other adaptations such as allowing their body temperature to rise, saving on moisture loss from evaporative cooling or panting. Seabirds can drink seawater and have salt glands inside the head that eliminate excess salt out of the nostrils. Most birds scoop water in their beaks and raise their head to let water run down the throat. Some species, especially of arid zones, belonging to the pigeon , finch , mousebird , button-quail and bustard families are capable of sucking up water without the need to tilt back their heads. Some desert birds depend on water sources and sandgrouse are particularly well known for congregating daily at waterholes. Nesting sandgrouse and many plovers carry water to their young by wetting their belly feathers. Some birds carry water for chicks at the nest in their crop or regurgitate it along with food. The pigeon family, flamingos and penguins have adaptations to produce a nutritive fluid called crop milk that they provide to their chicks. Feathers, being critical to the survival of a bird, require maintenance. Apart from physical wear and tear, feathers face the onslaught of fungi, ectoparasitic feather mites and bird lice . The physical condition of feathers are maintained by preening often with the application of secretions from the preen gland . Birds also bathe in water or dust themselves. While some birds dip into shallow water, more aerial species may make aerial dips into water and arboreal species often make use of dew or rain that collect on leaves. Birds of arid regions make use of loose soil to dust-bathe. A behaviour termed as anting in which the bird encourages ants to run through their plumage is also thought to help them reduce the ectoparasite load in feathers. Many species will spread out their wings and expose them to direct sunlight and this too is thought to help in reducing fungal and ectoparasitic activity that may lead to feather damage. Many bird species migrate to take advantage of global differences of seasonal temperatures, therefore optimising availability of food sources and breeding habitat. These migrations vary among the different groups. Many landbirds, shorebirds , and waterbirds undertake annual long-distance migrations, usually triggered by the length of daylight as well as weather conditions. These birds are characterised by a breeding season spent in the temperate or polar regions and a non-breeding season in the tropical regions or opposite hemisphere. Before migration, birds substantially increase body fats and reserves and reduce the size of some of their organs. Migration is highly demanding energetically, particularly as birds need to cross deserts and oceans without refuelling. Landbirds have a flight range of around 2,500 km (1,600 mi) and shorebirds can fly up to 4,000 km (2,500 mi) , although the bar-tailed godwit is capable of non-stop flights of up to 10,200 km (6,300 mi) . Some Seabirds undertake long migrations, with the longest annual migrations including those of Arctic terns , which were recorded travelling an average of 70,900 km (44,100 mi) between their Arctic breeding grounds in Greenland and Iceland and their wintering grounds in Antarctica , with one bird covering 81,600 km (50,700 mi) , and sooty shearwaters , which nest in New Zealand and Chile and make annual round trips of 64,000 km (39,800 mi) to their summer feeding grounds in the North Pacific off Japan, Alaska and California . Other seabirds disperse after breeding, travelling widely but having no set migration route. Albatrosses nesting in the Southern Ocean often undertake circumpolar trips between breeding seasons. Some bird species undertake shorter migrations, travelling only as far as is required to avoid bad weather or obtain food. Irruptive species such as the boreal finches are one such group and can commonly be found at a location in one year and absent the next. This type of migration is normally associated with food availability. Species may also travel shorter distances over part of their range, with individuals from higher latitudes travelling into the existing range of conspecifics; others undertake partial migrations, where only a fraction of the population, usually females and subdominant males, migrates. Partial migration can form a large percentage of the migration behaviour of birds in some regions; in Australia, surveys found that 44% of non-passerine birds and 32% of passerines were partially migratory. Altitudinal migration is a form of short-distance migration in which birds spend the breeding season at higher altitudes and move to lower ones during suboptimal conditions. It is most often triggered by temperature changes and usually occurs when the normal territories also become inhospitable due to lack of food. Some species may also be nomadic, holding no fixed territory and moving according to weather and food availability. Parrots as a family are overwhelmingly neither migratory nor sedentary but considered to either be dispersive, irruptive, nomadic or undertake small and irregular migrations. The ability of birds to return to precise locations across vast distances has been known for some time; in an experiment conducted in the 1950s, a Manx shearwater released in Boston in the United States returned to its colony in Skomer , in Wales within 13 days, a distance of 5,150 km (3,200 mi) . Birds navigate during migration using a variety of methods. For diurnal migrants, the sun is used to navigate by day, and a stellar compass is used at night. Birds that use the sun compensate for the changing position of the sun during the day by the use of an internal clock . Orientation with the stellar compass depends on the position of the constellations surrounding Polaris . These are backed up in some species by their ability to sense the Earth's geomagnetism through specialised photoreceptors . Birds communicate primarily using visual and auditory signals. Signals can be interspecific (between species) and intraspecific (within species). Birds sometimes use plumage to assess and assert social dominance, to display breeding condition in sexually selected species, or to make threatening displays, as in the sunbittern 's mimicry of a large predator to ward off hawks and protect young chicks. Visual communication among birds may also involve ritualised displays, which have developed from non-signalling actions such as preening, the adjustments of feather position, pecking, or other behaviour. These displays may signal aggression or submission or may contribute to the formation of pair-bonds. The most elaborate displays occur during courtship, where "dances" are often formed from complex combinations of many possible component movements; males' breeding success may depend on the quality of such displays. Bird calls and songs , which are produced in the syrinx , are the major means by which birds communicate with sound . This communication can be very complex; some species can operate the two sides of the syrinx independently, allowing the simultaneous production of two different songs. Calls are used for a variety of purposes, including mate attraction, evaluation of potential mates, bond formation, the claiming and maintenance of territories, the identification of other individuals (such as when parents look for chicks in colonies or when mates reunite at the start of breeding season), and the warning of other birds of potential predators, sometimes with specific information about the nature of the threat. Some birds also use mechanical sounds for auditory communication. The Coenocorypha snipes of New Zealand drive air through their feathers, woodpeckers drum for long-distance communication, and palm cockatoos use tools to drum. While some birds are essentially territorial or live in small family groups, other birds may form large flocks . The principal benefits of flocking are safety in numbers and increased foraging efficiency. Defence against predators is particularly important in closed habitats like forests, where ambush predation is common and multiple eyes can provide a valuable early warning system . This has led to the development of many mixed-species feeding flocks , which are usually composed of small numbers of many species; these flocks provide safety in numbers but increase potential competition for resources. Costs of flocking include bullying of socially subordinate birds by more dominant birds and the reduction of feeding efficiency in certain cases. Some species have a mixed system with breeding pairs maintaining territories, while unmated or young birds live in flocks where they secure mates prior to finding territories. Birds sometimes also form associations with non-avian species. Plunge-diving seabirds associate with dolphins and tuna , which push shoaling fish towards the surface. Some species of hornbills have a mutualistic relationship with dwarf mongooses , in which they forage together and warn each other of nearby birds of prey and other predators. The high metabolic rates of birds during the active part of the day is supplemented by rest at other times. Sleeping birds often use a type of sleep known as vigilant sleep, where periods of rest are interspersed with quick eye-opening "peeks", allowing them to be sensitive to disturbances and enable rapid escape from threats. Swifts are believed to be able to sleep in flight and radar observations suggest that they orient themselves to face the wind in their roosting flight. It has been suggested that there may be certain kinds of sleep which are possible even when in flight. Some birds have also demonstrated the capacity to fall into slow-wave sleep one hemisphere of the brain at a time. The birds tend to exercise this ability depending upon its position relative to the outside of the flock. This may allow the eye opposite the sleeping hemisphere to remain vigilant for predators by viewing the outer margins of the flock. This adaptation is also known from marine mammals . Communal roosting is common because it lowers the loss of body heat and decreases the risks associated with predators. Roosting sites are often chosen with regard to thermoregulation and safety. Unusual mobile roost sites include large herbivores on the African savanna that are used by oxpeckers . Many sleeping birds bend their heads over their backs and tuck their bills in their back feathers, although others place their beaks among their breast feathers. Many birds rest on one leg, while some may pull up their legs into their feathers, especially in cold weather. Perching birds have a tendon-locking mechanism that helps them hold on to the perch when they are asleep. Many ground birds, such as quails and pheasants, roost in trees. A few parrots of the genus Loriculus roost hanging upside down. Some hummingbirds go into a nightly state of torpor accompanied with a reduction of their metabolic rates. This physiological adaptation shows in nearly a hundred other species, including owlet-nightjars , nightjars , and woodswallows . One species, the common poorwill , even enters a state of hibernation . Birds do not have sweat glands, but can lose water directly through the skin, and they may cool themselves by moving to shade, standing in water, panting, increasing their surface area, fluttering their throat or using special behaviours like urohidrosis to cool themselves. Ninety-five per cent of bird species are socially monogamous. These species pair for at least the length of the breeding season or—in some cases—for several years or until the death of one mate. Monogamy allows for both paternal care and biparental care , which is especially important for species in which care from both the female and the male parent is required in order to successfully rear a brood. Among many socially monogamous species, extra-pair copulation (infidelity) is common. Such behaviour typically occurs between dominant males and females paired with subordinate males, but may also be the result of forced copulation in ducks and other anatids . For females, possible benefits of extra-pair copulation include getting better genes for her offspring and insuring against the possibility of infertility in her mate. Males of species that engage in extra-pair copulations will closely guard their mates to ensure the parentage of the offspring that they raise. Other mating systems, including polygyny , polyandry , polygamy , polygynandry , and promiscuity , also occur. Polygamous breeding systems arise when females are able to raise broods without the help of males. Mating systems vary across bird families but variations within species are thought to be driven by environmental conditions. A unique system is the formation of trios where a third individual is allowed by a breeding pair temporarily into the territory to assist with brood raising thereby leading to higher fitness. Breeding usually involves some form of courtship display, typically performed by the male. Most displays are rather simple and involve some type of song . Some displays, however, are quite elaborate. Depending on the species, these may include wing or tail drumming, dancing, aerial flights, or communal lekking . Females are generally the ones that drive partner selection, although in the polyandrous phalaropes , this is reversed: plainer males choose brightly coloured females. Courtship feeding , billing and allopreening are commonly performed between partners, generally after the birds have paired and mated. Homosexual behaviour has been observed in males or females in numerous species of birds, including copulation, pair-bonding, and joint parenting of chicks. Over 130 avian species around the world engage in sexual interactions between the same sex or homosexual behaviours. "Same-sex courtship activities may involve elaborate displays, synchronised dances, gift-giving ceremonies, or behaviours at specific display areas including bowers, arenas, or leks." Many birds actively defend a territory from others of the same species during the breeding season; maintenance of territories protects the food source for their chicks. Species that are unable to defend feeding territories, such as seabirds and swifts , often breed in colonies instead; this is thought to offer protection from predators. Colonial breeders defend small nesting sites, and competition between and within species for nesting sites can be intense. All birds lay amniotic eggs with hard shells made mostly of calcium carbonate . Hole and burrow nesting species tend to lay white or pale eggs, while open nesters lay camouflaged eggs. There are many exceptions to this pattern, however; the ground-nesting nightjars have pale eggs, and camouflage is instead provided by their plumage. Species that are victims of brood parasites have varying egg colours to improve the chances of spotting a parasite's egg, which forces female parasites to match their eggs to those of their hosts. Bird eggs are usually laid in a nest . Most species create somewhat elaborate nests, which can be cups, domes, plates, mounds, or burrows. Some bird nests can be a simple scrape, with minimal or no lining; most seabird and wader nests are no more than a scrape on the ground. Most birds build nests in sheltered, hidden areas to avoid predation, but large or colonial birds—which are more capable of defence—may build more open nests. During nest construction, some species seek out plant matter from plants with parasite-reducing toxins to improve chick survival, and feathers are often used for nest insulation. Some bird species have no nests; the cliff-nesting common guillemot lays its eggs on bare rock, and male emperor penguins keep eggs between their body and feet. The absence of nests is especially prevalent in open habitat ground-nesting species where any addition of nest material would make the nest more conspicuous. Many ground nesting birds lay a clutch of eggs that hatch synchronously, with precocial chicks led away from the nests ( nidifugous ) by their parents soon after hatching. Incubation , which regulates temperature for chick development, usually begins after the last egg has been laid. In monogamous species incubation duties are often shared, whereas in polygamous species one parent is wholly responsible for incubation. Warmth from parents passes to the eggs through brood patches , areas of bare skin on the abdomen or breast of the incubating birds. Incubation can be an energetically demanding process; adult albatrosses, for instance, lose as much as 83 grams (2.9 oz) of body weight per day of incubation. The warmth for the incubation of the eggs of megapodes comes from the sun, decaying vegetation or volcanic sources. Incubation periods range from 10 days (in woodpeckers , cuckoos and passerine birds) to over 80 days (in albatrosses and kiwis ). The diversity of characteristics of birds is great, sometimes even in closely related species. Several avian characteristics are compared in the table below. At the time of their hatching, chicks range in development from helpless to independent, depending on their species. Helpless chicks are termed altricial , and tend to be born small, blind , immobile and naked; chicks that are mobile and feathered upon hatching are termed precocial . Altricial chicks need help thermoregulating and must be brooded for longer than precocial chicks. The young of many bird species do not precisely fit into either the precocial or altricial category, having some aspects of each and thus fall somewhere on an "altricial-precocial spectrum". Chicks at neither extreme but favouring one or the other may be termed semi-precocial or semi-altricial . The length and nature of parental care varies widely amongst different orders and species. At one extreme, parental care in megapodes ends at hatching; the newly hatched chick digs itself out of the nest mound without parental assistance and can fend for itself immediately. At the other extreme, many seabirds have extended periods of parental care, the longest being that of the great frigatebird , whose chicks take up to six months to fledge and are fed by the parents for up to an additional 14 months. The chick guard stage describes the period of breeding during which one of the adult birds is permanently present at the nest after chicks have hatched. The main purpose of the guard stage is to aid offspring to thermoregulate and protect them from predation. In some species, both parents care for nestlings and fledglings; in others, such care is the responsibility of only one sex. In some species, other members of the same species—usually close relatives of the breeding pair , such as offspring from previous broods—will help with the raising of the young. Such alloparenting is particularly common among the Corvida , which includes such birds as the true crows , Australian magpie and fairy-wrens , but has been observed in species as different as the rifleman and red kite . Among most groups of animals, male parental care is rare. In birds, however, it is quite common—more so than in any other vertebrate class. Although territory and nest site defence, incubation, and chick feeding are often shared tasks, there is sometimes a division of labour in which one mate undertakes all or most of a particular duty. The point at which chicks fledge varies dramatically. The chicks of the Synthliboramphus murrelets, like the ancient murrelet , leave the nest the night after they hatch, following their parents out to sea, where they are raised away from terrestrial predators. Some other species, such as ducks, move their chicks away from the nest at an early age. In most species, chicks leave the nest just before, or soon after, they are able to fly. The amount of parental care after fledging varies; albatross chicks leave the nest on their own and receive no further help, while other species continue some supplementary feeding after fledging. Chicks may also follow their parents during their first migration . Brood parasitism , in which an egg-layer leaves her eggs with another individual's brood, is more common among birds than any other type of organism. After a parasitic bird lays her eggs in another bird's nest, they are often accepted and raised by the host at the expense of the host's own brood. Brood parasites may be either obligate brood parasites , which must lay their eggs in the nests of other species because they are incapable of raising their own young, or non-obligate brood parasites , which sometimes lay eggs in the nests of conspecifics to increase their reproductive output even though they could have raised their own young. One hundred bird species, including honeyguides , icterids , and ducks , are obligate parasites, though the most famous are the cuckoos . Some brood parasites are adapted to hatch before their host's young, which allows them to destroy the host's eggs by pushing them out of the nest or to kill the host's chicks; this ensures that all food brought to the nest will be fed to the parasitic chicks. Birds have evolved a variety of mating behaviours, with the peacock tail being perhaps the most famous example of sexual selection and the Fisherian runaway . Commonly occurring sexual dimorphisms such as size and colour differences are energetically costly attributes that signal competitive breeding situations. Many types of avian sexual selection have been identified; intersexual selection, also known as female choice; and intrasexual competition, where individuals of the more abundant sex compete with each other for the privilege to mate. Sexually selected traits often evolve to become more pronounced in competitive breeding situations until the trait begins to limit the individual's fitness. Conflicts between an individual fitness and signalling adaptations ensure that sexually selected ornaments such as plumage colouration and courtship behaviour are "honest" traits. Signals must be costly to ensure that only good-quality individuals can present these exaggerated sexual ornaments and behaviours. Inbreeding causes early death ( inbreeding depression ) in the zebra finch Taeniopygia guttata . Embryo survival (that is, hatching success of fertile eggs) was significantly lower for sib-sib mating pairs than for unrelated pairs. Darwin's finch Geospiza scandens experiences inbreeding depression (reduced survival of offspring) and the magnitude of this effect is influenced by environmental conditions such as low food availability. Incestuous matings by the purple-crowned fairy wren Malurus coronatus result in severe fitness costs due to inbreeding depression (greater than 30% reduction in hatchability of eggs). Females paired with related males may undertake extra pair matings (see Promiscuity#Other animals for 90% frequency in avian species) that can reduce the negative effects of inbreeding. However, there are ecological and demographic constraints on extra pair matings. Nevertheless, 43% of broods produced by incestuously paired females contained extra pair young. Inbreeding depression occurs in the great tit ( Parus major ) when the offspring produced as a result of a mating between close relatives show reduced fitness. In natural populations of Parus major , inbreeding is avoided by dispersal of individuals from their birthplace, which reduces the chance of mating with a close relative. Southern pied babblers Turdoides bicolor appear to avoid inbreeding in two ways. The first is through dispersal, and the second is by avoiding familiar group members as mates. Cooperative breeding in birds typically occurs when offspring, usually males, delay dispersal from their natal group in order to remain with the family to help rear younger kin. Female offspring rarely stay at home, dispersing over distances that allow them to breed independently, or to join unrelated groups. In general, inbreeding is avoided because it leads to a reduction in progeny fitness ( inbreeding depression ) due largely to the homozygous expression of deleterious recessive alleles. Cross-fertilisation between unrelated individuals ordinarily leads to the masking of deleterious recessive alleles in progeny. Ninety-five per cent of bird species are socially monogamous. These species pair for at least the length of the breeding season or—in some cases—for several years or until the death of one mate. Monogamy allows for both paternal care and biparental care , which is especially important for species in which care from both the female and the male parent is required in order to successfully rear a brood. Among many socially monogamous species, extra-pair copulation (infidelity) is common. Such behaviour typically occurs between dominant males and females paired with subordinate males, but may also be the result of forced copulation in ducks and other anatids . For females, possible benefits of extra-pair copulation include getting better genes for her offspring and insuring against the possibility of infertility in her mate. Males of species that engage in extra-pair copulations will closely guard their mates to ensure the parentage of the offspring that they raise. Other mating systems, including polygyny , polyandry , polygamy , polygynandry , and promiscuity , also occur. Polygamous breeding systems arise when females are able to raise broods without the help of males. Mating systems vary across bird families but variations within species are thought to be driven by environmental conditions. A unique system is the formation of trios where a third individual is allowed by a breeding pair temporarily into the territory to assist with brood raising thereby leading to higher fitness. Breeding usually involves some form of courtship display, typically performed by the male. Most displays are rather simple and involve some type of song . Some displays, however, are quite elaborate. Depending on the species, these may include wing or tail drumming, dancing, aerial flights, or communal lekking . Females are generally the ones that drive partner selection, although in the polyandrous phalaropes , this is reversed: plainer males choose brightly coloured females. Courtship feeding , billing and allopreening are commonly performed between partners, generally after the birds have paired and mated. Homosexual behaviour has been observed in males or females in numerous species of birds, including copulation, pair-bonding, and joint parenting of chicks. Over 130 avian species around the world engage in sexual interactions between the same sex or homosexual behaviours. "Same-sex courtship activities may involve elaborate displays, synchronised dances, gift-giving ceremonies, or behaviours at specific display areas including bowers, arenas, or leks." Many birds actively defend a territory from others of the same species during the breeding season; maintenance of territories protects the food source for their chicks. Species that are unable to defend feeding territories, such as seabirds and swifts , often breed in colonies instead; this is thought to offer protection from predators. Colonial breeders defend small nesting sites, and competition between and within species for nesting sites can be intense. All birds lay amniotic eggs with hard shells made mostly of calcium carbonate . Hole and burrow nesting species tend to lay white or pale eggs, while open nesters lay camouflaged eggs. There are many exceptions to this pattern, however; the ground-nesting nightjars have pale eggs, and camouflage is instead provided by their plumage. Species that are victims of brood parasites have varying egg colours to improve the chances of spotting a parasite's egg, which forces female parasites to match their eggs to those of their hosts. Bird eggs are usually laid in a nest . Most species create somewhat elaborate nests, which can be cups, domes, plates, mounds, or burrows. Some bird nests can be a simple scrape, with minimal or no lining; most seabird and wader nests are no more than a scrape on the ground. Most birds build nests in sheltered, hidden areas to avoid predation, but large or colonial birds—which are more capable of defence—may build more open nests. During nest construction, some species seek out plant matter from plants with parasite-reducing toxins to improve chick survival, and feathers are often used for nest insulation. Some bird species have no nests; the cliff-nesting common guillemot lays its eggs on bare rock, and male emperor penguins keep eggs between their body and feet. The absence of nests is especially prevalent in open habitat ground-nesting species where any addition of nest material would make the nest more conspicuous. Many ground nesting birds lay a clutch of eggs that hatch synchronously, with precocial chicks led away from the nests ( nidifugous ) by their parents soon after hatching. Incubation , which regulates temperature for chick development, usually begins after the last egg has been laid. In monogamous species incubation duties are often shared, whereas in polygamous species one parent is wholly responsible for incubation. Warmth from parents passes to the eggs through brood patches , areas of bare skin on the abdomen or breast of the incubating birds. Incubation can be an energetically demanding process; adult albatrosses, for instance, lose as much as 83 grams (2.9 oz) of body weight per day of incubation. The warmth for the incubation of the eggs of megapodes comes from the sun, decaying vegetation or volcanic sources. Incubation periods range from 10 days (in woodpeckers , cuckoos and passerine birds) to over 80 days (in albatrosses and kiwis ). The diversity of characteristics of birds is great, sometimes even in closely related species. Several avian characteristics are compared in the table below. At the time of their hatching, chicks range in development from helpless to independent, depending on their species. Helpless chicks are termed altricial , and tend to be born small, blind , immobile and naked; chicks that are mobile and feathered upon hatching are termed precocial . Altricial chicks need help thermoregulating and must be brooded for longer than precocial chicks. The young of many bird species do not precisely fit into either the precocial or altricial category, having some aspects of each and thus fall somewhere on an "altricial-precocial spectrum". Chicks at neither extreme but favouring one or the other may be termed semi-precocial or semi-altricial . The length and nature of parental care varies widely amongst different orders and species. At one extreme, parental care in megapodes ends at hatching; the newly hatched chick digs itself out of the nest mound without parental assistance and can fend for itself immediately. At the other extreme, many seabirds have extended periods of parental care, the longest being that of the great frigatebird , whose chicks take up to six months to fledge and are fed by the parents for up to an additional 14 months. The chick guard stage describes the period of breeding during which one of the adult birds is permanently present at the nest after chicks have hatched. The main purpose of the guard stage is to aid offspring to thermoregulate and protect them from predation. In some species, both parents care for nestlings and fledglings; in others, such care is the responsibility of only one sex. In some species, other members of the same species—usually close relatives of the breeding pair , such as offspring from previous broods—will help with the raising of the young. Such alloparenting is particularly common among the Corvida , which includes such birds as the true crows , Australian magpie and fairy-wrens , but has been observed in species as different as the rifleman and red kite . Among most groups of animals, male parental care is rare. In birds, however, it is quite common—more so than in any other vertebrate class. Although territory and nest site defence, incubation, and chick feeding are often shared tasks, there is sometimes a division of labour in which one mate undertakes all or most of a particular duty. The point at which chicks fledge varies dramatically. The chicks of the Synthliboramphus murrelets, like the ancient murrelet , leave the nest the night after they hatch, following their parents out to sea, where they are raised away from terrestrial predators. Some other species, such as ducks, move their chicks away from the nest at an early age. In most species, chicks leave the nest just before, or soon after, they are able to fly. The amount of parental care after fledging varies; albatross chicks leave the nest on their own and receive no further help, while other species continue some supplementary feeding after fledging. Chicks may also follow their parents during their first migration . Brood parasitism , in which an egg-layer leaves her eggs with another individual's brood, is more common among birds than any other type of organism. After a parasitic bird lays her eggs in another bird's nest, they are often accepted and raised by the host at the expense of the host's own brood. Brood parasites may be either obligate brood parasites , which must lay their eggs in the nests of other species because they are incapable of raising their own young, or non-obligate brood parasites , which sometimes lay eggs in the nests of conspecifics to increase their reproductive output even though they could have raised their own young. One hundred bird species, including honeyguides , icterids , and ducks , are obligate parasites, though the most famous are the cuckoos . Some brood parasites are adapted to hatch before their host's young, which allows them to destroy the host's eggs by pushing them out of the nest or to kill the host's chicks; this ensures that all food brought to the nest will be fed to the parasitic chicks. Birds have evolved a variety of mating behaviours, with the peacock tail being perhaps the most famous example of sexual selection and the Fisherian runaway . Commonly occurring sexual dimorphisms such as size and colour differences are energetically costly attributes that signal competitive breeding situations. Many types of avian sexual selection have been identified; intersexual selection, also known as female choice; and intrasexual competition, where individuals of the more abundant sex compete with each other for the privilege to mate. Sexually selected traits often evolve to become more pronounced in competitive breeding situations until the trait begins to limit the individual's fitness. Conflicts between an individual fitness and signalling adaptations ensure that sexually selected ornaments such as plumage colouration and courtship behaviour are "honest" traits. Signals must be costly to ensure that only good-quality individuals can present these exaggerated sexual ornaments and behaviours. Inbreeding causes early death ( inbreeding depression ) in the zebra finch Taeniopygia guttata . Embryo survival (that is, hatching success of fertile eggs) was significantly lower for sib-sib mating pairs than for unrelated pairs. Darwin's finch Geospiza scandens experiences inbreeding depression (reduced survival of offspring) and the magnitude of this effect is influenced by environmental conditions such as low food availability. Incestuous matings by the purple-crowned fairy wren Malurus coronatus result in severe fitness costs due to inbreeding depression (greater than 30% reduction in hatchability of eggs). Females paired with related males may undertake extra pair matings (see Promiscuity#Other animals for 90% frequency in avian species) that can reduce the negative effects of inbreeding. However, there are ecological and demographic constraints on extra pair matings. Nevertheless, 43% of broods produced by incestuously paired females contained extra pair young. Inbreeding depression occurs in the great tit ( Parus major ) when the offspring produced as a result of a mating between close relatives show reduced fitness. In natural populations of Parus major , inbreeding is avoided by dispersal of individuals from their birthplace, which reduces the chance of mating with a close relative. Southern pied babblers Turdoides bicolor appear to avoid inbreeding in two ways. The first is through dispersal, and the second is by avoiding familiar group members as mates. Cooperative breeding in birds typically occurs when offspring, usually males, delay dispersal from their natal group in order to remain with the family to help rear younger kin. Female offspring rarely stay at home, dispersing over distances that allow them to breed independently, or to join unrelated groups. In general, inbreeding is avoided because it leads to a reduction in progeny fitness ( inbreeding depression ) due largely to the homozygous expression of deleterious recessive alleles. Cross-fertilisation between unrelated individuals ordinarily leads to the masking of deleterious recessive alleles in progeny. Birds occupy a wide range of ecological positions. While some birds are generalists, others are highly specialised in their habitat or food requirements. Even within a single habitat, such as a forest, the niches occupied by different species of birds vary, with some species feeding in the forest canopy , others beneath the canopy, and still others on the forest floor. Forest birds may be insectivores , frugivores , or nectarivores . Aquatic birds generally feed by fishing, plant eating, and piracy or kleptoparasitism . Many grassland birds are granivores. Birds of prey specialise in hunting mammals or other birds, while vultures are specialised scavengers . Birds are also preyed upon by a range of mammals including a few avivorous bats. A wide range of endo- and ectoparasites depend on birds and some parasites that are transmitted from parent to young have co-evolved and show host-specificity. Some nectar-feeding birds are important pollinators, and many frugivores play a key role in seed dispersal. Plants and pollinating birds often coevolve , and in some cases a flower's primary pollinator is the only species capable of reaching its nectar. Birds are often important to island ecology. Birds have frequently reached islands that mammals have not; on those islands, birds may fulfil ecological roles typically played by larger animals. For example, in New Zealand nine species of moa were important browsers, as are the kererÅ« and kokako today. Today the plants of New Zealand retain the defensive adaptations evolved to protect them from the extinct moa. Many birds act as ecosystem engineers through the construction of nests, which provide important microhabitats and food for hundreds of species of invertebrates. Nesting seabirds may affect the ecology of islands and surrounding seas, principally through the concentration of large quantities of guano , which may enrich the local soil and the surrounding seas. A wide variety of avian ecology field methods , including counts, nest monitoring, and capturing and marking, are used for researching avian ecology. Since birds are highly visible and common animals, humans have had a relationship with them since the dawn of man. Sometimes, these relationships are mutualistic , like the cooperative honey-gathering among honeyguides and African peoples such as the Borana . Other times, they may be commensal , as when species such as the house sparrow have benefited from human activities. Several species have reconciled to habits of farmers who practice traditional farming. Examples include the Sarus Crane that begins nesting in India when farmers flood the fields in anticipation of rains, and the Woolly-necked Storks that have taken to nesting on a short tree grown for agroforestry beside fields and canals. Several bird species have become commercially significant agricultural pests, and some pose an aviation hazard . Human activities can also be detrimental, and have threatened numerous bird species with extinction ( hunting , avian lead poisoning , pesticides , roadkill , wind turbine kills and predation by pet cats and dogs are common causes of death for birds). Birds can act as vectors for spreading diseases such as psittacosis , salmonellosis , campylobacteriosis , mycobacteriosis (avian tuberculosis ), avian influenza (bird flu), giardiasis , and cryptosporidiosis over long distances. Some of these are zoonotic diseases that can also be transmitted to humans. Domesticated birds raised for meat and eggs, called poultry , are the largest source of animal protein eaten by humans; in 2003, 76 million tons of poultry and 61 million tons of eggs were produced worldwide. Chickens account for much of human poultry consumption, though domesticated turkeys , ducks , and geese are also relatively common. Many species of birds are also hunted for meat. Bird hunting is primarily a recreational activity except in extremely undeveloped areas. The most important birds hunted in North and South America are waterfowl; other widely hunted birds include pheasants , wild turkeys , quail, doves , partridge , grouse , snipe , and woodcock . [ citation needed ] Muttonbirding is also popular in Australia and New Zealand. Although some hunting, such as that of muttonbirds, may be sustainable, hunting has led to the extinction or endangerment of dozens of species. Other commercially valuable products from birds include feathers (especially the down of geese and ducks), which are used as insulation in clothing and bedding, and seabird faeces ( guano ), which is a valuable source of phosphorus and nitrogen. The War of the Pacific , sometimes called the Guano War, was fought in part over the control of guano deposits. Birds have been domesticated by humans both as pets and for practical purposes. Colourful birds, such as parrots and mynas , are bred in captivity or kept as pets, a practice that has led to the illegal trafficking of some endangered species . Falcons and cormorants have long been used for hunting and fishing , respectively. Messenger pigeons , used since at least 1 AD, remained important as recently as World War II . Today, such activities are more common either as hobbies, for entertainment and tourism, Amateur bird enthusiasts (called birdwatchers, twitchers or, more commonly, birders ) number in the millions. Many homeowners erect bird feeders near their homes to attract various species. Bird feeding has grown into a multimillion-dollar industry; for example, an estimated 75% of households in Britain provide food for birds at some point during the winter. Birds play prominent and diverse roles in religion and mythology. In religion, birds may serve as either messengers or priests and leaders for a deity , such as in the Cult of Makemake , in which the Tangata manu of Easter Island served as chiefs or as attendants, as in the case of Hugin and Munin , the two common ravens who whispered news into the ears of the Norse god Odin . In several civilisations of ancient Italy , particularly Etruscan and Roman religion , priests were involved in augury , or interpreting the words of birds while the "auspex" (from which the word "auspicious" is derived) watched their activities to foretell events. They may also serve as religious symbols , as when Jonah ( Hebrew : ×™×•× ×” , dove ) embodied the fright, passivity, mourning, and beauty traditionally associated with doves. Birds have themselves been deified, as in the case of the common peacock , which is perceived as Mother Earth by the people of southern India. In the ancient world, doves were used as symbols of the Mesopotamian goddess Inanna (later known as Ishtar), the Canaanite mother goddess Asherah , and the Greek goddess Aphrodite . In ancient Greece , Athena , the goddess of wisdom and patron deity of the city of Athens , had a little owl as her symbol . In religious images preserved from the Inca and Tiwanaku empires, birds are depicted in the process of transgressing boundaries between earthly and underground spiritual realms. Indigenous peoples of the central Andes maintain legends of birds passing to and from metaphysical worlds. Birds have featured in culture and art since prehistoric times, when they were represented in early cave painting and carvings. Some birds have been perceived as monsters, including the mythological Roc and the Māori 's legendary Pouākai , a giant bird capable of snatching humans. Birds were later used as symbols of power, as in the magnificent Peacock Throne of the Mughal and Persian emperors. With the advent of scientific interest in birds, many paintings of birds were commissioned for books. [ citation needed ] Among the most famous of these bird artists was John James Audubon , whose paintings of North American birds were a great commercial success in Europe and who later lent his name to the National Audubon Society . Birds are also important figures in poetry; for example, Homer incorporated nightingales into his Odyssey , and Catullus used a sparrow as an erotic symbol in his Catullus 2 . The relationship between an albatross and a sailor is the central theme of Samuel Taylor Coleridge 's The Rime of the Ancient Mariner , which led to the use of the term as a metaphor for a 'burden' . Other English metaphors derive from birds; vulture funds and vulture investors, for instance, take their name from the scavenging vulture. Aircraft, particularly military aircraft, are frequently named after birds. The predatory nature of raptors make them popular choices for fighter aircraft such as the F-16 Fighting Falcon and the Harrier Jump Jet , while the names of seabirds may be chosen for aircraft primarily used by naval forces such as the HU-16 Albatross and the V-22 Osprey . Perceptions of bird species vary across cultures. Owls are associated with bad luck, witchcraft , and death in parts of Africa, but are regarded as wise across much of Europe. Hoopoes were considered sacred in Ancient Egypt and symbols of virtue in Persia , but were thought of as thieves across much of Europe and harbingers of war in Scandinavia . In heraldry , birds, especially eagles , often appear in coats of arms In vexillology , birds are a popular choice on flags . Birds feature in the flag designs of 17 countries and numerous subnational entities and territories. Birds are used by nations to symbolise a country's identity and heritage, with 91 countries officially recognising a national bird . Birds of prey are highly represented, though some nations have chosen other species of birds with parrots being popular among smaller, tropical nations. In music , birdsong has influenced composers and musicians in several ways: they can be inspired by birdsong; they can intentionally imitate bird song in a composition, as Vivaldi , Messiaen , and Beethoven did, along with many later composers; they can incorporate recordings of birds into their works, as Ottorino Respighi first did; or like Beatrice Harrison and David Rothenberg , they can duet with birds. A 2023 archaeological excavation of a 10000-year-old site in Israel yielded hollow wing bones of coots and ducks with perforations made on the side that are thought to have allowed them to be used as flutes or whistles possibly used by Natufian people to lure birds of prey. Domesticated birds raised for meat and eggs, called poultry , are the largest source of animal protein eaten by humans; in 2003, 76 million tons of poultry and 61 million tons of eggs were produced worldwide. Chickens account for much of human poultry consumption, though domesticated turkeys , ducks , and geese are also relatively common. Many species of birds are also hunted for meat. Bird hunting is primarily a recreational activity except in extremely undeveloped areas. The most important birds hunted in North and South America are waterfowl; other widely hunted birds include pheasants , wild turkeys , quail, doves , partridge , grouse , snipe , and woodcock . [ citation needed ] Muttonbirding is also popular in Australia and New Zealand. Although some hunting, such as that of muttonbirds, may be sustainable, hunting has led to the extinction or endangerment of dozens of species. Other commercially valuable products from birds include feathers (especially the down of geese and ducks), which are used as insulation in clothing and bedding, and seabird faeces ( guano ), which is a valuable source of phosphorus and nitrogen. The War of the Pacific , sometimes called the Guano War, was fought in part over the control of guano deposits. Birds have been domesticated by humans both as pets and for practical purposes. Colourful birds, such as parrots and mynas , are bred in captivity or kept as pets, a practice that has led to the illegal trafficking of some endangered species . Falcons and cormorants have long been used for hunting and fishing , respectively. Messenger pigeons , used since at least 1 AD, remained important as recently as World War II . Today, such activities are more common either as hobbies, for entertainment and tourism, Amateur bird enthusiasts (called birdwatchers, twitchers or, more commonly, birders ) number in the millions. Many homeowners erect bird feeders near their homes to attract various species. Bird feeding has grown into a multimillion-dollar industry; for example, an estimated 75% of households in Britain provide food for birds at some point during the winter. Birds play prominent and diverse roles in religion and mythology. In religion, birds may serve as either messengers or priests and leaders for a deity , such as in the Cult of Makemake , in which the Tangata manu of Easter Island served as chiefs or as attendants, as in the case of Hugin and Munin , the two common ravens who whispered news into the ears of the Norse god Odin . In several civilisations of ancient Italy , particularly Etruscan and Roman religion , priests were involved in augury , or interpreting the words of birds while the "auspex" (from which the word "auspicious" is derived) watched their activities to foretell events. They may also serve as religious symbols , as when Jonah ( Hebrew : ×™×•× ×” , dove ) embodied the fright, passivity, mourning, and beauty traditionally associated with doves. Birds have themselves been deified, as in the case of the common peacock , which is perceived as Mother Earth by the people of southern India. In the ancient world, doves were used as symbols of the Mesopotamian goddess Inanna (later known as Ishtar), the Canaanite mother goddess Asherah , and the Greek goddess Aphrodite . In ancient Greece , Athena , the goddess of wisdom and patron deity of the city of Athens , had a little owl as her symbol . In religious images preserved from the Inca and Tiwanaku empires, birds are depicted in the process of transgressing boundaries between earthly and underground spiritual realms. Indigenous peoples of the central Andes maintain legends of birds passing to and from metaphysical worlds. Birds have featured in culture and art since prehistoric times, when they were represented in early cave painting and carvings. Some birds have been perceived as monsters, including the mythological Roc and the Māori 's legendary Pouākai , a giant bird capable of snatching humans. Birds were later used as symbols of power, as in the magnificent Peacock Throne of the Mughal and Persian emperors. With the advent of scientific interest in birds, many paintings of birds were commissioned for books. [ citation needed ] Among the most famous of these bird artists was John James Audubon , whose paintings of North American birds were a great commercial success in Europe and who later lent his name to the National Audubon Society . Birds are also important figures in poetry; for example, Homer incorporated nightingales into his Odyssey , and Catullus used a sparrow as an erotic symbol in his Catullus 2 . The relationship between an albatross and a sailor is the central theme of Samuel Taylor Coleridge 's The Rime of the Ancient Mariner , which led to the use of the term as a metaphor for a 'burden' . Other English metaphors derive from birds; vulture funds and vulture investors, for instance, take their name from the scavenging vulture. Aircraft, particularly military aircraft, are frequently named after birds. The predatory nature of raptors make them popular choices for fighter aircraft such as the F-16 Fighting Falcon and the Harrier Jump Jet , while the names of seabirds may be chosen for aircraft primarily used by naval forces such as the HU-16 Albatross and the V-22 Osprey . Perceptions of bird species vary across cultures. Owls are associated with bad luck, witchcraft , and death in parts of Africa, but are regarded as wise across much of Europe. Hoopoes were considered sacred in Ancient Egypt and symbols of virtue in Persia , but were thought of as thieves across much of Europe and harbingers of war in Scandinavia . In heraldry , birds, especially eagles , often appear in coats of arms In vexillology , birds are a popular choice on flags . Birds feature in the flag designs of 17 countries and numerous subnational entities and territories. Birds are used by nations to symbolise a country's identity and heritage, with 91 countries officially recognising a national bird . Birds of prey are highly represented, though some nations have chosen other species of birds with parrots being popular among smaller, tropical nations. In music , birdsong has influenced composers and musicians in several ways: they can be inspired by birdsong; they can intentionally imitate bird song in a composition, as Vivaldi , Messiaen , and Beethoven did, along with many later composers; they can incorporate recordings of birds into their works, as Ottorino Respighi first did; or like Beatrice Harrison and David Rothenberg , they can duet with birds. A 2023 archaeological excavation of a 10000-year-old site in Israel yielded hollow wing bones of coots and ducks with perforations made on the side that are thought to have allowed them to be used as flutes or whistles possibly used by Natufian people to lure birds of prey. Human activities have caused population decreases or extinction in many bird species. Over a hundred bird species have gone extinct in historical times, although the most dramatic human-caused avian extinctions, eradicating an estimated 750–1800 species, occurred during the human colonisation of Melanesian , Polynesian , and Micronesian islands. Many bird populations are declining worldwide, with 1,227 species listed as threatened by BirdLife International and the IUCN in 2009. The most commonly cited human threat to birds is habitat loss . Other threats include overhunting, accidental mortality due to collisions with buildings or vehicles , long-line fishing bycatch , pollution (including oil spills and pesticide use), competition and predation from nonnative invasive species , and climate change . Governments and conservation groups work to protect birds, either by passing laws that preserve and restore bird habitat or by establishing captive populations for reintroductions. Such projects have produced some successes; one study estimated that conservation efforts saved 16 species of bird that would otherwise have gone extinct between 1994 and 2004, including the California condor and Norfolk parakeet . Human activities have allowed the expansion of a few temperate area species, such as the barn swallow and European starling . In the tropics and sub-tropics, relatively more species are expanding due to human activities, particularly due to the spread of crops such as rice whose expansion in south Asia has benefitted at least 64 bird species, though may have harmed many more species.

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Avian influenza

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Influenza C virus

Influenza C virus is the only species in the genus Gammainfluenzavirus , in the virus family Orthomyxoviridae , which like other influenza viruses, causes influenza . Influenza C viruses are known to infect humans and pigs . Flu due to the Type C species is rare compared with Types B or A, but can be severe and can cause local epidemics . Type C has 7 RNA segments and encodes 9 proteins , while Types A and B have 8 RNA segments and encode at least 10 proteins. [ citation needed ]Influenza viruses are members of the family Orthomyxoviridae . Influenza viruses A, B, C, and D represent the four antigenic types of influenza viruses. Of the four antigenic types, influenza A virus is the most severe, influenza B virus is less severe but can still cause outbreaks, and influenza C virus is usually only associated with minor symptoms. Influenza D virus is 50% similar in amino acid composition to influenza C virus, similar to the level of divergence between types A and B, while types C and D have a much greater level of divergence from types A and B. Influenza viruses C and D were estimated to have diverged from a common ancestor over 1,500 years ago, around 482 AD. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. Influenza A virus can infect a variety of animals as well as humans, and its natural reservoir (natural host) is birds, whereas influenza viruses B, C, and D do not have animal reservoirs . Influenza C virus is not as easily isolated so less information is known of this type, but studies show that it occurs worldwide. Influenza C virus currently has six lineages, which were estimated to have emerged around 1896 AD. Metatranscriptomics studies also have identified closely related "Influenza C and D-like" viruses in several amphibian and fish species suggesting the potential for divergent influenza C/D like viruses circulating in aquatic systems. This virus may be spread from person to person through respiratory droplets or by fomites (non-living material) due to its ability to survive on surfaces for short durations. As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. Influenza viruses have a relatively short incubation period (lapse of time from exposure to pathogen to the appearance of symptoms) of 18–72 hours and infect the epithelial cells of the respiratory tract . Influenza virus C tends to cause mild upper respiratory infections . Cold-like symptoms are associated with the virus including fever (38–40 °C), dry cough, rhinorrhea (nasal discharge), headache, muscle pain, and achiness. The virus may lead to more severe infections such as bronchitis and pneumonia . After an individual becomes infected, the immune system develops antibodies against that infectious agent. This is the body's main source of protection. Most children between five and ten years old have already produced antibodies for influenza virus C. As with all influenza viruses, type C affects individuals of all ages but is most severe in young children, the elderly and individuals with underlying health problems. Young children have less prior exposure and have not developed the antibodies and the elderly have less effective immune systems. Influenza virus infections have one of the highest preventable mortalities in many countries of the world. Influenza viruses, like all viruses in the family Orthomyxoviridae, are enveloped RNA viruses with single stranded negative sense RNA genomes . Divergent evolution of the matrix protein (M1) and nucleoprotein (NP), are used to determine if the virus is type A, B, C, or D. The M1 protein is required for virus assembly and NP functions in transcription and replication . These viruses also contain proteins on the surface of the cell membrane called glycoproteins. Type A and B have two glycoproteins : hemagglutinin (HA) and neuraminidase (NA). Type A is divided into subtypes based on distinct differences in the types of these glycoproteins. Types C and D have only one glycoprotein: hemagglutinin-esterase fusion (HEF). These glycoproteins allow for attachment and fusion of viral and cellular membranes. Fusion of these membranes allows the viral proteins and genome to be released into the host cell, which then causes the infection. Types C and D are the only influenza viruses to express the enzyme esterase . This enzyme is similar to the enzyme neuraminidase produced by Types A and B in that they both function in destroying the host cell receptors. Glycoproteins may undergo mutations (antigenic drift) or reassortment in which a new type of HA or NA is produced (antigenic shift). Influenza virus C is only capable of antigenic drift whereas Type A undergoes antigenic shift , as well. When either of these processes occur, the antibodies formed by the immune system no longer protect against these altered glycoproteins . Because of this, viruses continually cause infections. Influenza virus C is different from Types A and B in its growth requirements. Because of this, it is not isolated and identified as frequently. Diagnosis is by virus isolation, serology , and other tests. Hemagglutination inhibition (HI) is one method of serology that detects antibodies for diagnostic purposes. Western blot (immunoblot assay) and enzyme-linked immunosorbent assay ( ELISA ) are two other methods used to detect proteins (or antigens) in serum. In each of these techniques, the antibodies for the protein of interest are added and the presence of the specific protein is indicated by a color change. ELISA was shown to have higher sensitivity to the HEF than the HI test. Because only Influenza viruses C and D produce esterase, In Situ Esterase Assays provide a quick and inexpensive method of detecting just Types C and D. If more individuals were tested for Influenza virus C as well as the other three types, infections not previously associated with Type C may be recognized. Because influenza virus A has an animal reservoir that contains all the known subtypes and can undergo antigenic shift , this type of influenza virus is capable of producing pandemics . Influenza viruses A and B also cause seasonal epidemics almost every year due to their ability to antigenic drift . Influenza virus C does not have this capability and it is not thought to be a significant concern for human health. Therefore, there are no vaccinations against influenza virus C.

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Avian influenza

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Influenza A virus subtype H1N2

Influenza A virus subtype H1N2 (A/H1N2) is a subtype of the species Influenza A virus (sometimes called bird flu or swine flu ). It is currently endemic in pig populations and is occasionally seen in humans . The virus does not cause more severe illness than other influenza viruses, and no unusual increases in influenza activity have been associated with it. Between December 1988 and March 1989, 19 influenza H1N2 virus isolates were identified in 6 cities in China , but the virus did not spread further. A(H1N2) was identified during the 2001–02 flu season (northern hemisphere) in Canada, the U.S., Ireland , Latvia , France, Romania , Oman , India, Malaysia , and Singapore with earliest documented outbreak of the virus occurring in India on May 31, 2001. [ citation needed ] On February 6, 2002, the World Health Organization (WHO) in Geneva and the Public Health Laboratory Service (PHLS) in the United Kingdom reported the identification influenza A(H1N2) virus from humans in the UK , Israel , and Egypt [ citation needed ] . The 2001–02 Influenza A(H1N2) Wisconsin strain appears to have resulted from the reassortment of the genes of the currently circulating influenza A( H1N1 ) and A( H3N2 ) subtypes. [ citation needed ] In March 2018 a single case of H1N2 was identified in a 19-month-old in the Netherlands. In January 2019 a single case of H1N2 was identified in Sweden. Because the hemagglutinin protein of the virus is similar to that of the currently [ when? ] circulating A(H1N1) viruses and the neuraminidase protein is similar to that of the current A(H3N2) viruses , the seasonal flu vaccine should provide good protection against influenza virus as well as protection against the currently circulating seasonal A(H1N1), A(H3N2), and B viruses. [ citation needed ] In October 2020, a case of the H1N2 variant H1N2v was confirmed in Alberta, Canada and was the first confirmed human case in the country. In September 2021, a case was found in France. In November 2023 a case was found in the UK.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/2015_United_States_H5N2_outbreak/html

2015 United States H5N2 outbreak

In 2015, an outbreak of avian influenza subtype H5N2 was identified in a series of chicken and turkey farming operations in the Midwestern United States . By May 30, more than 43 million birds in 15 states had been destroyed as a result of the outbreak, including nearly 30 million in Iowa alone, the nation's largest egg producer. In the Midwestern U.S., the average price of eggs had increased 120% between April 22 and May 30. The effects however were seen nationwide, with prices in California up 71% in the same timeframe. The virus was first identified in Minnesota in early March. Prior to April 20, it affected commercial turkey farms almost exclusively, in the states of Arkansas , Iowa , Missouri , North Dakota , South Dakota , Wisconsin , and at 28 farms in Minnesota, where the virus was initially identified. [ citation needed ] Migratory waterfowl are assumed to have brought the disease to the Midwest, but how it made its way into poultry barns is undetermined. No human cases have been reported, and human infection is almost impossible. [ citation needed ]On Monday, April 20, the U.S. Department of Agriculture announced that 5.3 million egg-producing hens at a northwest Iowa farm must be destroyed after the virus was confirmed. The number at this operation alone comprised a little over 1% of egg-laying hens in the United States. This infection would be the first in a series at large hen operations in Iowa, Nebraska , and other states. [ citation needed ] As of May 27, over 25 million chickens had either died of the infection or been euthanized in Iowa alone. Nebraska's toll at the same date was 7 million—a majority of the state's 9.45 million egg-laying hens. This table shows large bird farm infections during the 2015 outbreak. All birds affected either died of the H5N2 infection itself, or were destroyed as a precautionary measure. While 205 total infections were confirmed through June 1, only larger outbreaks (affecting >200,000 hens or >50,000 turkeys) are displayed here.This table shows large bird farm infections during the 2015 outbreak. All birds affected either died of the H5N2 infection itself, or were destroyed as a precautionary measure. While 205 total infections were confirmed through June 1, only larger outbreaks (affecting >200,000 hens or >50,000 turkeys) are displayed here.When an infection was confirmed, all birds at the affected farm were destroyed per USDA guidelines. The birds were often culled by foam depopulation through pumping an expanding water-based foam into the barn houses, which suffocates them within minutes. The birds were then composted, usually at the location.

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Avian influenza

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New normal

A new normal is a state to which an economy, society, etc. settles following a crisis, when this differs from the situation that prevailed prior to the start of the crisis (the "old normal"). The term has been employed retroactively in relation to World War I , the September 11 attacks , the financial crisis of 2007–2008 , the aftermath of the Great Recession , the COVID-19 pandemic and other events. In 1918, Henry A. Wise Wood posted a dilemma , To consider the problems before us we must divide our epoch into three periods, that of war, that of transition, that of the new normal, which undoubtedly will supersede the old. The questions before us, therefore, are, broadly, two: How shall we pass from war to the new normal with the least jar, in the shortest time? In that respect should the new normal be shaped to differ from the old? The phrase was extensively used by Roger McNamee in his 2003 interview to Fast Company while describing the new normal in technology development in regards to business and finance after the dot-com bubble bust, Forget about the Next Big Thing, the next thing has started. It's called the New Normal, and 2003 will be the first full year of it. The New Normal isn't where you wait for the next boom. It's about the rest of your life. ... There was so much urgency that every standard — for due diligence, leadership, recruiting, and investment — was relaxed. The New Normal is about real life — and real time. Getting things right the first time is more important than getting things done quickly. The phrase was used in 2005 by Peter M. Sandman and Jody Lanard in relation to methods of manipulation of attitudes of the public towards avian influenza. They explained that the initial, typically temporary, fearfulness of a novel risk such as a flu pandemic is something to be guided, that this initial period is a "teachable moment" and offers the opportunity of establishing a "new normal". The phrase was used in the context of cautioning the belief of economists and policy makers that industrial economies would revert to their most recent means post the 2007–2008 financial crisis. The 29 January 2009 edition of the Philadelphia City Paper quoted Paul Glover referring to the need for "new normals" in community development, when introducing his cover story "Prepare for the Best". The 2010 Per Jacobsson lecture delivered by Mohamed A. El-Erian at the International Monetary Fund , was titled "Navigating the New Normal in Industrial Countries". In the lecture El-Erian stated that "Our use of the term was an attempt to move the discussion beyond the notion that the crisis was a mere flesh wound...instead the crisis cut to the bone. It was the inevitable result of an extraordinary, multiyear period which was anything but normal". El-Erian's lecture cites a 18 May 2008 Bloomberg News article written by journalists Rich Miller and Matthew Benjamin for first using the term: "Post-Subprime Economy Means Subpar Growth as New Normal in U.S." The phrase has subsequently been used by ABC News , BBC News , the New York Times , and formed part of a question by Candy Crowley , the moderator of the Second U.S. presidential debate of 2012 . Since 2012, China's economy has shown a marked slowdown, with growth rates declining from double digit levels (before the 2007-2009 financial crisis) to around 7% in 2014. In 2014, a statement by Xi Jinping , General Secretary of the Chinese Communist Party , indicated that China was entering a 'new normal' ( Chinese : 新常态 ). This term was subsequently popularised by the press and came to refer to expectations of 7% growth rates in China for the foreseeable future. It was indicative of the Chinese government's anticipation of moderate but perhaps more stable economic growth in the medium-to-long term. During the earlier parts of the COVID-19 pandemic , the term new normal was used to refer to changes in human behavior during the pandemic or speculated changes after the pandemic. In May 2020, physicians at the University of Kansas Health System predicted that daily life for most people would change during the pandemic after the lifting of lockdowns. This would include limiting person-to-person contact, like handshakes and hugs, as well as maintaining distance from others, known as social distancing . They predicted things would change again after vaccines became available. In Europe, the term "new normal", first conceptualized in 2018 by Austrian philosopher and political scholar Paul Sailer-Wlasits, has become a popular buzzword in contemporary politics. Initially introduced in the German-speaking world, Paul Sailer-Wlasits associated the term with various phenomena, including political populism and the 45th U.S. administration under Donald Trump, which he critically dubbed the "new global normal". Since then, the phrase has gained traction among politicians in Austria, Germany, and Spain. In Austria, Chancellor Sebastian Kurz incorporated the term into his rhetoric typically based on a few catchy buzzwords from mid-April 2020, establishing it as a new political buzzword. The Austrian media reacted critically to this, questioning whether this was intended to convey a permanent erosion of civil liberties. In 1918, Henry A. Wise Wood posted a dilemma , To consider the problems before us we must divide our epoch into three periods, that of war, that of transition, that of the new normal, which undoubtedly will supersede the old. The questions before us, therefore, are, broadly, two: How shall we pass from war to the new normal with the least jar, in the shortest time? In that respect should the new normal be shaped to differ from the old? The phrase was extensively used by Roger McNamee in his 2003 interview to Fast Company while describing the new normal in technology development in regards to business and finance after the dot-com bubble bust, Forget about the Next Big Thing, the next thing has started. It's called the New Normal, and 2003 will be the first full year of it. The New Normal isn't where you wait for the next boom. It's about the rest of your life. ... There was so much urgency that every standard — for due diligence, leadership, recruiting, and investment — was relaxed. The New Normal is about real life — and real time. Getting things right the first time is more important than getting things done quickly. The phrase was used in 2005 by Peter M. Sandman and Jody Lanard in relation to methods of manipulation of attitudes of the public towards avian influenza. They explained that the initial, typically temporary, fearfulness of a novel risk such as a flu pandemic is something to be guided, that this initial period is a "teachable moment" and offers the opportunity of establishing a "new normal". The phrase was used in the context of cautioning the belief of economists and policy makers that industrial economies would revert to their most recent means post the 2007–2008 financial crisis. The 29 January 2009 edition of the Philadelphia City Paper quoted Paul Glover referring to the need for "new normals" in community development, when introducing his cover story "Prepare for the Best". The 2010 Per Jacobsson lecture delivered by Mohamed A. El-Erian at the International Monetary Fund , was titled "Navigating the New Normal in Industrial Countries". In the lecture El-Erian stated that "Our use of the term was an attempt to move the discussion beyond the notion that the crisis was a mere flesh wound...instead the crisis cut to the bone. It was the inevitable result of an extraordinary, multiyear period which was anything but normal". El-Erian's lecture cites a 18 May 2008 Bloomberg News article written by journalists Rich Miller and Matthew Benjamin for first using the term: "Post-Subprime Economy Means Subpar Growth as New Normal in U.S." The phrase has subsequently been used by ABC News , BBC News , the New York Times , and formed part of a question by Candy Crowley , the moderator of the Second U.S. presidential debate of 2012 . Since 2012, China's economy has shown a marked slowdown, with growth rates declining from double digit levels (before the 2007-2009 financial crisis) to around 7% in 2014. In 2014, a statement by Xi Jinping , General Secretary of the Chinese Communist Party , indicated that China was entering a 'new normal' ( Chinese : 新常态 ). This term was subsequently popularised by the press and came to refer to expectations of 7% growth rates in China for the foreseeable future. It was indicative of the Chinese government's anticipation of moderate but perhaps more stable economic growth in the medium-to-long term.During the earlier parts of the COVID-19 pandemic , the term new normal was used to refer to changes in human behavior during the pandemic or speculated changes after the pandemic. In May 2020, physicians at the University of Kansas Health System predicted that daily life for most people would change during the pandemic after the lifting of lockdowns. This would include limiting person-to-person contact, like handshakes and hugs, as well as maintaining distance from others, known as social distancing . They predicted things would change again after vaccines became available. In Europe, the term "new normal", first conceptualized in 2018 by Austrian philosopher and political scholar Paul Sailer-Wlasits, has become a popular buzzword in contemporary politics. Initially introduced in the German-speaking world, Paul Sailer-Wlasits associated the term with various phenomena, including political populism and the 45th U.S. administration under Donald Trump, which he critically dubbed the "new global normal". Since then, the phrase has gained traction among politicians in Austria, Germany, and Spain. In Austria, Chancellor Sebastian Kurz incorporated the term into his rhetoric typically based on a few catchy buzzwords from mid-April 2020, establishing it as a new political buzzword. The Austrian media reacted critically to this, questioning whether this was intended to convey a permanent erosion of civil liberties. Some commentators objected of overuse and misuse of the phrase by the media while describing atypical situations or behaviors, which turned it into a cliché . Sociological research has also shown this terminology does not adequately capture societal shifts that occur during times of major disruption, such as the COVID-19 pandemic. Citizens, requests may reach you through your comrade neighbors. I hope you will comply willingly; it will speed the day when I can bow out and life can get back to normal — a new normal, free of the Authority, free of guards, free of troops stationed on us, free of passports and searches and arbitrary arrests.

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Avian influenza

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Influenza D virus

Influenza D virus is a species in the virus genus Deltainfluenzavirus , in the family Orthomyxoviridae , that causes influenza . Influenza D viruses are known to infect pigs and cattle ; no human infections from this virus have been observed. First isolated from pigs in 2011, the virus was categorized as a new genus of Orthomyxoviridae in 2016, distinct from the previously-known Influenzavirus C genus; before then, Influenza D virus was thought to be a subtype of Influenzavirus C. Cases of infections from the Type D virus are rare compared to Types A, B, and C. Similar to Type C, Type D has 7 RNA segments and encodes 9 proteins, while Types A and B have 8 RNA segments and encode at least 10 proteins. The influenza viruses are members of the family Orthomyxoviridae . Influenza viruses A, B, C, and D represent the four antigenic types of influenza viruses. Of the four antigenic types, influenza A virus is the most severe, influenza B virus is less severe but can still cause outbreaks, and influenza C virus is usually only associated with minor symptoms. Influenzavirus D is less common than the other antigenic types, and it is not known to cause any human infections. No samples of influenza D virus were detected in serum samples from humans; however, hemagglutination-inhibiting antibodies against influenza D virus have been detected in humans, with an estimated occurrence of 1.3% in the general population, suggesting that this virus may infect humans as well. However, those antibodies may have been produced after an infection by influenza C virus, the antibodies for which cross-react with the Type D virus. More studies are needed to conclude whether or not the Type D virus can infect humans. Influenza D virus is 50% similar in amino acid composition to influenza C virus , similar to the level of divergence between types A and B, while types C and D have a much greater level of divergence from types A and B. Influenzaviruses C and D were estimated to have diverged from a single ancestor over 1,500 years ago, around 482 AD. Influenzavirus D itself currently has two lineages, which were estimated to have emerged over 45 years ago, around 1972 AD. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the ancestor of influenza viruses A and B and the ancestor of influenza viruses C and D are estimated to have diverged from a common ancestor around 8,000 years ago. Metatranscriptomics studies have also identified closely related "Influenza C and D-like" viruses in several amphibian and fish species. Influenza A virus can infect a variety of animals as well as humans, and its natural host or reservoir is birds, whereas influenza viruses B, C, and D do not have animal reservoirs. Influenza viruses C and D are not as easily isolated so less information is known about these types, but studies show that they occur worldwide. This virus may be spread through respiratory droplets or by fomites (non-living material) due to its ability to survive on surfaces for short durations. As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. Influenza viruses have a relatively short incubation period (lapse of time from exposure to pathogen to the appearance of symptoms) of 18–72 hours and infect the epithelial cells of the respiratory tract . In cell culture, influenza D virus has demonstrated an ability to replicate well at 37°C, the normal lung temperature, and can also replicate better and in more types of cells than the Type C virus. This study suggests that influenza D virus may be only a few genetic changes away from being able to invade the lower lung, even though the virus does not actively spread among humans and has a much slower mutation rate than the other influenza viruses. Influenza viruses, like all viruses in the family Orthomyxoviridae, are enveloped RNA viruses with single stranded genomes . The antigens, matrix protein (M1) and nucleoprotein (NP), are used to determine if an influenza virus is type A, B, C, or D. The M1 protein is required for virus assembly and NP functions in transcription and replication . These viruses also contain proteins on the surface of the cell membrane called glycoproteins. Type A and B have two glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Types C and D have only one glycoprotein: hemagglutinin-esterase fusion (HEF). These glycoproteins allow for attachment and fusion of viral and cellular membranes. Fusion of these membranes allows the viral proteins and genome to be released into the host cell, which then causes the infection. Types C and D are the only influenza viruses to express the enzyme esterase. This enzyme is similar to the enzyme neuraminidase produced by Types A and B in that they both function in destroying the host cell receptors. Glycoproteins may undergo mutations (antigenic drift) or reassortment in which a new HA or NA is produced (antigenic shift). Influenza viruses C and D are only capable of antigenic drift whereas Type A undergoes antigenic shift , as well. When either of these processes occur, the antibodies formed by the immune system no longer protect against these altered glycoproteins . Because of this, viruses continually cause infections. Influenza viruses C and D are different from Types A and B in their growth requirements. Because of this, Influenzavirus D is not isolated and identified as frequently. Diagnosis is by virus isolation, serology , and other tests. Hemagglutination inhibition (HI) is one method of serology that detects antibodies for diagnostic purposes. Western blot (immunoblot assay) and enzyme-linked immunosorbent assay ( ELISA ) are two other methods used to detect proteins (or antigens) in serum. In each of these techniques, the antibodies for the protein of interest are added and the presence of the specific protein is indicated by a color change. ELISA was shown to have higher sensitivity to the HEF than the HI test. Because only Influenza viruses C and D produce esterase, In Situ Esterase Assays provide a quick and inexpensive method of detecting just Types C and D. Because influenza virus A has an animal reservoir that contains all the known subtypes and can undergo antigenic shift, this type of influenza virus is capable of producing pandemics . Influenza viruses A and B also cause seasonal epidemics every year due to their ability to antigenic shift. Influenza viruses C and D do not have this capability, and they have not been implicated in any pandemics; thus, there are currently no human vaccines available for Influenza viruses C or D. An inactivated Influenzavirus D vaccine was developed for cattle; however, the vaccine only provided partial protection in challenge experiments.

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Avian influenza

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H5N1 genetic structure

H5N1 genetic structure is the molecular structure of the H5N1 virus's RNA . H5N1 is an Influenza A virus subtype. Experts believe it might mutate into a form that transmits easily from person to person. If such a mutation occurs, it might remain an H5N1 subtype or could shift subtypes as did H2N2 when it evolved into the Hong Kong Flu strain of H3N2 . H5N1 has mutated through antigenic drift into dozens of highly pathogenic varieties, but all currently belonging to genotype Z of avian influenza virus H5N1. Genotype Z emerged through reassortment in 2002 from earlier highly pathogenic genotypes of H5N1 that first appeared in China in 1996 in birds and in Hong Kong in 1997 in humans . The "H5N1 viruses from human infections and the closely related avian viruses isolated in 2004 and 2005 belong to a single genotype, often referred to as genotype Z." This infection of humans coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population. This panzootic (a disease affecting animals of many species especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. The name H5N1 refers to the subtypes of surface antigens present on the virus : hemagglutinin type 5 and neuraminidase type 1. Genotype Z of H5N1 is now the dominant genotype of H5N1. Genotype Z is endemic in birds in southeast Asia and represents a long term pandemic threat. Influenza A viruses have 11 genes on eight separate RNA molecules Orthomyxoviruses : Two of the most important RNA molecules are HA and PB1. HA creates a surface antigen that is especially important in transmissibility . PB1 creates a viral polymerase molecule that is especially important in virulence . The HA RNA molecule contains the HA gene, which codes for hemagglutinin , which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to cells . This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins. One genetic factor in distinguishing between human flu viruses and avian flu viruses is that avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors. Humans have avian-type receptors at very low densities and chickens have human-type receptors at very low densities. Some isolates taken from H5N1-infected human have been observed to have HA mutations at positions 182, 192, 223, 226, or 228 and these mutations have been shown to influence the selective binding of the virus to those previously mentioned sialic acid avian and/or human cell surface receptors. These are the types of mutations that can change a bird flu virus into a flu pandemic virus. A 2008 virulence study that mated in a laboratory an avian flu H5N1 virus that circulated in Thailand in 2004 and a human flu H3N2 virus recovered in Wyoming in 2003 produced 63 viruses representing various potential combinations of human and avian influenza A virus genes. One in five were lethal to mice at low doses. The virus that most closely matched H5N1 for virulence was one with the hemagglutinin (HA), the neuraminidase (NA) and the PB1 avian flu virus RNA molecules with their genes combined with the remaining five RNA molecules (PB2, PA, NP, M, and NS) with their genes from the human flu virus. Both the viruses from the 1957 pandemic and 1968 pandemic carried an avian flu virus PB1 gene. The authors suggest that picking up an avian flu virus PB1 gene may be a critical step in a potential flu pandemic virus arising through reassortment ." PB1 codes for the PB1 protein and the PB1-F2 protein. The PB1 protein is a critical component of the viral polymerase . The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis . [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." This was discovered by Chen et al. and reported in Nature . "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus." The Orthomyxovirus family consists of 7 genera: The "RNA viruses" include the "negative-sense ssRNA viruses" which include the Family "Orthomyxoviridae" which contains five genera, classified by variations in nucleoprotein (NP and M) antigens. One of these is the Genus "Influenzavirus A" which consists of a single species called " Influenza A virus "; one of its subtypes is H5N1 . H5N1 (like the other avian flu viruses) has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent , and mortality rates in infected flocks often approach 100%. LPAI viruses are generally of lower virulence, but these viruses can serve as progenitors to HPAI viruses. The current strain of H5N1 responsible for die-offs of domestic birds in Asia is an HPAI strain; other strains of H5N1 occurring elsewhere in the world are less virulent and, therefore, are classified as LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally a highly pathogenic avian virus is not highly pathogenic to either humans or non-poultry birds. This current strain of H5N1 is unusual in being deadly to so many species. Both "influenza" (meaning flu) and "A" (meaning species type A) can be used as adjectives of the noun "virus" resulting in the noun phrase "influenza A virus"; which when capitalized is the proper noun Influenza A virus which is the name of the species the noun phrase also refers to.A virus is one type of microscopic parasite that infects cells in biological organisms. The Orthomyxoviridae are a family of RNA viruses which infect vertebrates. It includes those viruses which cause influenza . Viruses of this family contain 7 to 8 segments of linear negative-sense single-stranded RNA . "Influenza virus" refers to a subset of Orthomyxoviridae that create influenza . This taxonomic category is not based on phylogenetics . Influenza A viruses have 10 genes on eight separate RNA molecules, which, for the reasons mentioned above, are named PB2, PB1, PA, HA, NP, NA, M, and NS. HA, NA, and M specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies . (An eleventh recently discovered gene called PB1-F2 sometimes creates a protein but is absent from some influenza virus isolates. ) This segmentation of the influenza genome facilitates genetic recombination by segment reassortment in hosts who are infected with two different influenza viruses at the same time. Influenza A virus is the only species in the Influenzavirus A genus of the family Orthomyxoviridae and are negative sense, single-stranded, segmented RNA viruses . "The influenza virus RNA polymerase is a multifunctional complex composed of the three viral proteins PB1, PB2 and PA, which, together with the viral nucleoprotein NP, form the minimum complement required for viral mRNA synthesis and replication." HA codes for hemagglutinin , which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to cells . This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins. One genetic factor in distinguishing between human flu viruses and avian flu viruses is that "avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors." A mutation found in Turkey in 2006 "involves a substitution in one sample of an amino acid at position 223 of the haemoagglutinin receptor protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before — in a father and son in Hong Kong in 2003, and in one fatal case in Vietnam last year. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans." [ according to whom? ] Another mutation in the same sample at position 153 has as yet unknown effects. "Amino acid residues at positions 226 and 228 of the receptor binding pocket of HA appear to determine binding affinity to cell surface receptors and to influence the selective binding of the virus to avian (sialic acid -2,3-NeuAcGal) or human (sialic acid -2,6-NeuAcGal) cell surface receptors. The human A/HK/212/03 and A/HK/213/03 isolates retain the signature associated with avian receptor binding, but they have a unique amino acid substitution (Ser227Ile) within the receptor binding pocket that was not present even in the closely related A/Gs/HK/739.2/02 (genotype Z+) virus." Recent research reveals that humans have avian type receptors at very low densities and chickens have human type receptors at very low densities. Researchers "found that the mutations at two places in the gene, identified as 182 and 192, allow the virus to bind to both bird and human receptors." See research articles Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic (Centers for Disease Control and Prevention, 2006) (by Gabriele Neumann and Yoshihiro Kawaoka) and Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus (American Association for the Advancement of Science, 2006) (by James Stevens, Ola Blixt, Terrence M. Tumpey, Jeffery K. Taubenberger, James C. Paulson , Ian A. Wilson) for further details. NA codes for neuraminidase which is an antigenic glycoprotein enzyme found on the surface of the influenza viruses . It helps the release of progeny viruses from infected cells. Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase . They were developed based on N2 and N9. "In the N1 form of the protein, a small segment called the 150-loop is inverted, creating a hollow pocket that does not exist in the N2 and N9 proteins. [...] When the researchers looked at how existing drugs interacted with the N1 protein, they found that, in the presence of neuraminidase inhibitors, the loop changed its conformation to one similar to that in the N2 and N9 proteins." HA codes for hemagglutinin , which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to cells . This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins. One genetic factor in distinguishing between human flu viruses and avian flu viruses is that "avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors." A mutation found in Turkey in 2006 "involves a substitution in one sample of an amino acid at position 223 of the haemoagglutinin receptor protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before — in a father and son in Hong Kong in 2003, and in one fatal case in Vietnam last year. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans." [ according to whom? ] Another mutation in the same sample at position 153 has as yet unknown effects. "Amino acid residues at positions 226 and 228 of the receptor binding pocket of HA appear to determine binding affinity to cell surface receptors and to influence the selective binding of the virus to avian (sialic acid -2,3-NeuAcGal) or human (sialic acid -2,6-NeuAcGal) cell surface receptors. The human A/HK/212/03 and A/HK/213/03 isolates retain the signature associated with avian receptor binding, but they have a unique amino acid substitution (Ser227Ile) within the receptor binding pocket that was not present even in the closely related A/Gs/HK/739.2/02 (genotype Z+) virus." Recent research reveals that humans have avian type receptors at very low densities and chickens have human type receptors at very low densities. Researchers "found that the mutations at two places in the gene, identified as 182 and 192, allow the virus to bind to both bird and human receptors." See research articles Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic (Centers for Disease Control and Prevention, 2006) (by Gabriele Neumann and Yoshihiro Kawaoka) and Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus (American Association for the Advancement of Science, 2006) (by James Stevens, Ola Blixt, Terrence M. Tumpey, Jeffery K. Taubenberger, James C. Paulson , Ian A. Wilson) for further details.NA codes for neuraminidase which is an antigenic glycoprotein enzyme found on the surface of the influenza viruses . It helps the release of progeny viruses from infected cells. Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase . They were developed based on N2 and N9. "In the N1 form of the protein, a small segment called the 150-loop is inverted, creating a hollow pocket that does not exist in the N2 and N9 proteins. [...] When the researchers looked at how existing drugs interacted with the N1 protein, they found that, in the presence of neuraminidase inhibitors, the loop changed its conformation to one similar to that in the N2 and N9 proteins." Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses . The segmentation of the influenza genome facilitates genetic recombination by segment reassortment in hosts who are infected with two different influenza viruses at the same time. H5N1 viruses can reassort genes with other strains that co-infect a host organism, such as a pig, bird, or human, and mutate into a form that can pass easily among humans. This is one of many possible paths to a pandemic. The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans. H3N2 (" swine flu ") is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2 , which is now resistant to the standard antiviral drugs amantadine and rimantadine . The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2 . Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source". In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute , Harbin , China and Professor Robert G. Webster of the St. Jude Children's Research Hospital , Memphis, Tennessee , reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity". Results reported by Dr. Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks. Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam , Thailand , and Cambodia and bird isolates from Laos and Malaysia . Clade 2 viruses were first identified in bird isolates from China , Indonesia , Japan , and South Korea before spreading westward to the Middle East , Europe , and Africa . The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Map A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia." See https://web.archive.org/web/20090709040039/http://who.int/csr/disease/avian_influenza/H5CompleteTree.pdf for a Genetic Tree of 1,342 H5N1 viruses based on their HA gene, showing their clade designations.

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Avian influenza

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Influenza A virus subtype H6N2

H6N2 is an avian influenza virus with two forms: one has a low and the other a high pathogenicity . It can cause a serious problem for poultry , and also infects ducks as well. H6N2 subtype is considered to be a non-pathogenic chicken virus, the host still unknown, but could strain from feral animals, and/or aquatic bird reservoirs. H6N2 along with H6N6 are viruses that are found to replicate in mice without preadaptation, and some have acquired the ability to bind to human-like receptors. Genetic markers for H6N2 include 22-amino acid stalk deletion in neuraminidase (NA) protein gene, increased N-glycosylation , and a D144 mutation of the Haemagglutinin (HA) protein gene. Transmission of avian influenza viruses from wild aquatic birds to domestic birds usually cause subclinical infections, and occasionally, respiratory disease and drops in egg production. Some histological features presented in chicken infected with H6N2 are fibrinous yolk peritonitis, salpingitis, oophoritis, nephritis, along with swollen kidneys as well. sneezing and lacrimation prostration anorexia and fever sometimes swelling of the infraorbital sinuses with nasal mucous

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Avian influenza

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Equine influenza

Equine influenza ( horse flu ) is the disease caused by strains of influenza A that are enzootic in horse species. Equine influenza occurs globally, previously caused by two main strains of virus: equine-1 ( H7N7 ) and equine-2 ( H3N8 ). The World Organisation for Animal Health now considers H7N7 strains likely to be extinct since these strains have not been isolated for over 20 years. Predominant international circulating H3N8 strains are Florida sublineage of the American lineage; clade 1 predominates in the Americas and clade 2 in Europe. (Elton and Cullinane, 2013; Paillot, 2014; Slater et al., 2013 ). The disease has a nearly 100% infection rate in an unvaccinated horse population with no prior exposure to the virus. While equine influenza is historically not known to affect humans, impacts of past outbreaks have been devastating due to the economic reliance on horses for communication (postal service), military (cavalry), and general transportation. In modern times the ramifications of equine influenza are most clear in the horse-racing industry.Equine influenza is characterized by a very high rate of transmission among horses, and has a relatively short incubation time of one to three days. Clinical signs of equine influenza include fever (up to 106 °F [41 °C] ), nasal discharge, have a dry, hacking cough, depression, loss of appetite and weakness. Secondary infections may include pneumonia. Horses that are mildly affected will recover within 2 to 3 weeks; however, it may take up to 6 months for recovery for severely affected horses. Horses that become immune may not show signs but will still shed the virus. An 1872 report on equine influenza describes the disease as: "An epizootic specific fever of a very debilitating type, with inflammation of the respiratory mucous membrane, and less frequently of other organs, having an average duration of ten to fifteen days, and not conferring immunity from a second attack in subsequent epizootics."Equine influenza is caused by several strains of the influenza A virus endemic to horses. Viruses that cause equine influenza were first isolated in 1956. The equine-1 virus affects heart muscle, while the equine-2 virus is much more severe and systemic. The virus is spread by infected, coughing horses in addition to contaminated buckets, brushes, tack and other stable equipment. The influenza virus causes symptoms by replicating within respiratory epithelial cells, resulting in destruction of tracheal and bronchial epithelium and cilia. When a horse contracts the equine influenza virus, rest and supportive care is advised so that complications do not occur. Veterinarians recommend at least one week of rest for every day that the fever persists with a minimum of three days' rest. This allows the damaged mucocilliary apparatus to regenerate. Non-steroidal anti-inflammatory drugs are administered if the fever reaches greater than 104 °F (40 °C) . If complications occur, such as the onset of pneumonia, or if the fever last more than 3 to 4 days, antibiotics are often administered. Prevention of equine influenza outbreaks is maintained through vaccines and hygiene procedures. Isolation of horses for two weeks is common practice when they are being moved to a new environment. [ citation needed ] Vaccines ( ATCvet codes: QI05AA01 ( WHO ) inactivated, QI05AD02 ( WHO ) live, plus various combinations) are a major defense against the disease. Vaccination schedules generally require a primary course of vaccines, followed by booster shots . It is recommended that horses be vaccinated against equine influenza annually, and competition horses that travel frequently be given a booster every six months as they are at higher risk of contracting the virus. Foals are initially vaccinated at six months of age with a booster 3 to 6 weeks later and again between 10 and 12 months. Standard schedules may not maintain absolutely foolproof levels of protection, and more frequent administration is advised in high-risk situations. Equine influenza virus (EIV) undergoes continuous antigenic drift, and vaccine protection from immunogenic stimulation is maximised when vaccines strains have greater homogeneity to circulating strains. Subclinically affected vaccinated horses can shed live virus and represent a threat to unvaccinated or inappropriately vaccinated horses. Neutralising immunity leading to an absence of infection is rare. (Paillot, 2014 ) An OIE expert surveillance panel annually assesses circulating strains and makes relevant vaccine recommendations. [ citation needed ] The UK requires horses participating in show events be vaccinated against equine flu, and a vaccination card must be produced. The International Federation for Equestrian Sports requires vaccination every six months. Vaccines ( ATCvet codes: QI05AA01 ( WHO ) inactivated, QI05AD02 ( WHO ) live, plus various combinations) are a major defense against the disease. Vaccination schedules generally require a primary course of vaccines, followed by booster shots . It is recommended that horses be vaccinated against equine influenza annually, and competition horses that travel frequently be given a booster every six months as they are at higher risk of contracting the virus. Foals are initially vaccinated at six months of age with a booster 3 to 6 weeks later and again between 10 and 12 months. Standard schedules may not maintain absolutely foolproof levels of protection, and more frequent administration is advised in high-risk situations. Equine influenza virus (EIV) undergoes continuous antigenic drift, and vaccine protection from immunogenic stimulation is maximised when vaccines strains have greater homogeneity to circulating strains. Subclinically affected vaccinated horses can shed live virus and represent a threat to unvaccinated or inappropriately vaccinated horses. Neutralising immunity leading to an absence of infection is rare. (Paillot, 2014 ) An OIE expert surveillance panel annually assesses circulating strains and makes relevant vaccine recommendations. [ citation needed ] The UK requires horses participating in show events be vaccinated against equine flu, and a vaccination card must be produced. The International Federation for Equestrian Sports requires vaccination every six months. A comprehensive report describing the disease—compiled in response to the 1872 outbreak of the disease in North America—provided a thorough examination of the history of the disease. The report notes putative cases dating as far back as Hippocrates and Livius . Absyrtus , a Greek veterinarian from 330 CE , described a disease in the horse population having the general characters of influenza, which the report mentions as the earliest clear record of equine influenza in the lower animals. [ citation needed ] The report notes the next recorded equine influenza case in 1299, the same year that a catarrhal epidemic affected Europe. Spanish records noted cases in which "The horse carried his head drooping, would eat nothing, ran from the eyes, and there was hurried beating of the flanks. The malady was epidemic, and in that year one thousand horses died." Prevalence of influenza is found in historic records in the centuries of the Middle Ages, but direct implication of horses is not always clear. Neither are recorded instances of record deaths among horses and other animals clear on the exact cause of death. An epizootic outbreak of equine influenza during 1872 in North America became known as "The Great Epizootic of 1872". The outbreak is known as the "most destructive recorded episode of equine influenza in history". In 1870, three fourths of Americans lived in rural areas (towns under 2,500 population, and farms). Horse and mule power was used for moving wagons and carriages, and pulling plows and farm equipment. The census of 1870 counted 7.1 million horses and 1.1 million mules, as well as 39 million humans. With most urban horses and mules incapacitated for a week or two, humans used wheelbarrows and pulled the wagons. About 1% of the animals died, and the rest fully recovered. The first cases of the disease were reported from Ontario, Canada. By October 1, 1872, the first case occurred in Toronto . All the streetcar horses and major livery stables were affected within only three days. By the middle of October, the disease had reached Montreal, Detroit, and New England. On October 25, 1872, The New York Times reported on the extent of the outbreak, claiming that nearly all public stables in the city had been affected, and that the majority of the horses owned in the private sector had essentially been rendered useless to their owners. Only days later, the Times went on to report that 95% of all horses in Rochester, New York, had been affected, while the disease was also making its way quickly through the state of Maine and had already affected all fire horses in the city of Providence, Rhode Island. On October 30, 1872, The New York Times reported that a complete suspension of travel had been noted in the state. The same report also took note of massive freight backups being caused by the lack of transportation ability that was arising as a result of the outbreak. Cities such as Buffalo and New York were left without effective ways to move merchandise through the streets, and even the Erie Canal was left with boats full of goods idling in its waters because they were pulled by horses. By November, many states were reporting cases. The street railway industry ground to a halt in late 1872. Boston was hard hit by a major fire downtown on November 9 as firemen pulled the necessary firefighting equipment by hand. The city commission investigating the fire found that fire crews' response times were delayed by only a matter of minutes. The city then began to buy steam-powered equipment. In New York, 7,000 of the city's approximately 11,000 horses fell ill, and mortality rates ranged between 1.0% and 10%. Many horses were unable to stand in their stalls; those that could stand coughed violently and were too weak to pull any loads or support riders. The vast majority of affected horses that survived were back to full health by the following spring. In December 1872, Mexico sent aid to the United States in the form of live horses. An outbreak involving 1,300 horses in 21 racing stables occurred in Newmarket in Spring 2003. Racing was not cancelled. The equine influenza virus H3N8 caused an influenza outbreak in dogs in the United States. The infection in dogs was first noticed in Greyhound race dogs in January 2004. The exposure and transfer apparently occurred at horse-racing tracks where dog racing had also occurred. Australia had remained free of equine influenza until an outbreak in August 2007 when 10,651 horses were infected over a period of three months. The cost to eradicate the disease was estimated at $1 billion and eventually the virus was successfully contained and Australia has returned to its equine influenza-free status. However, the outbreak had significant effects on the country's horse-racing industry and the Australian economy in general. In February 2019, an outbreak led to horse-racing meetings being cancelled in Britain between February 7 and February 12, after horses from an infected yard in Cheshire had raced the previous day. Following the first three cases at these stables, a further three cases were reported. It became known that there had recently been several outbreaks across Europe, and 7 in the UK since the start of 2019. In the latest incident, initially three vaccinated horses tested positive, resulting in the British Horseracing Authority (BHA) calling off races and putting in place "quarantine and biosecurity measures". The BHA stated "The full extent of potential exposure is unknown". The disease has been spreading across northern Europe, with the Republic of Ireland, France, Belgium and the Netherlands all affected. Within the week following the initial UK infections, four further vaccinated horses tested positive for equine flu in stables in Newmarket, but after six days the BHA declared that (with stricter rules regarding vaccinations) racing would resume. While some in the industry welcomed the resumption of racing, Dr Richard Newton, of the Animal Health Trust warned that British racing is "not out of the woods yet". Eight times as many flu cases were reported among UK horses in the first six weeks of 2019 as in the whole of 2018, and there was particular concern about its appearance in vaccinated horses and thoroughbreds. The outbreak continued at an elevated rate for the first half of the year and a peak in cases was seen at the end of June. From mid-August only isolated sporadic cases were seen. The report notes putative cases dating as far back as Hippocrates and Livius . Absyrtus , a Greek veterinarian from 330 CE , described a disease in the horse population having the general characters of influenza, which the report mentions as the earliest clear record of equine influenza in the lower animals. [ citation needed ] The report notes the next recorded equine influenza case in 1299, the same year that a catarrhal epidemic affected Europe. Spanish records noted cases in which "The horse carried his head drooping, would eat nothing, ran from the eyes, and there was hurried beating of the flanks. The malady was epidemic, and in that year one thousand horses died." Prevalence of influenza is found in historic records in the centuries of the Middle Ages, but direct implication of horses is not always clear. Neither are recorded instances of record deaths among horses and other animals clear on the exact cause of death. An epizootic outbreak of equine influenza during 1872 in North America became known as "The Great Epizootic of 1872". The outbreak is known as the "most destructive recorded episode of equine influenza in history". In 1870, three fourths of Americans lived in rural areas (towns under 2,500 population, and farms). Horse and mule power was used for moving wagons and carriages, and pulling plows and farm equipment. The census of 1870 counted 7.1 million horses and 1.1 million mules, as well as 39 million humans. With most urban horses and mules incapacitated for a week or two, humans used wheelbarrows and pulled the wagons. About 1% of the animals died, and the rest fully recovered. The first cases of the disease were reported from Ontario, Canada. By October 1, 1872, the first case occurred in Toronto . All the streetcar horses and major livery stables were affected within only three days. By the middle of October, the disease had reached Montreal, Detroit, and New England. On October 25, 1872, The New York Times reported on the extent of the outbreak, claiming that nearly all public stables in the city had been affected, and that the majority of the horses owned in the private sector had essentially been rendered useless to their owners. Only days later, the Times went on to report that 95% of all horses in Rochester, New York, had been affected, while the disease was also making its way quickly through the state of Maine and had already affected all fire horses in the city of Providence, Rhode Island. On October 30, 1872, The New York Times reported that a complete suspension of travel had been noted in the state. The same report also took note of massive freight backups being caused by the lack of transportation ability that was arising as a result of the outbreak. Cities such as Buffalo and New York were left without effective ways to move merchandise through the streets, and even the Erie Canal was left with boats full of goods idling in its waters because they were pulled by horses. By November, many states were reporting cases. The street railway industry ground to a halt in late 1872. Boston was hard hit by a major fire downtown on November 9 as firemen pulled the necessary firefighting equipment by hand. The city commission investigating the fire found that fire crews' response times were delayed by only a matter of minutes. The city then began to buy steam-powered equipment. In New York, 7,000 of the city's approximately 11,000 horses fell ill, and mortality rates ranged between 1.0% and 10%. Many horses were unable to stand in their stalls; those that could stand coughed violently and were too weak to pull any loads or support riders. The vast majority of affected horses that survived were back to full health by the following spring. In December 1872, Mexico sent aid to the United States in the form of live horses. An outbreak involving 1,300 horses in 21 racing stables occurred in Newmarket in Spring 2003. Racing was not cancelled. The equine influenza virus H3N8 caused an influenza outbreak in dogs in the United States. The infection in dogs was first noticed in Greyhound race dogs in January 2004. The exposure and transfer apparently occurred at horse-racing tracks where dog racing had also occurred. Australia had remained free of equine influenza until an outbreak in August 2007 when 10,651 horses were infected over a period of three months. The cost to eradicate the disease was estimated at $1 billion and eventually the virus was successfully contained and Australia has returned to its equine influenza-free status. However, the outbreak had significant effects on the country's horse-racing industry and the Australian economy in general. In February 2019, an outbreak led to horse-racing meetings being cancelled in Britain between February 7 and February 12, after horses from an infected yard in Cheshire had raced the previous day. Following the first three cases at these stables, a further three cases were reported. It became known that there had recently been several outbreaks across Europe, and 7 in the UK since the start of 2019. In the latest incident, initially three vaccinated horses tested positive, resulting in the British Horseracing Authority (BHA) calling off races and putting in place "quarantine and biosecurity measures". The BHA stated "The full extent of potential exposure is unknown". The disease has been spreading across northern Europe, with the Republic of Ireland, France, Belgium and the Netherlands all affected. Within the week following the initial UK infections, four further vaccinated horses tested positive for equine flu in stables in Newmarket, but after six days the BHA declared that (with stricter rules regarding vaccinations) racing would resume. While some in the industry welcomed the resumption of racing, Dr Richard Newton, of the Animal Health Trust warned that British racing is "not out of the woods yet". Eight times as many flu cases were reported among UK horses in the first six weeks of 2019 as in the whole of 2018, and there was particular concern about its appearance in vaccinated horses and thoroughbreds. The outbreak continued at an elevated rate for the first half of the year and a peak in cases was seen at the end of June. From mid-August only isolated sporadic cases were seen.

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Avian influenza

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List of epidemics and pandemics

This is a list of the largest known epidemics and pandemics caused by an infectious disease . Widespread non-communicable diseases such as cardiovascular disease and cancer are not included. An epidemic is the rapid spread of disease to a large number of people in a given population within a short period of time; in meningococcal infections , an attack rate in excess of 15 cases per 100,000 people for two consecutive weeks is considered an epidemic. Due to the long time spans, the first plague pandemic (6th century – 8th century) and the second plague pandemic (14th century – early 19th century) are shown by individual outbreaks, such as the Plague of Justinian (first pandemic) and the Black Death (second pandemic). Infectious diseases with high prevalence are listed separately (sometimes in addition to their epidemics), such as malaria , which may have killed 50–60 billion people throughout history, or about half of all humans that have ever lived. Ongoing epidemics and pandemics are in boldface . For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population . Not included in the above table are many waves of deadly diseases brought by Europeans to the Americas and Caribbean. Western Hemisphere populations were ravaged mostly by smallpox , but also typhus , measles , influenza , bubonic plague , cholera , malaria , tuberculosis , mumps , yellow fever , and pertussis . The lack of written records in many places and the destruction of many native societies by disease, war, and colonization make estimates uncertain. Deaths probably numbered in the tens or perhaps over a hundred million, with perhaps 90% of the population dead in the worst-hit areas. Lack of scientific knowledge about microorganisms and lack of surviving medical records for many areas makes attribution of specific numbers to specific diseases uncertain. There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll.Ongoing epidemics and pandemics are in boldface . For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population . Not included in the above table are many waves of deadly diseases brought by Europeans to the Americas and Caribbean. Western Hemisphere populations were ravaged mostly by smallpox , but also typhus , measles , influenza , bubonic plague , cholera , malaria , tuberculosis , mumps , yellow fever , and pertussis . The lack of written records in many places and the destruction of many native societies by disease, war, and colonization make estimates uncertain. Deaths probably numbered in the tens or perhaps over a hundred million, with perhaps 90% of the population dead in the worst-hit areas. Lack of scientific knowledge about microorganisms and lack of surviving medical records for many areas makes attribution of specific numbers to specific diseases uncertain.There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll.Events in boldface are ongoing.

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Live attenuated influenza vaccine

none Live attenuated influenza vaccine ( LAIV ) is a type of influenza vaccine in the form of a nasal spray that is recommended for the prevention of influenza. It was developed by the Syrian-American epidemiologist Hunein Maassab . It is an attenuated live vaccine, unlike other influenza vaccines, which are inactivated vaccines . Live attenuated influenza vaccine is administered intranasally , while inactivated vaccines are administered by intramuscular injection . Live attenuated influenza vaccine is sold under the brand name FluMist Quadrivalent in the United States and the brand name Fluenz Tetra in the European Union. FluMist was first introduced in 2003 by MedImmune . The live attenuated influenza vaccine is used to provide protection against the flu caused by infection with influenza viruses. The use of the live attenuated influenza vaccine is contraindicated , and should therefore not be used, in the following populations:The live attenuated vaccine is based on a flu strain that does not cause disease, that replicates well at relatively cold temperatures (about 25 °C, for incubation purposes), and replicates poorly at body temperature (which minimizes risk to humans). Genes that code for surface proteins (targeted antigens ) are combined with this host using genetic reassortment from strains that are projected to be circulating widely in the coming months. The resulting viruses are then incubated in chicken eggs and chick kidney cells. To make the refrigerated version, the virus is purified in centrifuges through a sucrose gradient, then packaged with sucrose, phosphate , glutamate , arginine , and gelatin made from pigs that has been hydrolyzed with acid. Even though the virus in the live attenuated influenza vaccine is attenuated (low in virulence ), it is still a living virus, and may cause an infection with complications in people with weakened immune systems or other underlying medical conditions. The live attenuated influenza vaccine is recommended only for people 2–49 years of age, and people who have a weakened immune system, pregnant women, and people with certain chronic diseases may not be eligible to receive live attenuated influenza vaccine. In contrast, inactivated virus vaccines contain no living virus, and cannot cause a live infection. Persons receiving the live attenuated influenza vaccine may shed small amounts of the vaccine virus during the first week. People coming in contact with the vaccinated person are not considered to be at risk, unless their immune systems are severely weakened (for example, bone marrow transplant recipients) and possible recombination with other (wild or live vaccine) flu strains. The live attenuated influenza vaccine was developed by the University of Michigan School of Public Health in Ann Arbor, Michigan and later by Aviron, in Mountain View, California , under the sponsorship of the National Institutes of Health (NIH) in the 1990s. MedImmune , Inc. purchased Aviron in 2002, and the US Food and Drug Administration (FDA) approved the live attenuated influenza vaccine in June 2003. The FDA initially approved the live attenuated influenza vaccine only for healthy people aged 5 to 49 because of concerns over possible side effects. The live attenuated influenza vaccine is approved and recommended for healthy children 24 months of age and older. The FDA approved the unfrozen refrigerated version for the same age group (ages 5–49) in August 2006, following completion of phase III clinical trials. The cold-adapted influenza vaccine version of the vaccine is called CAIV-T, and is stable for storage in a refrigerator, rather than requiring freezer storage as did the originally-approved formulation. Approved for the 2007-2008 flu season, the refrigerated formulation can be distributed more economically, so that the price differential with shots (which had hampered sales of the original frozen version of FluMist) is now largely eliminated. FluMist was initially priced higher than the injectable vaccines, but sold only 500,000 of the four million doses it produced its first year on the market, despite a comparative shortage of flu vaccine in fall 2004. The price was sharply lowered the next year, and the company reported distributing 1.6 million doses in 2005. Because of the price drop, despite selling almost three times as many doses in 2005, the company reported $21 million in FluMist sales, compared to $48 million the previous year. MedImmune is one company that manufactures the live attenuated influenza vaccine, which it sells under the brand name FluMist in the United States and the brand name Fluenz Tetra in the European Union. For the 2010–2011 flu season, FluMist was the only live attenuated influenza vaccine approved by the FDA for use in the US. All other FDA-approved lots were inactivated virus vaccines. [ citation needed ] In September 2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved and the seasonal intranasal vaccine was approved by the European Medicines Agency (EMA) for use in the European Union in 2011. The quadrivalent version was approved for use in the European Union in 2013. As of 2007 [ update ] , the only other company holding live attenuated influenza vaccine rights is BioDiem of Australia. BioDiem licensed rights to private production of the vaccine in China to Changchun BCHT Biotechnology, which also holds public rights for production in China sublicensed from the World Health Organization . It was the first and, as of 2007 [ update ] , the only live attenuated vaccine for influenza available outside of Europe. In September 2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved. In 2011, the vaccine was approved by the European Medicines Agency (EMA) for use in the European Union under the brand name Fluenz. AstraZeneca acquired MedImmune and retired the MedImmune name. The live attenuated influenza vaccine is designed to be quickly modifiable to present the surface antigens of seasonal flu. The modifiability could also allow it to be quickly customized as a vaccine against a pandemic influenza if one were to emerge. In light of the global spread of H5N1 , ways of reducing human mortality in the event of an H5N1 pandemic have been investigated. Modifying FluMist to serve as a specific human H5N1 vaccine is among the measures studied. In June 2006, the National Institutes of Health (NIH) began enrolling participants in a Phase I H5N1 study of an intranasal influenza vaccine candidate based on MedImmune 's live, attenuated vaccine technology. In September 2006, the National Institute of Allergy and Infectious Diseases (NIAID) reported that inoculation with a live attenuated influenza vaccine modified to present the surface antigens of certain H5N1 variants provided broad protection against other H5N1 variants in the mouse and ferret models. Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009 study. "Several trials have reported that live attenuated influenza vaccines can boost virus-specific CTLs as well as mucosal and serum antibodies and provide broad cross-protection against heterologous human influenza A viruses." (58, 59) "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses."

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Avian influenza

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Ward J. M. Hagemeijer

Ward J. M. Hagemeijer is a Dutch ecologist and author who publishes about birds and about wetlands. In 1997 Hagemeijer authored The EBCC Atlas of European Breeding Birds . In 2005, while working as an ecologist with Wetlands International ( Wageningen, Netherlands ), Hagemeijer was quoted in the press responding to fears of a widespread outbreak of H5N1 influenza . In September of that year, in response to observed outbreaks in Romania and Turkey, Hagemeijer hypothesized further spread of the disease: "The next step we expect the virus to take is into Africa, because that is on the main migratory route for birds. The first birds are already in east Africa." By December of that year, as events unfolded, he was quoted widely in the Associated Press: "There is more and more evidence building up that wild migratory birds do play some role in spreading the virus, but personally I believe — and others agree — that it's not a major role. If we would assume based on this evidence that wild birds would be a major carrier of the disease we would expect a more dramatic outbreak of the disease all over the world." An alternative hypothesis was that the virus was specialized to spread rapidly in domestic poultry. In Hagemeijer's opinion, a February 2006 outbreak in Nigeria was more likely caused by shipment of domestic poultry than transmission in the wild, because key areas along the flight path such as the Nile delta seemed to have been skipped over. Ward went on to publish five scientific papers in 2007 and 2008 detailing his observations of H5N1 and H5N2 avian influenza in wild bird populations. [ full citation needed ]

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Avian influenza

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1957–1958 influenza pandemic

The 1957–1958 Asian flu pandemic was a global pandemic of influenza A virus subtype H2N2 that originated in Guizhou in Southern China . The number of excess deaths caused by the pandemic is estimated to be 1–4 million around the world (1957–1958 and probably beyond), making it one of the deadliest pandemics in history. A decade later, a reassorted viral strain H3N2 further caused the Hong Kong flu pandemic (1968–1969). The first cases were reported in Guizhou of southern China , in 1956 or in early 1957. Observers within China noted an epidemic beginning in the third week of February in western Guizhou, between its capital Guiyang and the city of Qujing in neighbouring Yunnan province. They were soon reported in Yunnan in late February or early March 1957. By the middle of March, the flu had spread all over China. The People's Republic of China was not a member of the World Health Organization at the time (not until 1981 ), and did not inform other countries about the outbreak. The United States CDC , however, contradicting most records, states that the flu was "first reported in Singapore in February 1957". In late 1957, a second wave of the flu took place in Northern China , especially in rural areas. In the same year, as response to the epidemic, the Chinese government established the Chinese National Influenza Center (CNIC) , which soon published a manual on influenza in 1958. On 17 April 1957, The Times reported that "an influenza epidemic has affected thousands of Hong Kong residents". The same day The New York Times reported that local press estimated at least 250,000 persons were receiving treatment by that time, out of the colony's total population of about 2.5 million. The recent influx of about 700,000 refugees from mainland China had intensified authorities' fears of epidemics and fires due to crowded conditions, and according to a report received by the US Influenza Information Center on 3 May, the disease was said to be occurring mainly among these refugees. By the end of the month (or as early as February ), Singapore also experienced an outbreak of the new flu, which peaked in mid-May with 680 deaths. The only National Influenza Center reporting data to the World Health Organization for the southeast-Asian region in 1957 was located in Singapore, and thus the country was the first to notify the WHO on 4 May about an extensive outbreak of the flu which "appeared to have been introduced from Hong Kong". By the end of May, the outbreak had spread across Mainland Southeast Asia and also involved Indonesia , the Philippines , and Japan . In Taiwan , 100,000 were affected by mid-May. India suffered a million cases by June. In late June, the pandemic reached the United Kingdom . By June 1957, it reached the United States , where it initially caused few infections. Some of the first people affected were US Navy personnel at destroyers docked at Newport Naval Station and new military recruits elsewhere. The first wave peaked in October and affected mainly children who recently returned to school after summer break. The second wave, in January and February 1958, was more pronounced among elderly people and so was more fatal. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. The 1957–1958 pandemic was the first influenza pandemic to occur since the creation of the World Health Organization in 1947. Memories of the 1918 pandemic were still ever-present. In recognition of the worldwide threat of epidemic influenza, the WHO launched its Global Influenza Programme in 1947 with the establishment of the World Influenza Centre at the National Institute for Medical Research in London . This eventually gave rise to the Global Influenza Surveillance Network in 1952 to facilitate global scientific collaboration and fulfil the objectives of the programme. In 1957, China was not a member of the WHO, and thus it was not a part of its influenza surveillance network. Therefore, it took several weeks, if not months, for the news of an outbreak to reach the WHO, when the virus had already spread into Hong Kong and then to Singapore. This fact would be lamented repeatedly after the pandemic, and it was taken as reinforcement of the importance of a "truly worldwide" network of epidemiological surveillance. Following this delay, things then "moved swiftly". After receiving the report out of Singapore in early May, the WHO reported on the developing outbreak for the first time in its Weekly Epidemiological Record published on 10 May. Within three weeks laboratories around the world had concluded that the cause of these epidemics was a new variant of influenza A. This information was first reported in the Weekly Epidemiological Record for 29 May. On 14 June, the WHO declared that attempts at large-scale quarantine were "as costly as they are ineffective", instead recommending only that acute cases be isolated. It reiterated that all reports it had received emphasized the mildness of the disease in most cases, with the very few deaths having occurred mainly in elderly victims suffering from chronic bronchitis. The need for a single, consistent name for the novel virus became clear as it continued to spread and became more commonly discussed. Up to this point, the causative agent had mostly been called "Far East influenza virus" or "Far East strain (influenza virus)" or even "Oriental flu", though "Asian influenza" had been used before. On 11 July, the question was finally taken up at an informal meeting of scientists during the Fourth International Poliomyelitis Congress in Geneva. There it was agreed that "Asian influenza" was a "descriptive and appropriate" name for the "contemporary manifestation of the ancient disease", as the term "Far East" was considered "not exact as to geographical location". On 23 July, the WHO issued a circular letter advising that surplus vaccine be made available to poorer countries at the "lowest economic price". On 16 August, William J. Tepsix, commander of Pennsylvania 's Veterans of Foreign Wars in the United States, sent a letter to United Nations Secretary-General Dag Hammarskjold demanding an investigation into whether the virus had been released by the Soviet Union or China. It is not clear if the UN or the WHO ever responded to Tepsix's letter. However, US Surgeon General Leroy E. Burney would later dismiss this notion on 26 August in response to a similar question raised by the press. On 11 October, the WHO announced that the virus had spread to all populated parts of the world aside from "a few islands or territories having no contact with the outside world". Following the main phase of the pandemic in 1957, the WHO reflected on its performance as part of its review of the first ten years of the organization in 1958. It concluded that "the WHO influenza programme fulfilled the major task allotted to it", which allowed "many parts of the world to organize health services to meet the threat and for some countries to attempt to protect priority groups by vaccination". However, it acknowledged that had its influenza surveillance network been "truly worldwide", as it would repeatedly lament it was not, then preparations could have begun two months earlier. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. The number of deaths peaked the week ending 17 October, with 600 reported in England and Wales . The vaccine was available in the same month in the United Kingdom. Although it was initially available only in limited quantities, its rapid deployment helped contain the pandemic. Hilleman's vaccine is believed to have saved hundreds of thousands of lives. Some predicted that the U.S. death toll would have reached 1 million without the vaccine that Hilleman called for. H2N2 influenza virus continued to be transmitted until 1968, when it transformed via antigenic shift into influenza A virus subtype H3N2 , the cause of the 1968 influenza pandemic . The first cases were reported in Guizhou of southern China , in 1956 or in early 1957. Observers within China noted an epidemic beginning in the third week of February in western Guizhou, between its capital Guiyang and the city of Qujing in neighbouring Yunnan province. They were soon reported in Yunnan in late February or early March 1957. By the middle of March, the flu had spread all over China. The People's Republic of China was not a member of the World Health Organization at the time (not until 1981 ), and did not inform other countries about the outbreak. The United States CDC , however, contradicting most records, states that the flu was "first reported in Singapore in February 1957". In late 1957, a second wave of the flu took place in Northern China , especially in rural areas. In the same year, as response to the epidemic, the Chinese government established the Chinese National Influenza Center (CNIC) , which soon published a manual on influenza in 1958. On 17 April 1957, The Times reported that "an influenza epidemic has affected thousands of Hong Kong residents". The same day The New York Times reported that local press estimated at least 250,000 persons were receiving treatment by that time, out of the colony's total population of about 2.5 million. The recent influx of about 700,000 refugees from mainland China had intensified authorities' fears of epidemics and fires due to crowded conditions, and according to a report received by the US Influenza Information Center on 3 May, the disease was said to be occurring mainly among these refugees. By the end of the month (or as early as February ), Singapore also experienced an outbreak of the new flu, which peaked in mid-May with 680 deaths. The only National Influenza Center reporting data to the World Health Organization for the southeast-Asian region in 1957 was located in Singapore, and thus the country was the first to notify the WHO on 4 May about an extensive outbreak of the flu which "appeared to have been introduced from Hong Kong". By the end of May, the outbreak had spread across Mainland Southeast Asia and also involved Indonesia , the Philippines , and Japan . In Taiwan , 100,000 were affected by mid-May. India suffered a million cases by June. In late June, the pandemic reached the United Kingdom . By June 1957, it reached the United States , where it initially caused few infections. Some of the first people affected were US Navy personnel at destroyers docked at Newport Naval Station and new military recruits elsewhere. The first wave peaked in October and affected mainly children who recently returned to school after summer break. The second wave, in January and February 1958, was more pronounced among elderly people and so was more fatal. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ]The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. The 1957–1958 pandemic was the first influenza pandemic to occur since the creation of the World Health Organization in 1947. Memories of the 1918 pandemic were still ever-present. In recognition of the worldwide threat of epidemic influenza, the WHO launched its Global Influenza Programme in 1947 with the establishment of the World Influenza Centre at the National Institute for Medical Research in London . This eventually gave rise to the Global Influenza Surveillance Network in 1952 to facilitate global scientific collaboration and fulfil the objectives of the programme. In 1957, China was not a member of the WHO, and thus it was not a part of its influenza surveillance network. Therefore, it took several weeks, if not months, for the news of an outbreak to reach the WHO, when the virus had already spread into Hong Kong and then to Singapore. This fact would be lamented repeatedly after the pandemic, and it was taken as reinforcement of the importance of a "truly worldwide" network of epidemiological surveillance. Following this delay, things then "moved swiftly". After receiving the report out of Singapore in early May, the WHO reported on the developing outbreak for the first time in its Weekly Epidemiological Record published on 10 May. Within three weeks laboratories around the world had concluded that the cause of these epidemics was a new variant of influenza A. This information was first reported in the Weekly Epidemiological Record for 29 May. On 14 June, the WHO declared that attempts at large-scale quarantine were "as costly as they are ineffective", instead recommending only that acute cases be isolated. It reiterated that all reports it had received emphasized the mildness of the disease in most cases, with the very few deaths having occurred mainly in elderly victims suffering from chronic bronchitis. The need for a single, consistent name for the novel virus became clear as it continued to spread and became more commonly discussed. Up to this point, the causative agent had mostly been called "Far East influenza virus" or "Far East strain (influenza virus)" or even "Oriental flu", though "Asian influenza" had been used before. On 11 July, the question was finally taken up at an informal meeting of scientists during the Fourth International Poliomyelitis Congress in Geneva. There it was agreed that "Asian influenza" was a "descriptive and appropriate" name for the "contemporary manifestation of the ancient disease", as the term "Far East" was considered "not exact as to geographical location". On 23 July, the WHO issued a circular letter advising that surplus vaccine be made available to poorer countries at the "lowest economic price". On 16 August, William J. Tepsix, commander of Pennsylvania 's Veterans of Foreign Wars in the United States, sent a letter to United Nations Secretary-General Dag Hammarskjold demanding an investigation into whether the virus had been released by the Soviet Union or China. It is not clear if the UN or the WHO ever responded to Tepsix's letter. However, US Surgeon General Leroy E. Burney would later dismiss this notion on 26 August in response to a similar question raised by the press. On 11 October, the WHO announced that the virus had spread to all populated parts of the world aside from "a few islands or territories having no contact with the outside world". Following the main phase of the pandemic in 1957, the WHO reflected on its performance as part of its review of the first ten years of the organization in 1958. It concluded that "the WHO influenza programme fulfilled the major task allotted to it", which allowed "many parts of the world to organize health services to meet the threat and for some countries to attempt to protect priority groups by vaccination". However, it acknowledged that had its influenza surveillance network been "truly worldwide", as it would repeatedly lament it was not, then preparations could have begun two months earlier. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. The number of deaths peaked the week ending 17 October, with 600 reported in England and Wales . The vaccine was available in the same month in the United Kingdom. Although it was initially available only in limited quantities, its rapid deployment helped contain the pandemic. Hilleman's vaccine is believed to have saved hundreds of thousands of lives. Some predicted that the U.S. death toll would have reached 1 million without the vaccine that Hilleman called for. H2N2 influenza virus continued to be transmitted until 1968, when it transformed via antigenic shift into influenza A virus subtype H3N2 , the cause of the 1968 influenza pandemic . The strain of virus that caused the Asian flu pandemic, influenza A virus subtype H2N2 , was a recombination of avian influenza (probably from geese) and human influenza viruses. As it was a novel strain of the virus, the population had minimal immunity . The reproduction number for the virus was around 1.8 and approximately two-thirds of infected individuals were estimated to have experienced clinical symptoms. It could cause pneumonia by itself without the presence of secondary bacterial infection . It caused many infections in children, spread in schools, and led to many school closures. However, the virus was rarely fatal in children and was most deadly in pregnant women, the elderly, and those with pre-existing heart and lung disease. In October 1957, Leroy Edgar Burney told The New York Times that the pandemic is mild and the case fatality rate (CFR) is below "two-thirds of 1 per cent", or less than 0.67%. After the pandemic, information from 29 general practices in the UK estimated 2.3 deaths per 1,000 medically attended cases. A survey based on randomly selected families in Kolkata, India, revealed that there were 1,055 deaths in 1,496,000 cases. On the symposium of Asian influenza in 1958, a range of CFR from 0.01% to 0.33% was provided, most frequently in between 0.02% and 0.05%. More recently, the World Health Organization estimated the CFR of Asian flu to be lower than 0.2%. In the US pandemic preparedness plan, the CDC estimated the CFR of 1957 pandemic to be 0.1%. The estimated CFR from first wave morbidity and excess mortality in Norway is in between 0.04% and 0.11%. Other scholars estimated the CFR near 0.1%. The flu may have infected as many as or more people than the 1918 Spanish flu pandemic , but the vaccine, improved health care, and the invention of antibiotics to manage opportunistic bacterial infections contributed to a lower mortality rate. Most estimates of excessive deaths due to the pandemic range from 1-4 million, some of which include years beyond 1958. In particular, the attempt by the National Institutes of Health in 2016 attributed global mortality 1.1 million (0.7 to 1.5 million) excess deaths to the pandemic, including the year 1959. This estimate of global burden has recently been adopted by the World Health Organization and US CDC . The study also estimated the excess deaths in the first year of the pandemic, in 1957, to be 0.6 million (0.4 to 0.8 million). The Dow Jones Industrial Average lost 15% of its value in the second half of 1957, and the U.S. experienced a recession . In the United Kingdom , the government paid out £10,000,000 in sickness benefit , and some factories and mines had to close. Many schools had to close in Ireland , including seventeen in Dublin .

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Hemagglutinin_(influenza)/html

Hemagglutinin (influenza)

Influenza hemagglutinin ( HA ) or haemagglutinin [p] ( British English ) is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity. Hemagglutinin is a Class I Fusion Protein , having multifunctional activity as both an attachment factor and membrane fusion protein . Therefore, HA is responsible for binding Influenza virus to sialic acid on the surface of target cells, such as cells in the upper respiratory tract or erythrocytes , causing as a result the internalization of the virus. Secondarily, HA is responsible for the fusion of the viral envelope with the late endosomal membrane once exposed to low pH (5.0-5.5). The name "hemagglutinin" comes from the protein 's ability to cause red blood cells (erythrocytes) to clump together (" agglutinate ") in vitro . Hemagglutinin (HA) in influenza A has at least 18 different subtypes. These subtypes are named H1 through H18. H16 was discovered in 2004 on influenza A viruses isolated from black-headed gulls from Sweden and Norway . H17 was discovered in 2012 in fruit bats. Most recently, H18 was discovered in a Peruvian bat in 2013. The first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses. By phylogenic similarity, the HA proteins are divided into 2 groups, with H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17, and H18 belonging to group 1 and the rest in group 2. The serotype of influenza A virus is determined by the Hemagglutinin (HA) and Neuraminidase (NA) proteins present on its surface. Neuraminidase (NA) has 11 known subtypes, hence influenza virus is named as H1N1, H5N2 etc., depending on the combinations of HA and NA. [ citation needed ] A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. It has been reported that single amino acid changes in this avian virus strain's type H5 hemagglutinin have been found in human patients that "can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses". This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by proteolysis . HA is a homotrimeric integral membrane glycoprotein . It is shaped like a cylinder , and is approximately 13.5 nanometres long. HA trimer is made of three identical monomers . Each monomer is made of an intact HA0 single polypeptide chain with HA1 and HA2 regions that are linked by 2 disulfide bridges . Each HA2 region adopts alpha helical coiled coil structure and sits on top of the HA1 region, which is a small globular domain that consists of a mix of α/β structures. The HA trimer is synthesized as inactive precursor protein HA0 to prevent any premature and unwanted fusion activity and must be cleaved by host proteases in order to be infectious. At neutral pH, the 23 residues near the N-terminus of HA2, also known as the fusion peptide that is eventually responsible for fusion between viral and host membrane, is hidden in a hydrophobic pocket between the HA2 trimeric interface. The C-terminus of HA2, also known as the transmembrane domain , spans the viral membrane and anchors protein to the membrane. HA plays two key functions in viral entry. Firstly, it allows the recognition of target vertebrate cells, accomplished through the binding to these cells' sialic acid -containing receptors . Secondly, once bound it facilitates the entry of the viral genome into the target cells by causing the fusion of host endosomal membrane with the viral membrane. Specifically, the HA1 domain of the protein binds to the monosaccharide sialic acid which is present on the surface of its target cells, allowing attachment of viral particle to the host cell surface. HA17 and HA18 have been described to bind MHC class II molecules as a receptor for entry rather than sialic acid. The host cell membrane then engulfs the virus, a process known as endocytosis , and pinches off to form a new membrane-bound compartment within the cell called an endosome . The cell then attempts to begin digesting the contents of the endosome by acidifying its interior and transforming it into a lysosome . Once the pH within the endosome drops to about 5.0 to 6.0, a series of conformational rearrangement occurs to the protein. First, fusion peptide is released from the hydrophobic pocket and HA1 is dissociated from HA2 domain. HA2 domain then undergoes extensive conformation change that eventually bring the two membranes into close contact. [ citation needed ] This so-called " fusion peptide " that was released as pH is lowered, acts like a molecular grappling hook by inserting itself into the endosomal membrane and locking on. Then, HA2 refolds into a new structure (which is more stable at the lower pH), it "retracts the grappling hook" and pulls the endosomal membrane right up next to the virus particle's own membrane, causing the two to fuse together. Once this has happened, the contents of the virus such as viral RNA are released in the host cell's cytoplasm and then transported to the host cell nucleus for replication. Since hemagglutinin is the major surface protein of the influenza A virus and is essential to the entry process, it is the primary target of neutralizing antibodies . [ citation needed ] These antibodies against flu have been found to act by two different mechanisms, mirroring the dual functions of hemagglutinin: Some antibodies against hemagglutinin act by inhibiting attachment. This is because these antibodies bind near the top of the hemagglutinin "head" (blue region in figure above) and physically block the interaction with sialic acid receptors on target cells. This group of antibodies acts by preventing membrane fusion (only in vitro ; the efficacy of these antibodies in vivo is believed to be a result of antibody-dependent cell-mediated cytotoxicity and the complement system ). The stem or stalk region of HA (HA2), is highly conserved across different strains of influenza viruses. The conservation makes it an attractive target for broadly neutralizing antibodies that target all flu subtypes, and for developing universal vaccines that let humans produce these antibodies naturally. Its structural changes from prefusion to postfusion conformation drives fusion between viral membrane and host membrane. Therefore, antibodies targeting this region can block key structural changes that eventually drive the membrane fusion process, and therefore are able to achieve antiviral activity against several influenza virus subtypes. At least one fusion-inhibiting antibody was found to bind closer to the top of hemagglutinin, and is thought to work by cross-linking the heads together, the opening of which is thought to be the first step in the membrane fusion process. Examples are human antibodies F10, FI6, CR6261 . They recognize sites in the stem/stalk region (orange region in figure at right), far away from the receptor binding site. In 2015 researchers designed an immunogen mimicking the HA stem, specifically the area where the antibody ties to the virus of the antibody CR9114. Rodent and nonhuman primate models given the immunogen produced antibodies that could bind with HAs in many influenza subtypes, including H5N1 . When the HA head is present, the immune system does not generally make bNAbs (broadly neutralizing antibodies). Instead, it makes the head antibodies that only recognize a few subtypes. Since the head is responsible for holding the three HA units together, a stem-only HA needs its own way to hold itself together. One team designed self-assembling HA-stem nanoparticles, using a protein called ferritin to hold the HA together. Another replaced and added amino acids to stabilize a mini-HA lacking a proper head. [ citation needed ] A 2016 vaccine trial in humans found many broadly neutralizing antibodies targeting the stem produced by the immune system. Three classes of highly similar antibodies were recovered from multiple human volunteers, suggesting that a universal vaccine that produces reproducible antibodies is indeed possible. There are also other hemagglutinin-targeted influenza virus inhibitors that are not antibodies: Arbidol Small Molecules Natural compounds Proteins and peptidesSome antibodies against hemagglutinin act by inhibiting attachment. This is because these antibodies bind near the top of the hemagglutinin "head" (blue region in figure above) and physically block the interaction with sialic acid receptors on target cells. This group of antibodies acts by preventing membrane fusion (only in vitro ; the efficacy of these antibodies in vivo is believed to be a result of antibody-dependent cell-mediated cytotoxicity and the complement system ). The stem or stalk region of HA (HA2), is highly conserved across different strains of influenza viruses. The conservation makes it an attractive target for broadly neutralizing antibodies that target all flu subtypes, and for developing universal vaccines that let humans produce these antibodies naturally. Its structural changes from prefusion to postfusion conformation drives fusion between viral membrane and host membrane. Therefore, antibodies targeting this region can block key structural changes that eventually drive the membrane fusion process, and therefore are able to achieve antiviral activity against several influenza virus subtypes. At least one fusion-inhibiting antibody was found to bind closer to the top of hemagglutinin, and is thought to work by cross-linking the heads together, the opening of which is thought to be the first step in the membrane fusion process. Examples are human antibodies F10, FI6, CR6261 . They recognize sites in the stem/stalk region (orange region in figure at right), far away from the receptor binding site. In 2015 researchers designed an immunogen mimicking the HA stem, specifically the area where the antibody ties to the virus of the antibody CR9114. Rodent and nonhuman primate models given the immunogen produced antibodies that could bind with HAs in many influenza subtypes, including H5N1 . When the HA head is present, the immune system does not generally make bNAbs (broadly neutralizing antibodies). Instead, it makes the head antibodies that only recognize a few subtypes. Since the head is responsible for holding the three HA units together, a stem-only HA needs its own way to hold itself together. One team designed self-assembling HA-stem nanoparticles, using a protein called ferritin to hold the HA together. Another replaced and added amino acids to stabilize a mini-HA lacking a proper head. [ citation needed ] A 2016 vaccine trial in humans found many broadly neutralizing antibodies targeting the stem produced by the immune system. Three classes of highly similar antibodies were recovered from multiple human volunteers, suggesting that a universal vaccine that produces reproducible antibodies is indeed possible. There are also other hemagglutinin-targeted influenza virus inhibitors that are not antibodies: Arbidol Small Molecules Natural compounds Proteins and peptides

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/GISAID/html

GISAID

GISAID ( / ˈ ɡ ɪ s eɪ d / ), the Global Initiative on Sharing All Influenza Data , previously the Global Initiative on Sharing Avian Influenza Data , is a global science initiative established in 2008 to provide access to genomic data of influenza viruses. The database was expanded to include the coronavirus responsible for the COVID-19 pandemic , as well as other pathogens. The database has been described as "the world's largest repository of COVID-19 sequences". GISAID facilitates genomic epidemiology and real-time surveillance to monitor the emergence of new COVID-19 viral strains across the planet. Since its establishment as an alternative to sharing avian influenza data via conventional public-domain archives, GISAID has facilitated the exchange of outbreak genome data during the H1N1 pandemic in 2009, the H7N9 epidemic in 2013, the COVID-19 pandemic and the 2022–2023 mpox outbreak . Since 1952, influenza strains had been collected by National Influenza Centers (NICs) and distributed through the WHO's Global Influenza Surveillance and Response System (GISRS). Countries provided samples to the WHO but the data was then shared with them for free with pharmaceutical companies who could patent vaccines produced from the samples. Beginning in January 2006, Italian researcher Ilaria Capua refused to upload her data to a closed database and called for genomic data on H5N1 avian influenza to be in the public domain. At a conference of the OIE/FAO Network of Expertise on Animal Influenza , Capua persuaded participants to agree to each sequence and release data on 20 strains of influenza. Some scientists had concerns about sharing their data in case others published scientific papers using the data before them, but Capua dismissed this telling Science "What is more important? Another paper for Ilaria Capua's team or addressing a major health threat? Let's get our priorities straight." Peter Bogner , a German in his 40s based in the USA and who previously had no experience in public health, read an article about Capua's call and helped to found and fund GISAID. Bogner met Nancy Cox , who was then leading the US Centers for Disease Control 's influenza division at a conference, and Cox went on to chair GISAID's Scientific Advisory Council. The acronym GISAID was coined in a correspondence letter published in the journal Nature in August 2006, putting forward an initial aspiration of creating a consortium for a new Global Initiative on Sharing Avian Influenza Data (later, "All" would replace "Avian"), whereby its members would release data in publicly available databases up to six months after analysis and validation. Initially the organisation collaborated with the Australian non-profit organization Cambia and the Creative Commons project Science Commons . Although no essential ground rules for sharing were established, the correspondence letter was signed by over 70 leading scientists, including seven Nobel laureates , because access to the most current genetic data for the highly pathogenic H5N1 zoonotic virus was often restricted, in part due to the hesitancy of World Health Organization member states to share their virus genomes and put ownership rights at risk. Towards the end of 2006, Indonesia announced it would not share samples of avian flu with the WHO which led to a global health crisis due to an ongoing epidemic. By October 2006, Indonesia had agreed to share their data with GISAID, which their health minister considered to have a "fair and transparent" mechanism for sharing data. It was one of the first countries to do so. In February 2007, GISAID and the Swiss Institute of Bioinformatics (SIB) announced a cooperation agreement, with the SIB building and administering the EpiFlu database on behalf of GISAID. Ultimately, GISAID was launched in May 2008 in Geneva on the occasion of the 61st World Health Assembly, as a registration-based database rather than a consortium. In 2009 SIB disconnected the database from the GISAID portal over a contract dispute, resulting in litigation. In April 2010 the Federal Republic of Germany announced during the 7th International Ministerial Conference on Avian and Pandemic Influenza in Hanoi , Vietnam , that GISAID had entered into a cooperation agreement with the German government, making Germany the long-term host of the GISAID platform. Under the agreement, Germany's Federal Ministry of Food, Agriculture and Consumer Protection was to ensure the sustainability of the initiative by providing technical hosting facilities, and the Federal Institute for Animal Health , the Friedrich Loeffler Institute , was to ensure the plausibility and curation of scientific data in GISAID. By 2021, the ministry was no longer involved with either database hosting nor curation. In 2013 GISAID dissolved a nonprofit organisation based in Washington DC and the organisation began to be operated by a German association called Freunde von GISAID (Friends of GISAID). Some of the earliest SARS-CoV-2 genetic sequences were released by the Chinese Center for Disease Control and Prevention and shared through GISAID in mid January 2020. Since 2020, millions of SARS-CoV-2 genome sequences have been uploaded to the GISAID database. In 2022, GISAID added Mpox virus and Respiratory syncytial virus (RSV) to the list of pathogens supported by its database. Indonesia's Ministry of Health announced in November 2023 the establishment of GISAID Academy in Bali , to focus on bioinformatics education, advance pathogen genomic surveillance, and increased regional response capacity. The GISAID model of incentivizing and recognizing those who deposit data has been recommended as a model for future initiatives; Because of this work, the entity has been described as "a critical shield for humankind". GISAID maintains what has been described as "the world's largest repository of COVID-19 sequences", and "by far the world's largest database of SARS-CoV-2 sequences". By mid-April 2021, GISAID's SARS-CoV-2 database reached over 1,200,000 submissions, a testament to the hard work of researchers in over 170 different countries. Only three months later, the number of uploaded SARS-CoV-2 sequences had doubled again, to over 2.4 million. By late 2021, the database contained over 5 million genome sequences; as of December 2021, over 6 million sequences had been submitted; by April 2022, there were 10 million sequences accumulated; and in January 2023 the number had reached 14.4 million. In January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID. Throughout the first year of the COVID-19 pandemic, most of the SARS-CoV-2 whole-genome sequences that were generated and shared globally were submitted through GISAID. When the SARS-CoV-2 Omicron variant was detected in South Africa, by quickly uploading the sequence to GISAID, the National Institute for Communicable Diseases there was able to learn that Botswana and Hong Kong had also reported cases possessing the same gene sequence. In March 2023, GISAID temporarily suspended database access for some scientists, removing raw data relevant to investigations of the origins of SARS-CoV-2 . GISAID stated that they do not delete records from their database, but data may become temporarily invisible during updates or corrections. Availability of the data was restored, with an additional restriction that any analysis based thereon would not be shared with the public. Since 1952, influenza strains had been collected by National Influenza Centers (NICs) and distributed through the WHO's Global Influenza Surveillance and Response System (GISRS). Countries provided samples to the WHO but the data was then shared with them for free with pharmaceutical companies who could patent vaccines produced from the samples. Beginning in January 2006, Italian researcher Ilaria Capua refused to upload her data to a closed database and called for genomic data on H5N1 avian influenza to be in the public domain. At a conference of the OIE/FAO Network of Expertise on Animal Influenza , Capua persuaded participants to agree to each sequence and release data on 20 strains of influenza. Some scientists had concerns about sharing their data in case others published scientific papers using the data before them, but Capua dismissed this telling Science "What is more important? Another paper for Ilaria Capua's team or addressing a major health threat? Let's get our priorities straight." Peter Bogner , a German in his 40s based in the USA and who previously had no experience in public health, read an article about Capua's call and helped to found and fund GISAID. Bogner met Nancy Cox , who was then leading the US Centers for Disease Control 's influenza division at a conference, and Cox went on to chair GISAID's Scientific Advisory Council. The acronym GISAID was coined in a correspondence letter published in the journal Nature in August 2006, putting forward an initial aspiration of creating a consortium for a new Global Initiative on Sharing Avian Influenza Data (later, "All" would replace "Avian"), whereby its members would release data in publicly available databases up to six months after analysis and validation. Initially the organisation collaborated with the Australian non-profit organization Cambia and the Creative Commons project Science Commons . Although no essential ground rules for sharing were established, the correspondence letter was signed by over 70 leading scientists, including seven Nobel laureates , because access to the most current genetic data for the highly pathogenic H5N1 zoonotic virus was often restricted, in part due to the hesitancy of World Health Organization member states to share their virus genomes and put ownership rights at risk. Towards the end of 2006, Indonesia announced it would not share samples of avian flu with the WHO which led to a global health crisis due to an ongoing epidemic. By October 2006, Indonesia had agreed to share their data with GISAID, which their health minister considered to have a "fair and transparent" mechanism for sharing data. It was one of the first countries to do so. In February 2007, GISAID and the Swiss Institute of Bioinformatics (SIB) announced a cooperation agreement, with the SIB building and administering the EpiFlu database on behalf of GISAID. Ultimately, GISAID was launched in May 2008 in Geneva on the occasion of the 61st World Health Assembly, as a registration-based database rather than a consortium. In 2009 SIB disconnected the database from the GISAID portal over a contract dispute, resulting in litigation. In April 2010 the Federal Republic of Germany announced during the 7th International Ministerial Conference on Avian and Pandemic Influenza in Hanoi , Vietnam , that GISAID had entered into a cooperation agreement with the German government, making Germany the long-term host of the GISAID platform. Under the agreement, Germany's Federal Ministry of Food, Agriculture and Consumer Protection was to ensure the sustainability of the initiative by providing technical hosting facilities, and the Federal Institute for Animal Health , the Friedrich Loeffler Institute , was to ensure the plausibility and curation of scientific data in GISAID. By 2021, the ministry was no longer involved with either database hosting nor curation. In 2013 GISAID dissolved a nonprofit organisation based in Washington DC and the organisation began to be operated by a German association called Freunde von GISAID (Friends of GISAID). Some of the earliest SARS-CoV-2 genetic sequences were released by the Chinese Center for Disease Control and Prevention and shared through GISAID in mid January 2020. Since 2020, millions of SARS-CoV-2 genome sequences have been uploaded to the GISAID database. In 2022, GISAID added Mpox virus and Respiratory syncytial virus (RSV) to the list of pathogens supported by its database. Indonesia's Ministry of Health announced in November 2023 the establishment of GISAID Academy in Bali , to focus on bioinformatics education, advance pathogen genomic surveillance, and increased regional response capacity. The GISAID model of incentivizing and recognizing those who deposit data has been recommended as a model for future initiatives; Because of this work, the entity has been described as "a critical shield for humankind". GISAID maintains what has been described as "the world's largest repository of COVID-19 sequences", and "by far the world's largest database of SARS-CoV-2 sequences". By mid-April 2021, GISAID's SARS-CoV-2 database reached over 1,200,000 submissions, a testament to the hard work of researchers in over 170 different countries. Only three months later, the number of uploaded SARS-CoV-2 sequences had doubled again, to over 2.4 million. By late 2021, the database contained over 5 million genome sequences; as of December 2021, over 6 million sequences had been submitted; by April 2022, there were 10 million sequences accumulated; and in January 2023 the number had reached 14.4 million. In January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID. Throughout the first year of the COVID-19 pandemic, most of the SARS-CoV-2 whole-genome sequences that were generated and shared globally were submitted through GISAID. When the SARS-CoV-2 Omicron variant was detected in South Africa, by quickly uploading the sequence to GISAID, the National Institute for Communicable Diseases there was able to learn that Botswana and Hong Kong had also reported cases possessing the same gene sequence. In March 2023, GISAID temporarily suspended database access for some scientists, removing raw data relevant to investigations of the origins of SARS-CoV-2 . GISAID stated that they do not delete records from their database, but data may become temporarily invisible during updates or corrections. Availability of the data was restored, with an additional restriction that any analysis based thereon would not be shared with the public. The board of Friends of GISAID consists of Peter Bogner and two German lawyers who are not involved in the day-to-day operations of the organisation. Scientific advice to the organization is provided by its Scientific Advisory Council, including directors of leading public health laboratories , such as WHO Collaborating Centres for Influenza. In 2023, GISAID's lack of transparency was criticized by some GISAID funders, including the European Commission and the Rockefeller Foundation , with long-term funding being denied from International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) . In June 2023, it was reported in Vanity Fair that Bogner had said that "GISAID will soon launch an independent compliance board 'responsible for addressing a wide range of governance matters'". The Telegraph similarly reported that GISAID's in-house counsel was developing new governance processes intended to be transparent and allow for the resolution of scientific disputes without the involvement of Bogner. The creation of the GISAID database was motivated in part by concerns raised by researchers from developing countries , with Scientific American noting in 2009 that that "a previous data-sharing system run by WHO forced them to give up intellectual property rights to their virus samples when they sent them to WHO. The virus samples would then be used by private pharmaceutical companies to make vaccines that are awarded patents and sold at a profit at prices many poor nations cannot afford". In a 2022 piece in The Lancet , it was further noted that scientists in North America and Europe sought unrestricted access, with "scientists from Africa requiring sufficient protections for those who generate and share data as per the GISAID terms and conditions". Unlike public-domain databases such as GenBank and EMBL , users of GISAID must have their identity confirmed and agree to a Database Access Agreement that governs the way GISAID data can be used. These Terms of Use are "weighted in favour of the data provider and gives them enduring control over the genetic data they upload". They prevent users from sharing any data with other users who have not agreed to them, and require that users of the data must credit the data generators in published work, and also make a reasonable attempt to collaborate with data generators and involve them in research and analysis that uses their data. A difficulty that GISAID's Data Access Agreement attempts to address is that many researchers fear sharing of influenza sequence data could facilitate its misappropriation through intellectual property claims by the vaccine industry and others, hindering access to vaccines and other items in developing countries, either through high costs or by preventing technology transfer . While most public interest experts agree with GISAID that influenza sequence data should be made public, and this is the subject of agreement by many researchers, some provide the information only after filing patent claims while others have said that access to it should be only on the condition that no patents or other intellectual property claims are filed, as was controversial with the Human Genome Project . GISAID's Data Access Agreement addresses this directly to promote sharing data. GISAID's procedures additionally suggest that those who access the EpiFlu database consult the countries of origin of genetic sequences and the researchers who discovered the sequences. As a result, the GISAID license has been important in rapid pandemic preparedness. However, these restrictions evidence common criticisms to an open data model . GISAID describes itself as "open access", which is naturally replicated by the media and in journal publications. This description indeed aligns with the original announcement of the consortium, which also mentioned depositing the data to the databases participating in the INSDC . As of March 2023, this is not the case, as "GISAID does not offer a mechanism to release data to any other database". A few academic papers have compared GISAID's licensing model to unrestricted, open databases , highlighting the differences while other researchers have signed an open letter calling for the use of any of the INSDC's unrestricted databases. In 2017, GISAID's editorial board stated that " re3data.org and DataCite , the world's leading provider of digital object identifiers (DOI) for research data, affirmed the designation of access to GISAID's database and data as Open Access". However, after several researchers had their accounts suspended in March 2023 as reported by the journal Science and other news outlets, its open access status was revoked by the Registry of Research Data Repositories (re3data) , which now classifies it as a "restricted access repository". In 2020 the World Health Organization chief scientist Soumya Swaminathan called the initiative "a game changer", while the co-director of the European Bioinformatics Institute (EBI) Rolf Apweiler has argued that because it does not allow sequences to be reshared publicly, it hampers efforts to understand the coronavirus and the rapid rise of new variants. GISAID's restrictions on access have led to conflict with "labs and institutions whose priorities are academic rather than driven by the immediate priorities of public health protection". In January 2021, GISAID's restricted access led a group of scientists to write an open letter asking for SARS-CoV-2 sequences to be deposited in open databases, which was replicated in the journals Nature and Science . Furthermore, the article from Science points out that the lack of transparency in access to the database also prevents many scientists from even criticising the platform. A paper from 2017 describing the success of GISAID mentions that revoking researchers' credentials was rare, but it did happen. The same publication described a "perceived merit in GISAID's formula for balancing the need for control and openness". In April 2023, Science and The Economist reported these issues continue as well as the lack of transparency of its governance. An investigation by The Telegraph into claims made by Science noted the incentives of various potential competitors in the field, for whom GISAID is an obstacle to consolidation of control over the field, and also noted that GISAID's position inevitably places it at the center of disputes between groups of scientists, which will tend to result in the losing side blaming GISAID for that outcome.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/2017_Central_Luzon_H5N6_outbreak/html

2017 Central Luzon H5N6 outbreak

From April to September 2017 in the Philippines, an outbreak of H5N6 avian influenza or bird flu affected poultry in at least three towns in Central Luzon ; San Luis in Pampanga and Jaen and San Isidro in Nueva Ecija . The occurrence is the first avian flu outbreak recorded in the Philippines. While the occurrence of the disease was reported as early as April 2017, it was only on August 11, 2017, that the avian flu was confirmed. The outbreak was officially declared over in September 2017.Occurrence of avian influenza in Pampanga was first reported by farms in the last week of April 2017. The first farm to be affected by the disease was reportedly a quail farm. The Department of Agriculture (DA) confirmed the avian influenza outbreak on August 11, 2017, and a state of calamity was declared by the provincial government of Pampanga on the same day. By that time a total of 116,000 birds in farms has been identified to have the virus with 37,000 birds already dead due to the disease. On August 18, 2017, Agriculture Secretary Manny Piñol confirmed occurrence of bird flu in the towns of Jaen and San Isidro in Nueva Ecija . After the strain of the bird flu was confirmed to be H5N6 which can be transmitted to humans, it was reported on August 25, that Department of Health is monitoring 34 farm workers in Nueva Ecija and Pampanga as suspected human cases of the disease. Agriculture Secretary Piñol declared the outbreak officially over on September 2, 2017, and eased quarantine measures. The strain of the avian influenza virus is not of the H5N1 strain according to the Research Institute for Tropical Medicine which conducted testings on samples of the virus from infected birds. The samples were sent to Australia where the Australian Animal Health Laboratory determined the exact strain of the virus. In the latter part of August 2017, the samples tested positive for H5N6 subtype. H5N6 can be transmitted to humans although it is less infectious and less fatal compared to the deadlier H5N1 strain. The Philippines government has prepared a manual dating back as early as 2004 which tackles on dealing with an avian influenza (AI) outbreak in the country. Under the manual there are four possible stages of occurrence of bird flu in the country. an AI-free nation AI outbreak in poultry AI transmission from poultry to humans AI transmission among humans The Philippines has been under stage 1 until the bird flu situation in the country was raised to stage 2 following the confirmation of the outbreak which started in Pampanga. A quarantine zone was imposed centering Barangay San Carlos of San Luis which covered an area 1 kilometer (0.62 mi) . The quarantine radius covers five barangays in San Luis, Mexico and Santa Ana towns. Within the quarantine zone a total of 200 thousand birds wild or domesticated will be culled during a three-day period. The corpses will be buried in a highly elevated place. Animals within the designated area will be quarantined for 90 days while those in the surrounding area will be quarantined for 21 days. The quarantine zone was extended as far as 7 kilometers (4.3 mi) and was also imposed in Jaen and San Isidro, Nueva Ecija. This zone was reduced back to 1 kilometer on August 31, 2017. 500 soldiers has been mobilized to aid the culling efforts. By August 25, more than 470 thousand chickens, ducks, and quails has been culled. By September 2017, more than 600 thousand birds have been culled. Through a circular dated on August 11, 2017, the Department of Agriculture imposed a temporary ban against transporting birds and poultry products from Pampanga to other parts of Luzon as well as banned the transfer of live poultry and poultry products from Luzon to Visayas and Mindanao to prevent the spread of the disease. After consulting with biosecurity experts, the ban was partially lifted by August 23 but the transport of poultry from within the quarantine areas centered on affected towns in Pampanga and Nueva Ecija remains. A quarantine zone was imposed centering Barangay San Carlos of San Luis which covered an area 1 kilometer (0.62 mi) . The quarantine radius covers five barangays in San Luis, Mexico and Santa Ana towns. Within the quarantine zone a total of 200 thousand birds wild or domesticated will be culled during a three-day period. The corpses will be buried in a highly elevated place. Animals within the designated area will be quarantined for 90 days while those in the surrounding area will be quarantined for 21 days. The quarantine zone was extended as far as 7 kilometers (4.3 mi) and was also imposed in Jaen and San Isidro, Nueva Ecija. This zone was reduced back to 1 kilometer on August 31, 2017. 500 soldiers has been mobilized to aid the culling efforts. By August 25, more than 470 thousand chickens, ducks, and quails has been culled. By September 2017, more than 600 thousand birds have been culled. Through a circular dated on August 11, 2017, the Department of Agriculture imposed a temporary ban against transporting birds and poultry products from Pampanga to other parts of Luzon as well as banned the transfer of live poultry and poultry products from Luzon to Visayas and Mindanao to prevent the spread of the disease. After consulting with biosecurity experts, the ban was partially lifted by August 23 but the transport of poultry from within the quarantine areas centered on affected towns in Pampanga and Nueva Ecija remains. It is yet to be determined how avian influenza was successfully transmitted to the Philippines. The Department of Agriculture either suspects that the virus was transmitted by migratory birds or through the smuggling of Peking Ducks through Subic Port . The farm where the avian flu originated had a practice of setting up quails above ducks. The outbreak caused a drop of the farm gate prices of poultry. The prices dropped to ₱10 to ₱15 per kilogram ( ₱4.5 to ₱6.8 per pound) from the average price of ₱70 per kilogram ( ₱31.75 per pound). The poultry industry has estimated that it suffered a ₱179 million loss per day. As of August 23, 2017, the outbreak already costed the country's poultry industry ₱2.3 billion . Samahang Industriya ng Agrikultura (SINAG), an agriculture group, called for the Department of Agriculture 's response to the incident to be more discreet saying that their handling of the outbreak has "over reaction" from the public. With the outbreak still officially limited to a single municipality at the time SINAG issued the statement, the group said that the outbreak is not "in magnitude, value, and volume" and the DA could have just said that the occurrence is an isolated case. SINAG suspected that the DA may intend to "wantonly" import poultry abroad which the group says is a response to a "common chorus of an impending shortage". It called for a ban import of poultry from other countries which it deems to have worse or longer bird flu occurrences. It alleged that there is leniency to import poultry abroad and laments that the local poultry industry "always" had to suffer. It called for the lifting of the ban of transporting poultry from Luzon to the rest of the country. They welcomed the easing of the quarantine measures on August 31, 2017. The Jollibee Foods Corporation and McDonald's Philippines had issued statements that their product are safe to eat amidst the outbreak. The governments of Japan , Saudi Arabia , South Korea , and Singapore has imposed a ban on importing poultry from the Philippines to their country as countermeasures against the disease. Samahang Industriya ng Agrikultura (SINAG), an agriculture group, called for the Department of Agriculture 's response to the incident to be more discreet saying that their handling of the outbreak has "over reaction" from the public. With the outbreak still officially limited to a single municipality at the time SINAG issued the statement, the group said that the outbreak is not "in magnitude, value, and volume" and the DA could have just said that the occurrence is an isolated case. SINAG suspected that the DA may intend to "wantonly" import poultry abroad which the group says is a response to a "common chorus of an impending shortage". It called for a ban import of poultry from other countries which it deems to have worse or longer bird flu occurrences. It alleged that there is leniency to import poultry abroad and laments that the local poultry industry "always" had to suffer. It called for the lifting of the ban of transporting poultry from Luzon to the rest of the country. They welcomed the easing of the quarantine measures on August 31, 2017. The Jollibee Foods Corporation and McDonald's Philippines had issued statements that their product are safe to eat amidst the outbreak. The governments of Japan , Saudi Arabia , South Korea , and Singapore has imposed a ban on importing poultry from the Philippines to their country as countermeasures against the disease. The Department of Agriculture declared that they were able to "effectively contain" the outbreak. The government body will conduct a post-crisis analysis with poultry stakeholders where the DA will suggest greater bio-security measure in farms in the country. Agriculture Secretary Piñol said that many of the farms he visited in Pampanga lacked "basic bio-security facilities, like a simple footbath and vehicle disinfection facility" and a "disposal area for dead fowls or wastes within the farm area". The incident is also cited as one of the major reason to loan a pair of Philippine eagles to Singapore as part of a conservation effort for the species. The move was to ensure that the Philippine eagle won't be rendered extinct in case of a similar incident to the 2017 outbreak would wipe out the eagle's population of the Philippines.

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Avian influenza

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Hong Kong flu

The Hong Kong flu , also known as the 1968 flu pandemic , was a flu pandemic that occurred in 1968 and 1969 and which killed between one and four million people globally. It is among the deadliest pandemics in history, and was caused by an H3N2 strain of the influenza A virus . The virus was descended from H2N2 (which caused the Asian flu pandemic in 1957–1958) through antigenic shift , a genetic process in which genes from multiple subtypes are reassorted to form a new virus. The first recorded instance of the outbreak appeared on 13 July 1968 in British Hong Kong . It has been speculated that the outbreak began in mainland China before it spread to Hong Kong; On 11 July, before the outbreak in the colony was first noted, the Hong Kong newspaper Ming Pao reported an outbreak of respiratory illness in Guangdong Province , and the next day, The Times issued a similar report of an epidemic in southeastern China. Later reporting suggested that the flu had spread from the central provinces of Sichuan , Gansu , Shaanxi , and Shanxi , which had experienced epidemics in the spring. However, due to a lack of etiological information on the outbreak and a strained relationship between Chinese health authorities and those in other countries at the time, it cannot be ascertained whether the Hong Kong virus was to blame. The outbreak in Hong Kong, where the population density was greater than 6,000 people per square kilometre (20,000 per sq. mi.), [ clarify ] reached its maximum intensity in two weeks. The outbreak lasted around six weeks, affecting about 15% of the population (some 500,000 people infected), but the mortality rate was low and the clinical symptoms were mild. There were two waves of the flu in mainland China, one between July–September in 1968 and the other between June–December in 1970. The reported data were very limited due to the Cultural Revolution , but retrospective analysis of flu activity between 1968 and 1992 shows that flu infection was the most serious in 1968, implying that most areas in China were affected at the time. Despite the lethality of the 1957–1958 pandemic in China , little improvement had been made regarding the handling of such epidemics. By 13 August, it was clear to virologists that strains isolated from the outbreak in Hong Kong differed markedly from previous strains of influenza. However, they were not at the time considered to be an entirely new subtype of influenza A, only a variant of older strains. Nevertheless, the World Health Organization warned of potential worldwide spread of the virus on 16 August. An outbreak of influenza-like illness in Singapore during the second week of August was the first indication of spread outside of Hong Kong. Around the same time, an outbreak became apparent in the Philippines and Malaysia , and, before the end of the month, an epidemic was underway in the Republic of Vietnam . The first known cases of the flu in the United Kingdom were identified in early August in an infant and her mother in London with no history of travel or known contact with anyone with a history of travel from the Far East. More isolated cases soon followed, but it was not until September that larger outbreaks began occurring in school settings. In September 1968, the flu reached India , northern Australia , Thailand , and Europe . The same month, the virus entered the United States and was carried by troops returning from the Vietnam War , but it did not become widespread in the country until December 1968. During the second week of September, nearly 2000 participants from 92 countries, including some in southeast Asia where the flu was epidemic, met in Tehran for the Eighth International Congresses on Tropical Medicine and Malaria. An outbreak of influenza soon erupted among the participants, afflicting at least a third of them. The convention was the apparent origin of a broader outbreak within the capital city, which thereafter spread rapidly throughout Iran . The virus entered Japan repeatedly throughout August and September, but these introductions did not spark any larger outbreak. The first "true epidemic" began in early October, almost entirely confined to school settings. In the USSR , the first cases of the flu began to appear in mid-December. It reached Africa and South America by 1969. The development of the pandemic at first resembled that of the 1957 pandemic, which had spread unencumbered throughout the spring and summer and had become truly worldwide by October, by which point nearly all countries were experiencing their first or even second wave. However, the two experiences eventually diverged within a couple of months after their initial outbreaks. In 1968, many countries (e.g., the UK, Japan) did not immediately see outbreaks despite repeated introductions of the virus throughout August and September. Additionally, after September, there was little evidence of continued spread in new areas, despite similar importations of the virus into those areas. Epidemics did eventually develop during the winter months, but these were often mild (especially when compared to the US experience). In some countries (such as the UK and Japan), it was not until the following winter of 1969–1970 that truly severe epidemics developed. At the time of the outbreak, the Hong Kong flu was also known as the "Mao flu" or " Mao Tse-tung flu". The name "Hong Kong flu" was not used within the colony, where the press dubbed it the "killer flu" after the first several deaths. Before the end of July, the South China Morning Post predicted that "Fingers of scorn" would be directed at Hong Kong in the coming weeks and stated that the colony had "acted, unwillingly, in our old role as an entrepot for a sneeze". (An outbreak of influenza in Hong Kong had been the first one to occur outside of mainland China during the 1957–1958 pandemic and had been what alerted the rest of the world to the developing situation, when international press began to report on it.) A city councillor [ who? ] later decried the widespread adoption of the name "Hong Kong flu", claiming that it was "giving Hong Kong a bad name". He asked why foreign press and health authorities did not refer to it by its "proper name—China flu". China certainly did not escape associations with the new virus, however, as the name "Mao flu" suggests. It was speculated even at the time that the virus had originated from "Red China". These differing names for the flu resulted in some confusion: In January 1969, a British member of parliament asked David Ennals , the Secretary of State for Social Services , "in what way the characteristics of Mao flu can be distinguished from those of Hong Kong flu". In addition to these names, the virus was also often referred to as "Asian flu" or "Asiatic flu", as it was not yet considered an entirely different subtype from the previously circulating influenza A. Worldwide deaths from the virus peaked in December 1968 and January 1969, when public health warnings and virus descriptions had been widely issued in the scientific and medical journals. Isolated countries like Albania reported the first cases of the flu in December 1969, reaching a peak in infections in the first months of the year 1970. In Berlin , the excessive number of deaths led to corpses being stored in subway tunnels, and in West Germany , garbage collectors had to bury the dead because of a lack of undertakers. In total, East and West Germany registered 60,000 estimated deaths. In some areas of France , half of the workforce was bedridden, and manufacturing suffered large disruptions because of absenteeism. The UK postal and rail services were also severely disrupted. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. It became apparent once the extent of antigenic variation in the virus was recognized that a new vaccine would be needed to protect against it. However, production of the previously recommended vaccines in the US had concluded by July 1968, and supply of fertilized chicken eggs, in which flu vaccines are grown , was limited. The first cultures of the virus were provided to manufacturers in August by the Division of Biologics of the National Institutes of Health for preliminary study. A strain isolated in Japan was sent to the US and, after showing greater potential for vaccine production, was given to manufacturers on 9 September. In 1968, American microbiologist Maurice Hilleman was head of the virus and vaccination research programs at the pharmaceutical firm Merck & Co. , one of the licensed vaccine manufacturers in the US. Hilleman, as the director of the Department of Respiratory Diseases at the Army Medical School (now the Walter Reed Army Institute of Research ), had foreseen the 1957 pandemic and kickstarted vaccine production then. He was similarly instrumental in the development of the 1968 pandemic vaccine and, with the use of the Japanese strain, helped initiate early production. Merck would go on to produce over 9 million of the nearly 21 million doses of vaccine produced. The other half was produced together by Eli Lilly & Co. , Lederle Laboratories , Parke Davis & Co. , the National Drug Company, and Wyeth Laboratories . All of these except Wyeth had been involved in the production of the 1957 vaccine. On 15 November, 66 days after the production strain became available, the first batch of 110,000 doses of vaccine was released, most of which went to the Armed Forces . This represented a quicker turnaround than the release of the first doses of the 1957 vaccine, which took three months after its production strain became available. At this time, the flu was spreading fast around the country. There was much interest within the press and among public figures in the vaccine. On 18 November, the Pharmaceutical Manufacturers Association announced that 17.5 million doses would be available for civilian use but said that "substantial quantities" would only come after the New Year. By the end of the year, over 10 million doses had been released. At this point, influenza was widespread in the country. Notably, the crew of Apollo 8 received the vaccine on 3 December prior to their mission later in the month. President Johnson received "two types" of vaccine prior to his bout of flu in December, but it is not clear if one of these was the pandemic vaccine. Johnson, 60 at the time, was in poor health and had been hospitalized several times during his presidency. He thus would have been prioritized for vaccine given the CDC recommendations, even outside of being the president. Lots of vaccine continued to be released throughout January 1969, with nearly 21 million doses available by the end of the month. By this point, however, influenza activity and subsequent mortality had already peaked. Demand for the vaccine diminished and a considerable surplus remained. Given the time it took to build up antibodies, it is unlikely a significant number of people were effectively immunized to alter the course of the epidemic. Hilleman himself would later acknowledge that the vaccine was "too little and too late" for most of the country. However, it was estimated that a "considerably higher" proportion of the recommended priority group of older and chronically ill persons received the pandemic vaccine than in 1957. Nevertheless, even after the debacle that was the vaccination effort in 1957 , US health officials by 1968 still had "no meaningful information regarding [influenza vaccine's] actual distribution", such as "to what extent it actually reaches persons at highest risk." Following the epidemic in the US, leftover vaccine was made available for the southern hemisphere and parts of Europe where the main outbreak had not yet happened. The Japanese strain of the new variant was incorporated into the bivalent vaccines recommended for the 1969–1970 flu season in the US. Outside the US, vaccination efforts were undertaken in many countries in anticipation of an epidemic. In contrast to US policy, Japan had, since 1963, carried out mass vaccination campaigns against influenza every year regardless of whether an epidemic was expected. This began with the immunization of all children in kindergartens and primary and secondary schools followed by the vaccination of those working in crowded conditions. Enough vaccine was produced each year to vaccinate about 24 million people (nearly a quarter of Japan's population at this time), and this became the goal in 1968, targeting the same priority groups as in a typical flu season. The same Japanese strain used for vaccine production in the US was immediately sent out to the seven manufacturing firms in Japan. It was soon decided a bivalent vaccine consisting of two parts the new variant and one part influenza B would be produced, in contrast to the US's use of monovalent vaccine. The objective was also set that enough vaccine to immunize about 12 million people would be produced by the end of October, with the hope of at least vaccinating children to guard against an epidemic developing out of schools. After some delay, the mass vaccination campaign was nearly completed before the end of the year. Yugoslavia received the Japanese strain in mid-October and immediately began experimental trials prior to large-scale production. During this time before the new vaccine was ready, 1.5 million doses of seasonal influenza A vaccine were distributed for use. Ten million doses of the pandemic vaccine had been produced by mid-January 1969, and nearly 1 million people were immunized before the end of February. About 100,000 doses were designated for the mass immunization of schoolchildren. In Denmark , the influenza department at the governmental Statens Serum Institut produced about 200,000 doses of pandemic vaccine during the winter of 1968–1969, incorporating a strain isolated in Stockholm . There were no particular difficulties in production, but yield was poor. Millions of doses of vaccine were available in South Africa before its epidemic began at the end of March 1969, which afforded the opportunity to perform "limited studies" of its effectiveness. By January 1969, vaccine production in Australia was underway at the Commonwealth Serum Laboratories (CSL), then a department of the federal government . The trivalent pandemic vaccine, composed of two influenza A strains and a B strain, was anticipated for release in early March ahead of the winter flu season. The inoculation consisted of a two-dose series, each given four weeks apart. CSL was aggressive in its promotion of the vaccine, at least to doctors. A spokesman for the laboratories described the new virus as "the worst flu we have had" and called an epidemic that year "almost certain". In light of the situation, the Australian Pensioners Federation in early January wrote to Minister for Health Jim Forbes "demanding" that the vaccine be given free of charge to pensioners. In contrast to CSL's bolder predictions, Forbes described an outbreak that winter as "possible" but did not think it would "necessarily be serious or extensive". While the Department of Health reviewed the question of pandemic vaccine allocation in Australia, the government exported 1 million doses of its vaccine to Britain, already at the peak of its epidemic. In early February, the epidemiology committee of Australia's National Health and Medical Research Council met in Melbourne to discuss the influenza threat and the best use of vaccine the coming winter. A "serious epidemic" was considered the "strongest possibility", and it was recommended to Forbes that older people, children, and pregnant women receive free immunization against the flu. However, the council advised against a mass vaccination campaign, citing the findings of its study which showed the unreliable protection against infection of the present vaccines, and considered it unwise to vaccinate healthy people while the limited supply could be better used to mitigate severe outcomes in at-risk groups. On the last day of February, the Pharmaceutical Benefits Advisory Committee met to consider the question of making the pandemic vaccine a pharmaceutical benefit for pensioners. Before the end of the week, Forbes announced that shots would be given for free to all pensioners and their dependents, representing about two-thirds of the three groups recommended for priority immunization. The policy would go into effect starting 1 April. Vaccination against the flu was recommended beginning 1 March, but issues surrounding availability of vaccine soon became apparent throughout the month. In response to Representative Gordon Scholes of Victoria , who had heard complaints from chemists unable to acquire vaccine, Forbes clarified that bulk orders from larger establishments would be met first. He relayed the expectation of the director of CSL that the present situation would be met once quantities of single doses became available in early April. In the middle of March, Forbes assured that all medical practitioners would be able to acquire the vaccine by the middle of April. He described the new type of flu as milder than that which Australia had typically seen each year. Representative Charles Jones of Newcastle later in the month questioned Forbes why his home city's order had not been filled. Forbes revealed the export of 1 million doses to Britain earlier in the year but assured that the order "did not delay, or in any way hinder, [the Commonwealth Serum Laboratories'] capacity to fill Australian orders" and that there would be enough supply to meet expected demand. By this time, 1,755,000 doses had been released, and production continued its pace of 200,000 doses per week. Despite these assurances from Forbes, the Director General of the Department of Health William Refshauge sent a letter on 9 April to all doctors in the country asking them not to vaccinate healthy people until at-risk groups in the community have been inoculated. Forbes reported meeting with the Commonwealth Serum Laboratories commission to discuss how to speed up distribution of vaccine. Two days later, the director of CSL, W. R. Lane, dismissed criticism of the supply situation from the New South Wales branch of the Australian Medical Association as "a lot of nonsense". Contradicting the laboratories' more forceful marketing earlier in the year, he downplayed the likelihood of a serious epidemic but shared the expectation of 4 million doses distributed by the end of May, eight times as much as the average annual total distribution of 500,000 vaccine doses. On 22 April, Forbes testified in the House of Representatives regarding the vaccine situation. He reported 2.5 million doses had been produced by this time since February. When asked by Representative Theo Nicholls of South Australia to consider importing vaccine to alleviate the present shortage, Forbes noted that the country had already imported the 150,000 doses available. He lamented CSL's recent subjection to a "good deal of abuse" regarding the "temporary shortages" around the country, repeating the comparison between the present production effort and the country's average annual distribution of only 500,000 doses. That same day, N. F. Keith, president of the Victorian branch of the Pharmacy Guild , called on CSL to explain the situation surrounding vaccine supply to the public, which was putting pressure on chemists due to the lack of vaccines. On 25 April, it was reported that the Department of Health had reimported the remaining vaccine from the order of 1 million that the government had exported to Britain in January. After being sent to Britain, packaged there, and then sent back to Australia, it was sold to doctors at a markup of nearly 50 percent. Doctors criticized the Department and CSL's poor planning with respect to vaccine supply and the decision to export vaccine to Britain when it had already reached the peak of its flu season. They also blamed the shortage on an overreaction by the public, a response which they considered largely due to public statements made by CSL and health officials. The Department later attributed the decision to reimport the vaccine to a desire to ensure a reliable supply for pensioners. It also denied any involvement in the commercial sales of vaccine, in response to reporting on price markups on the reimported vaccine, saying that all it did was authorize the reimportation and list the product as a pharmaceutical benefit. The government itself was paying the same for the reimported vaccine as it was for that being distributed by CSL. By the end of April, 2.8 million doses of vaccine had been produced and distributed, with no signs of production slowing down. 250,000 doses were now being produced each week, and nearly half a million more were anticipated for 2 May. The H3N2 virus displaced the previously circulating H2N2 virus, which first emerged in 1957, and returned during the following 1969–70 flu season, which resulted in a second, deadlier wave of deaths in Europe, Japan, and Australia. Following the season of intense activity in many countries in the Southern Hemisphere, there was relatively low incidence of flu the subsequent two global flu seasons, from October 1970 to September 1971. Influenza B was predominant in the north, causing extensive outbreaks in the United States, but minimal in the south. The Hong Kong virus, on the other hand, was responsible for some large outbreaks in the Southern Hemisphere, some most likely occurring in populations that had still not been exposed to the virus. It was during this period that the city of Coonoor , in India, experienced a "fairly extensive" outbreak, in July 1971. Samples of the virus responsible were collected but their significance was not immediately recognized. The virus did not immediately spread to other countries, or at least did not immediately cause outbreaks, but it was amid an epidemic in England in early 1972, fueled by more original strains, that a variant showing considerable antigenic drift was identified in one isolate tested out of over 700. It ultimately came to be designated A/England/42/72. It was soon recognized, by comparison with the strains isolated then, that this virus had been the one responsible for the epidemic in India. The novel variant did not immediately spread after that outbreak, and circulating strains largely continued to resemble quite closely the original Hong Kong virus through April 1972. In May, however, at the onset of the flu season in the Southern Hemisphere, epidemics caused by the variant struck Malaysia, Singapore, and Australia, though South Africa and South America were unaffected. The die seemingly cast, the novel variant went on to cause widespread outbreaks in the Northern Hemisphere, by which point US press had dubbed the bug " London flu ". It completely replaced the previous strains still resembling the original pandemic virus. In places such as the US and England and Wales, the 1972–1973 flu season was the deadliest since their respective deadliest waves of the pandemic between 1968 and 1970. Influenza A/H3N2 remains in circulation today as a strain of seasonal flu. The first recorded instance of the outbreak appeared on 13 July 1968 in British Hong Kong . It has been speculated that the outbreak began in mainland China before it spread to Hong Kong; On 11 July, before the outbreak in the colony was first noted, the Hong Kong newspaper Ming Pao reported an outbreak of respiratory illness in Guangdong Province , and the next day, The Times issued a similar report of an epidemic in southeastern China. Later reporting suggested that the flu had spread from the central provinces of Sichuan , Gansu , Shaanxi , and Shanxi , which had experienced epidemics in the spring. However, due to a lack of etiological information on the outbreak and a strained relationship between Chinese health authorities and those in other countries at the time, it cannot be ascertained whether the Hong Kong virus was to blame. The outbreak in Hong Kong, where the population density was greater than 6,000 people per square kilometre (20,000 per sq. mi.), [ clarify ] reached its maximum intensity in two weeks. The outbreak lasted around six weeks, affecting about 15% of the population (some 500,000 people infected), but the mortality rate was low and the clinical symptoms were mild. There were two waves of the flu in mainland China, one between July–September in 1968 and the other between June–December in 1970. The reported data were very limited due to the Cultural Revolution , but retrospective analysis of flu activity between 1968 and 1992 shows that flu infection was the most serious in 1968, implying that most areas in China were affected at the time. Despite the lethality of the 1957–1958 pandemic in China , little improvement had been made regarding the handling of such epidemics. By 13 August, it was clear to virologists that strains isolated from the outbreak in Hong Kong differed markedly from previous strains of influenza. However, they were not at the time considered to be an entirely new subtype of influenza A, only a variant of older strains. Nevertheless, the World Health Organization warned of potential worldwide spread of the virus on 16 August. An outbreak of influenza-like illness in Singapore during the second week of August was the first indication of spread outside of Hong Kong. Around the same time, an outbreak became apparent in the Philippines and Malaysia , and, before the end of the month, an epidemic was underway in the Republic of Vietnam . The first known cases of the flu in the United Kingdom were identified in early August in an infant and her mother in London with no history of travel or known contact with anyone with a history of travel from the Far East. More isolated cases soon followed, but it was not until September that larger outbreaks began occurring in school settings. In September 1968, the flu reached India , northern Australia , Thailand , and Europe . The same month, the virus entered the United States and was carried by troops returning from the Vietnam War , but it did not become widespread in the country until December 1968. During the second week of September, nearly 2000 participants from 92 countries, including some in southeast Asia where the flu was epidemic, met in Tehran for the Eighth International Congresses on Tropical Medicine and Malaria. An outbreak of influenza soon erupted among the participants, afflicting at least a third of them. The convention was the apparent origin of a broader outbreak within the capital city, which thereafter spread rapidly throughout Iran . The virus entered Japan repeatedly throughout August and September, but these introductions did not spark any larger outbreak. The first "true epidemic" began in early October, almost entirely confined to school settings. In the USSR , the first cases of the flu began to appear in mid-December. It reached Africa and South America by 1969. The development of the pandemic at first resembled that of the 1957 pandemic, which had spread unencumbered throughout the spring and summer and had become truly worldwide by October, by which point nearly all countries were experiencing their first or even second wave. However, the two experiences eventually diverged within a couple of months after their initial outbreaks. In 1968, many countries (e.g., the UK, Japan) did not immediately see outbreaks despite repeated introductions of the virus throughout August and September. Additionally, after September, there was little evidence of continued spread in new areas, despite similar importations of the virus into those areas. Epidemics did eventually develop during the winter months, but these were often mild (especially when compared to the US experience). In some countries (such as the UK and Japan), it was not until the following winter of 1969–1970 that truly severe epidemics developed. At the time of the outbreak, the Hong Kong flu was also known as the "Mao flu" or " Mao Tse-tung flu". The name "Hong Kong flu" was not used within the colony, where the press dubbed it the "killer flu" after the first several deaths. Before the end of July, the South China Morning Post predicted that "Fingers of scorn" would be directed at Hong Kong in the coming weeks and stated that the colony had "acted, unwillingly, in our old role as an entrepot for a sneeze". (An outbreak of influenza in Hong Kong had been the first one to occur outside of mainland China during the 1957–1958 pandemic and had been what alerted the rest of the world to the developing situation, when international press began to report on it.) A city councillor [ who? ] later decried the widespread adoption of the name "Hong Kong flu", claiming that it was "giving Hong Kong a bad name". He asked why foreign press and health authorities did not refer to it by its "proper name—China flu". China certainly did not escape associations with the new virus, however, as the name "Mao flu" suggests. It was speculated even at the time that the virus had originated from "Red China". These differing names for the flu resulted in some confusion: In January 1969, a British member of parliament asked David Ennals , the Secretary of State for Social Services , "in what way the characteristics of Mao flu can be distinguished from those of Hong Kong flu". In addition to these names, the virus was also often referred to as "Asian flu" or "Asiatic flu", as it was not yet considered an entirely different subtype from the previously circulating influenza A. Worldwide deaths from the virus peaked in December 1968 and January 1969, when public health warnings and virus descriptions had been widely issued in the scientific and medical journals. Isolated countries like Albania reported the first cases of the flu in December 1969, reaching a peak in infections in the first months of the year 1970. In Berlin , the excessive number of deaths led to corpses being stored in subway tunnels, and in West Germany , garbage collectors had to bury the dead because of a lack of undertakers. In total, East and West Germany registered 60,000 estimated deaths. In some areas of France , half of the workforce was bedridden, and manufacturing suffered large disruptions because of absenteeism. The UK postal and rail services were also severely disrupted. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. It became apparent once the extent of antigenic variation in the virus was recognized that a new vaccine would be needed to protect against it. However, production of the previously recommended vaccines in the US had concluded by July 1968, and supply of fertilized chicken eggs, in which flu vaccines are grown , was limited. The first cultures of the virus were provided to manufacturers in August by the Division of Biologics of the National Institutes of Health for preliminary study. A strain isolated in Japan was sent to the US and, after showing greater potential for vaccine production, was given to manufacturers on 9 September. In 1968, American microbiologist Maurice Hilleman was head of the virus and vaccination research programs at the pharmaceutical firm Merck & Co. , one of the licensed vaccine manufacturers in the US. Hilleman, as the director of the Department of Respiratory Diseases at the Army Medical School (now the Walter Reed Army Institute of Research ), had foreseen the 1957 pandemic and kickstarted vaccine production then. He was similarly instrumental in the development of the 1968 pandemic vaccine and, with the use of the Japanese strain, helped initiate early production. Merck would go on to produce over 9 million of the nearly 21 million doses of vaccine produced. The other half was produced together by Eli Lilly & Co. , Lederle Laboratories , Parke Davis & Co. , the National Drug Company, and Wyeth Laboratories . All of these except Wyeth had been involved in the production of the 1957 vaccine. On 15 November, 66 days after the production strain became available, the first batch of 110,000 doses of vaccine was released, most of which went to the Armed Forces . This represented a quicker turnaround than the release of the first doses of the 1957 vaccine, which took three months after its production strain became available. At this time, the flu was spreading fast around the country. There was much interest within the press and among public figures in the vaccine. On 18 November, the Pharmaceutical Manufacturers Association announced that 17.5 million doses would be available for civilian use but said that "substantial quantities" would only come after the New Year. By the end of the year, over 10 million doses had been released. At this point, influenza was widespread in the country. Notably, the crew of Apollo 8 received the vaccine on 3 December prior to their mission later in the month. President Johnson received "two types" of vaccine prior to his bout of flu in December, but it is not clear if one of these was the pandemic vaccine. Johnson, 60 at the time, was in poor health and had been hospitalized several times during his presidency. He thus would have been prioritized for vaccine given the CDC recommendations, even outside of being the president. Lots of vaccine continued to be released throughout January 1969, with nearly 21 million doses available by the end of the month. By this point, however, influenza activity and subsequent mortality had already peaked. Demand for the vaccine diminished and a considerable surplus remained. Given the time it took to build up antibodies, it is unlikely a significant number of people were effectively immunized to alter the course of the epidemic. Hilleman himself would later acknowledge that the vaccine was "too little and too late" for most of the country. However, it was estimated that a "considerably higher" proportion of the recommended priority group of older and chronically ill persons received the pandemic vaccine than in 1957. Nevertheless, even after the debacle that was the vaccination effort in 1957 , US health officials by 1968 still had "no meaningful information regarding [influenza vaccine's] actual distribution", such as "to what extent it actually reaches persons at highest risk." Following the epidemic in the US, leftover vaccine was made available for the southern hemisphere and parts of Europe where the main outbreak had not yet happened. The Japanese strain of the new variant was incorporated into the bivalent vaccines recommended for the 1969–1970 flu season in the US. Outside the US, vaccination efforts were undertaken in many countries in anticipation of an epidemic. In contrast to US policy, Japan had, since 1963, carried out mass vaccination campaigns against influenza every year regardless of whether an epidemic was expected. This began with the immunization of all children in kindergartens and primary and secondary schools followed by the vaccination of those working in crowded conditions. Enough vaccine was produced each year to vaccinate about 24 million people (nearly a quarter of Japan's population at this time), and this became the goal in 1968, targeting the same priority groups as in a typical flu season. The same Japanese strain used for vaccine production in the US was immediately sent out to the seven manufacturing firms in Japan. It was soon decided a bivalent vaccine consisting of two parts the new variant and one part influenza B would be produced, in contrast to the US's use of monovalent vaccine. The objective was also set that enough vaccine to immunize about 12 million people would be produced by the end of October, with the hope of at least vaccinating children to guard against an epidemic developing out of schools. After some delay, the mass vaccination campaign was nearly completed before the end of the year. Yugoslavia received the Japanese strain in mid-October and immediately began experimental trials prior to large-scale production. During this time before the new vaccine was ready, 1.5 million doses of seasonal influenza A vaccine were distributed for use. Ten million doses of the pandemic vaccine had been produced by mid-January 1969, and nearly 1 million people were immunized before the end of February. About 100,000 doses were designated for the mass immunization of schoolchildren. In Denmark , the influenza department at the governmental Statens Serum Institut produced about 200,000 doses of pandemic vaccine during the winter of 1968–1969, incorporating a strain isolated in Stockholm . There were no particular difficulties in production, but yield was poor. Millions of doses of vaccine were available in South Africa before its epidemic began at the end of March 1969, which afforded the opportunity to perform "limited studies" of its effectiveness. By January 1969, vaccine production in Australia was underway at the Commonwealth Serum Laboratories (CSL), then a department of the federal government . The trivalent pandemic vaccine, composed of two influenza A strains and a B strain, was anticipated for release in early March ahead of the winter flu season. The inoculation consisted of a two-dose series, each given four weeks apart. CSL was aggressive in its promotion of the vaccine, at least to doctors. A spokesman for the laboratories described the new virus as "the worst flu we have had" and called an epidemic that year "almost certain". In light of the situation, the Australian Pensioners Federation in early January wrote to Minister for Health Jim Forbes "demanding" that the vaccine be given free of charge to pensioners. In contrast to CSL's bolder predictions, Forbes described an outbreak that winter as "possible" but did not think it would "necessarily be serious or extensive". While the Department of Health reviewed the question of pandemic vaccine allocation in Australia, the government exported 1 million doses of its vaccine to Britain, already at the peak of its epidemic. In early February, the epidemiology committee of Australia's National Health and Medical Research Council met in Melbourne to discuss the influenza threat and the best use of vaccine the coming winter. A "serious epidemic" was considered the "strongest possibility", and it was recommended to Forbes that older people, children, and pregnant women receive free immunization against the flu. However, the council advised against a mass vaccination campaign, citing the findings of its study which showed the unreliable protection against infection of the present vaccines, and considered it unwise to vaccinate healthy people while the limited supply could be better used to mitigate severe outcomes in at-risk groups. On the last day of February, the Pharmaceutical Benefits Advisory Committee met to consider the question of making the pandemic vaccine a pharmaceutical benefit for pensioners. Before the end of the week, Forbes announced that shots would be given for free to all pensioners and their dependents, representing about two-thirds of the three groups recommended for priority immunization. The policy would go into effect starting 1 April. Vaccination against the flu was recommended beginning 1 March, but issues surrounding availability of vaccine soon became apparent throughout the month. In response to Representative Gordon Scholes of Victoria , who had heard complaints from chemists unable to acquire vaccine, Forbes clarified that bulk orders from larger establishments would be met first. He relayed the expectation of the director of CSL that the present situation would be met once quantities of single doses became available in early April. In the middle of March, Forbes assured that all medical practitioners would be able to acquire the vaccine by the middle of April. He described the new type of flu as milder than that which Australia had typically seen each year. Representative Charles Jones of Newcastle later in the month questioned Forbes why his home city's order had not been filled. Forbes revealed the export of 1 million doses to Britain earlier in the year but assured that the order "did not delay, or in any way hinder, [the Commonwealth Serum Laboratories'] capacity to fill Australian orders" and that there would be enough supply to meet expected demand. By this time, 1,755,000 doses had been released, and production continued its pace of 200,000 doses per week. Despite these assurances from Forbes, the Director General of the Department of Health William Refshauge sent a letter on 9 April to all doctors in the country asking them not to vaccinate healthy people until at-risk groups in the community have been inoculated. Forbes reported meeting with the Commonwealth Serum Laboratories commission to discuss how to speed up distribution of vaccine. Two days later, the director of CSL, W. R. Lane, dismissed criticism of the supply situation from the New South Wales branch of the Australian Medical Association as "a lot of nonsense". Contradicting the laboratories' more forceful marketing earlier in the year, he downplayed the likelihood of a serious epidemic but shared the expectation of 4 million doses distributed by the end of May, eight times as much as the average annual total distribution of 500,000 vaccine doses. On 22 April, Forbes testified in the House of Representatives regarding the vaccine situation. He reported 2.5 million doses had been produced by this time since February. When asked by Representative Theo Nicholls of South Australia to consider importing vaccine to alleviate the present shortage, Forbes noted that the country had already imported the 150,000 doses available. He lamented CSL's recent subjection to a "good deal of abuse" regarding the "temporary shortages" around the country, repeating the comparison between the present production effort and the country's average annual distribution of only 500,000 doses. That same day, N. F. Keith, president of the Victorian branch of the Pharmacy Guild , called on CSL to explain the situation surrounding vaccine supply to the public, which was putting pressure on chemists due to the lack of vaccines. On 25 April, it was reported that the Department of Health had reimported the remaining vaccine from the order of 1 million that the government had exported to Britain in January. After being sent to Britain, packaged there, and then sent back to Australia, it was sold to doctors at a markup of nearly 50 percent. Doctors criticized the Department and CSL's poor planning with respect to vaccine supply and the decision to export vaccine to Britain when it had already reached the peak of its flu season. They also blamed the shortage on an overreaction by the public, a response which they considered largely due to public statements made by CSL and health officials. The Department later attributed the decision to reimport the vaccine to a desire to ensure a reliable supply for pensioners. It also denied any involvement in the commercial sales of vaccine, in response to reporting on price markups on the reimported vaccine, saying that all it did was authorize the reimportation and list the product as a pharmaceutical benefit. The government itself was paying the same for the reimported vaccine as it was for that being distributed by CSL. By the end of April, 2.8 million doses of vaccine had been produced and distributed, with no signs of production slowing down. 250,000 doses were now being produced each week, and nearly half a million more were anticipated for 2 May. The H3N2 virus displaced the previously circulating H2N2 virus, which first emerged in 1957, and returned during the following 1969–70 flu season, which resulted in a second, deadlier wave of deaths in Europe, Japan, and Australia. Following the season of intense activity in many countries in the Southern Hemisphere, there was relatively low incidence of flu the subsequent two global flu seasons, from October 1970 to September 1971. Influenza B was predominant in the north, causing extensive outbreaks in the United States, but minimal in the south. The Hong Kong virus, on the other hand, was responsible for some large outbreaks in the Southern Hemisphere, some most likely occurring in populations that had still not been exposed to the virus. It was during this period that the city of Coonoor , in India, experienced a "fairly extensive" outbreak, in July 1971. Samples of the virus responsible were collected but their significance was not immediately recognized. The virus did not immediately spread to other countries, or at least did not immediately cause outbreaks, but it was amid an epidemic in England in early 1972, fueled by more original strains, that a variant showing considerable antigenic drift was identified in one isolate tested out of over 700. It ultimately came to be designated A/England/42/72. It was soon recognized, by comparison with the strains isolated then, that this virus had been the one responsible for the epidemic in India. The novel variant did not immediately spread after that outbreak, and circulating strains largely continued to resemble quite closely the original Hong Kong virus through April 1972. In May, however, at the onset of the flu season in the Southern Hemisphere, epidemics caused by the variant struck Malaysia, Singapore, and Australia, though South Africa and South America were unaffected. The die seemingly cast, the novel variant went on to cause widespread outbreaks in the Northern Hemisphere, by which point US press had dubbed the bug " London flu ". It completely replaced the previous strains still resembling the original pandemic virus. In places such as the US and England and Wales, the 1972–1973 flu season was the deadliest since their respective deadliest waves of the pandemic between 1968 and 1970. Influenza A/H3N2 remains in circulation today as a strain of seasonal flu. Flu symptoms typically lasted four to five days, but some cases persisted for up to two weeks. The Hong Kong flu was the first known outbreak of the H3N2 strain, but there is serologic evidence of H3N1 infections in the late 19th century. The virus was isolated in Queen Mary Hospital . Soon after the initial outbreak in Hong Kong, the virus responsible was recognized to be antigenically distinct from the current influenza A strain in circulation (which at the time was called "A2") but was generally not considered an entirely new subtype. Analysis using the conventional techniques at the time revealed that it was indeed very different from older A2 viruses but also, at the same time, seemingly related to them, depending on one's reading of the data. Experiments involving newer methods of analysis soon identified another surface antigen, neuraminidase , in addition to hemagglutinin , which had already been recognized. It thus became clear that it was the hemagglutinin that had changed compared to older strains while the neuraminidase was identical. These findings, in part, prompted the World Health Organization in 1971 to revise its system of nomenclature for influenza viruses, taking into consideration both antigens. The novel virus was thereafter designated H3N2, indicating its partial similarity to H2N2 but also its antigenic distinction. The H3N2 pandemic flu strain contained genes from a low- pathogenicity avian influenza virus. Specifically, it had acquired a new hemagglutinin gene and a new PB1 gene, while it preserved the neuraminidase and five other genes from the preexisting human H2N2 strain. The new hemagglutinin helped H3N2 evade preexisting immunity in humans. It is possible that the new PB1 facilitated viral replication and human-to-human transmission. The new subtype arose in pigs coinfected with avian and human viruses and was soon transferred to humans. Swine were considered the original "intermediate host" for influenza because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (such as many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 , associated with the 1918 flu pandemic , may have been transmitted directly from birds to humans. Accumulated antibodies to the neuraminidase or internal proteins may have resulted in many fewer casualties than most other pandemics . However, cross-immunity within and between subtypes of influenza is poorly understood. [ citation needed ] The basic reproduction number of the flu in this period was estimated at 1.80. The estimates of the total death toll due to Hong Kong flu (from its beginning in July 1968 until the outbreak faded during the winter of 1969–70 ) vary: However, the death rate from the Hong Kong flu was lower than most other 20th-century pandemics. The World Health Organization estimated the case fatality rate of Hong Kong flu to be lower than 0.2%. The disease was allowed to spread through the population without restrictions on economic activity, and a vaccine created by American microbiologist Maurice Hilleman and his team became available four months after it had started. Fewer people died during this pandemic than in previous pandemics for several reasons: For this pandemic, there were two geographically distinct mortality patterns. In North America (the United States and Canada), the first pandemic season (1968–69) was more severe than the second (1969–70). In the "smoldering" pattern seen in Europe and Asia (United Kingdom, France, Japan, and Australia), the second pandemic season was two to five times more severe than the first. The United States health authorities estimated that about 34,000 to 100,000 people died in the US; most excess deaths were in those aged 65 and older. For this pandemic, there were two geographically distinct mortality patterns. In North America (the United States and Canada), the first pandemic season (1968–69) was more severe than the second (1969–70). In the "smoldering" pattern seen in Europe and Asia (United Kingdom, France, Japan, and Australia), the second pandemic season was two to five times more severe than the first. The United States health authorities estimated that about 34,000 to 100,000 people died in the US; most excess deaths were in those aged 65 and older.

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Agricultural policy

Agricultural policy describes a set of laws relating to domestic agriculture and imports of foreign agricultural products. Governments usually implement agricultural policies with the goal of achieving a specific outcome in the domestic agricultural product markets. Agricultural policies use predetermined goals, objectives and pathways set by an individual or government for the purpose of achieving a specified outcome, for the benefit of the individual(s), society and the nations' economy at large. Agricultural policies take into consideration the primary, secondary and tertiary processes in agricultural production. Outcomes can involve, for example, a guaranteed supply level, price stability, product quality, product selection, land use or employment. Agriculture has large impacts on climate change , estimated to be contributing 20–25% of global annual emissions as of 2010. Moreover, agriculture is highly vulnerable to the negative impacts of climate change, such as decreases in water access , geophysical processes such as ocean level rise and changing weather , and socioeconomic processes that affect farmers, many of whom are in subsistence economic conditions . In order for global climate change mitigation and adaptation to be effective a wide range of policies need to be implemented to reduce the risk of negative climate change impacts on agriculture and greenhouse gas emissions from the agriculture sector. [lower-alpha 1] An example of the breadth and types of agriculture policy concerns can be found in the Australian Bureau of Agricultural and Resource Economics article "Agricultural Economies of Australia and New Zealand" which says that the major challenges and issues faced by their industrial agriculture industry are: Policymakers working in poverty reduction in the agriculture sector assess, plan, or enact policies aimed to address the needs of persons living in poverty. Agriculture has been a critical driver of poverty reduction in most developing countries, particularly in rural areas. Approximately 80% of the world's impoverished population, who primarily reside in rural areas and earn their livelihood through farming, can benefit from agriculture in terms of poverty reduction, income generation, and food security. Fostering agricultural development is therefore a crucial element of agricultural policy in a developing country . In addition, a recent Natural Resource Perspective paper by the Overseas Development Institute found that good infrastructure , education and effective information services in rural areas were necessary to improve the chances of making agriculture work for the poor. During the 1980s and 1990s, there was a disregard for the agriculture sector among policymakers and investors, only regaining interest when the prices of staple food crops experienced a significant increase in the mid-2000s. As a result of agricultural policy neglect, there has been a scarcity of investment in infrastructure, which has hindered agricultural development and public goods, such as education, research and development and technology. Rural productive sectors and small agricultural enterprises suffer from market failures due to policies favouring urban areas and lending policies biased against small-scale agricultural firms. Neglect in implementing agriculture policy has been detected in several developing countries. In Indonesia, since the Asian Financial Crisis of 1997 to 1998, the government's agricultural policy has been closely concentrated on achieving price stability and self-sufficiency for import-competing commodities, such as palm oil, sugar and rice. International agencies such as the Food and Agriculture Organization (FAO), the World Bank , the International Fund for Agricultural Development (IFAD) and the Organisation for Economic Co-operation and Development (OECD), espouse the prioritisation of agricultural endeavours to support poverty reduction. The impact of agricultural policy on reducing poverty differs across countries and is influenced by a variety of factors, such as the level of government policy support, the degree of public and private investment in agriculture, the different types of agriculture, and the growth rates of agriculture parallel to non-agriculture sectors. In particular, investment in agricultural research and development has been shown to be highly influential on agricultural GDP growth and poverty reduction. Government policies play a key role in promoting agricultural activities, such as irrigation systems, roads and telecommunication systems, land reform, power in rural areas, fiscal support for research and development, pricing policies, assistance for new technologies, and markets for agricultural produce. Agricultural policies have contributed to meeting the goals related to increasing, diversifying, and improving agricultural production. Agricultural policies aimed at reducing poverty include India's Pradhan Mantri Fasal Bima Yojana , which offers crop insurance to farmers to protect them from weather-related uncertainties and potential crop failures. [ citation needed ] This initiative provides farmers with financial aid for crop loss, reducing the risk of falling into poverty. Rwanda's Crop Intensification Program is another example of such policy, which provides farmers with inputs like fertilisers, improved seeds, and pesticides, as well as training and technical support to help them adopt more efficient farming practices. However, for agricultural policies to contribute to poverty reduction, it is essential that they collaborate effectively and cohesively with other sectors, such as tourism, sustainable economy, and industry. The biosecurity concerns facing industrial agriculture can be illustrated by: the threat to poultry and humans from H5N1 ; possibly caused by the use of animal vaccines the threat to cattle and humans from bovine spongiform encephalopathy (BSE); possibly caused by the unnatural feeding of cattle to cattle to minimize costs the threat to industry profits from diseases like foot-and-mouth disease and citrus canker which increasing globalization makes harder to contain The use of animal vaccines can create new viruses that kill people and cause flu pandemic threats. H5N1 is an example of where this might have already occurred. According to the CDC article "H5N1 Outbreaks and Enzootic Influenza" by Robert G. Webster et al.: "Transmission of highly pathogenic H5N1 from domestic poultry back to migratory waterfowl in western China has increased the geographic spread. The spread of H5N1 and its likely reintroduction to domestic poultry increase the need for good agricultural vaccines. In fact, the root cause of the continuing H5N1 pandemic threat may be the way the pathogenicity of H5N1 viruses is masked by co-circulating influenza viruses or bad agricultural vaccines." Robert Webster explains: "If you use a good vaccine you can prevent the transmission within poultry and to humans. But if they have been using vaccines now [in China] for several years, why is there so much bird flu? There is bad vaccine that stops the disease in the bird but the bird goes on pooping out the virus and maintaining it and changing it. And I think this is what is going on in China. It has to be. Either there is not enough vaccine being used or there is substandard vaccine being used. Probably both. It's not just China. We can't blame China for substandard vaccines. I think there are substandard vaccines for influenza in poultry all over the world." In response to the same concerns, Reuters reports Hong Kong infectious disease expert Lo Wing-lok indicating that vaccines have to take top priority. Julie Hall, who is in charge of the WHO's outbreak response in China, claimed that China's vaccinations might be masking the virus. The BBC reported that Wendy Barclay, a virologist at the University of Reading, UK said: "The Chinese have made a vaccine based on reverse genetics made with H5N1 antigens, and they have been using it. There has been a lot of criticism of what they have done because they have protected their chickens against death from this virus but the chickens still get infected, and then you get the drift - the virus mutates in response to the antibodies - and now we have a situation where we have five or six 'flavours' of H5N1 out there." Bovine spongiform encephalopathy (BSE), commonly known as "mad cow disease", is a fatal, neurodegenerative disease of cattle , which infects by a mechanism that surprised biologists upon its discovery in the late 20th century. In the UK, the country worst affected, 179,000 cattle were infected and 4.4 million were killed as a precaution. The disease can be transmitted to human beings who eat or inhale material from infected carcasses. [ citation needed ] In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease's long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. A British inquiry into BSE concluded that the epidemic was caused by feeding cattle, who are normally herbivores , the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. The infectious agent is distinctive for the high temperatures it is able to survive; this contributed to the spread of the disease in Britain, which had reduced the temperatures used during its rendering process. Another contributory factor was the feeding of infected protein supplements to very young calves instead of milk from their mothers. Foot-and-mouth disease is a highly contagious and sometimes fatal viral disease of cattle and pigs . It can also infect deer , goats , sheep , and other bovids with cloven hooves , as well as elephants , rats , and hedgehogs . Humans are affected only very rarely. FMD occurs throughout much of the world, and while some countries have been free of FMD for some time, its wide host range and rapid spread represent cause for international concern. In 1996, endemic areas included Asia , Africa , and parts of South America . North America , Australia , New Zealand and Japan have been free of FMD for many years. Most European countries have been recognized as free, and countries belonging to the European Union have stopped FMD vaccination . Infection with foot-and-mouth disease tends to occur locally, that is, the virus is passed on to susceptible animals through direct contact with infected animals or with contaminated pens or vehicles used to transport livestock. The clothes and skin of animal handlers such as farmers, standing water, and uncooked food scraps and feed supplements containing infected animal products can harbor the virus as well. Cows can also catch FMD from the semen of infected bulls. Control measures include quarantine and destruction of infected livestock, and export bans for meat and other animal products to countries not infected with the disease. Because FMD rarely infects humans but spreads rapidly among animals, it is a much greater threat to the agriculture industry than to human health. Farmers around the world can lose huge amounts of money during a foot-and-mouth epidemic, when large numbers of animals are destroyed and revenues from milk and meat production go down. One of the difficulties in vaccinating against FMD is the huge variation between and even within serotypes. There is no cross-protection between serotypes (meaning that a vaccine for one serotype won't protect against any others) and in addition, two strains within a given serotype may have nucleotide sequences that differ by as much as 30% for a given gene. This means that FMD vaccines must be highly specific to the strain involved. Vaccination only provides temporary immunity that lasts from months to years. Therefore, rich countries maintain a policy of banning imports from all countries, not proven FMD-free by US or EU standards. This is a point of contention. Although this disease is not dangerous to humans and rarely fatal to otherwise healthy animals, it reduces milk and meat production. Outbreaks can be stopped quickly if farmers and transporters are forced to abide by existing rules. Therefore, (besides temporary discomfort to the animals), any outbreak in the rich world should not be much more as a localized, cyclical economic problem. For countries with free roaming wildlife it is nearly impossible to prove that they are entirely free of this disease. If they try they are forced to erect nationwide fences, which destroys wildlife migration. Because detecting and reporting of FMD have enormously improved and sped up, almost all poor countries could now safely create FMD-free export zones. But rich countries refuse to change the rules. In effect, many poor tropical countries have no chance to meet current rules, so they are still today banned from exporting meat, even if many of them are FMD-free. The result is that if drought hits, the poor try to cope by selling their few animals. This quickly saturates regional demand. The export ban then destroys the value of these animals, in effect destroying the most important coping mechanism of several hundreds of millions extremely poor households. The rules around meat exports have been changed many times, always to accommodate changing circumstances in rich countries, usually further reducing meat export chances for poor countries. For that reason, Kanya and many other countries find the rules very unjust. They are however discouraged to file a formal complaint with WTO by diplomats from rich countries. Citrus canker is a disease affecting citrus species that is caused by the bacterium Xanthomonas axonopodis . The infection causes lesions on the leaves, stems, and fruit of citrus trees, including lime, oranges, and grapefruit. While not harmful to humans, canker significantly affects the vitality of citrus trees, causing leaves and fruit to drop prematurely; a fruit infected with canker is safe to eat but too unsightly to be sold. The disease, which is believed to have originated in South East Asia , is extremely persistent when it becomes established in an area, making it necessary for all citrus orchards to be destroyed for the successful eradication of the disease. Australia , Brazil and the United States are currently experiencing canker outbreaks. [ when? ] The disease can be detected in orchards and on fruit by the appearance of lesions. Early detection is critical in quarantine situations. Bacteria are tested for pathogenicity by inoculating multiple citrus species with the bacterium. Simultaneously, other diagnostic tests (antibody detection, fatty-acid profiling, and genetic procedures using PCR ) are conducted to identify the particular canker strain. Citrus canker outbreaks are prevented and managed in a number of ways. In countries that do not have canker, the disease is prevented from entering the country by quarantine measures. In countries with new outbreaks, eradication programs that are started soon after the disease has been discovered have been successful; such programs rely on the destruction of affected orchards. When eradication has been unsuccessful and the disease has become established, management options include replacing susceptible citrus cultivars with resistant cultivars, applying preventive sprays of copper -based bactericides , and destroying infected trees and all surrounding trees within an appropriate radius. The citrus industry is the largest fresh-fruit exporting industry in Australia. Australia has had three outbreaks of citrus canker; all three were successfully eradicated. The disease was found twice during the 1900s in the Northern Territory and was eradicated each time. During the first outbreak in 1912, every citrus tree north of latitude 19° south was destroyed, taking 11 years to eradicate the disease. In 2004, Asiatic citrus canker was detected in an orchard in Emerald , Queensland , and was thought to have occurred from the illegal import of infected citrus plants. The state and federal governments have ordered that all commercial orchards, all non-commercial citrus trees, and all native lime trees ( C. glauca ) in the vicinity of Emerald be destroyed rather than trying to isolate infected trees. The United Nations Food and Agriculture Organization (FAO) defines food security as existing when "all people, at all times, have physical and economic access to sufficient safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life". The four qualifications that must be met for a food secure system include physical availability, economic and physical access, appropriate utilization, and stability of the prior three elements over time. Of the 6.7 billion people on the planet, about 2 billion are food insecure. As the global population grows to 9 billion by 2050, and as diets shift to emphasize higher energy products and greater overall consumption, food systems will be subjected to even greater pressure. Climate change presents additional threats to food security, affecting crop yields, distribution of pests and diseases, weather patterns, and growing seasons around the world. Food security has thus become an increasingly important topic in agricultural policy as decision makers attempt to reduce poverty and malnutrition while augmenting adaptive capacity to climate change. The Commission on Sustainable Agriculture and Climate Change listed high-priority policy actions to address food security, including integrating food security and sustainable agriculture into global and national policies, significantly raising the level of global investment in food systems, and developing specific programs and policies to support the most vulnerable populations (namely, those that are already subject to food insecurity). ' Food sovereignty ', a term coined by members of Via Campesina in 1996, is about the right of peoples to define their own food systems. Advocates of food sovereignty put the people who produce, distribute, and consume food at the centre of decisions on food systems and policies, rather than the demands of markets and corporations that they believe have come to dominate the global food system. This movement is advocated by a number of farmers, peasants, pastoralists, fisherfolk, indigenous peoples, women, rural youth, and environmental organizations.Policymakers working in poverty reduction in the agriculture sector assess, plan, or enact policies aimed to address the needs of persons living in poverty. Agriculture has been a critical driver of poverty reduction in most developing countries, particularly in rural areas. Approximately 80% of the world's impoverished population, who primarily reside in rural areas and earn their livelihood through farming, can benefit from agriculture in terms of poverty reduction, income generation, and food security. Fostering agricultural development is therefore a crucial element of agricultural policy in a developing country . In addition, a recent Natural Resource Perspective paper by the Overseas Development Institute found that good infrastructure , education and effective information services in rural areas were necessary to improve the chances of making agriculture work for the poor. During the 1980s and 1990s, there was a disregard for the agriculture sector among policymakers and investors, only regaining interest when the prices of staple food crops experienced a significant increase in the mid-2000s. As a result of agricultural policy neglect, there has been a scarcity of investment in infrastructure, which has hindered agricultural development and public goods, such as education, research and development and technology. Rural productive sectors and small agricultural enterprises suffer from market failures due to policies favouring urban areas and lending policies biased against small-scale agricultural firms. Neglect in implementing agriculture policy has been detected in several developing countries. In Indonesia, since the Asian Financial Crisis of 1997 to 1998, the government's agricultural policy has been closely concentrated on achieving price stability and self-sufficiency for import-competing commodities, such as palm oil, sugar and rice. International agencies such as the Food and Agriculture Organization (FAO), the World Bank , the International Fund for Agricultural Development (IFAD) and the Organisation for Economic Co-operation and Development (OECD), espouse the prioritisation of agricultural endeavours to support poverty reduction. The impact of agricultural policy on reducing poverty differs across countries and is influenced by a variety of factors, such as the level of government policy support, the degree of public and private investment in agriculture, the different types of agriculture, and the growth rates of agriculture parallel to non-agriculture sectors. In particular, investment in agricultural research and development has been shown to be highly influential on agricultural GDP growth and poverty reduction. Government policies play a key role in promoting agricultural activities, such as irrigation systems, roads and telecommunication systems, land reform, power in rural areas, fiscal support for research and development, pricing policies, assistance for new technologies, and markets for agricultural produce. Agricultural policies have contributed to meeting the goals related to increasing, diversifying, and improving agricultural production. Agricultural policies aimed at reducing poverty include India's Pradhan Mantri Fasal Bima Yojana , which offers crop insurance to farmers to protect them from weather-related uncertainties and potential crop failures. [ citation needed ] This initiative provides farmers with financial aid for crop loss, reducing the risk of falling into poverty. Rwanda's Crop Intensification Program is another example of such policy, which provides farmers with inputs like fertilisers, improved seeds, and pesticides, as well as training and technical support to help them adopt more efficient farming practices. However, for agricultural policies to contribute to poverty reduction, it is essential that they collaborate effectively and cohesively with other sectors, such as tourism, sustainable economy, and industry. The biosecurity concerns facing industrial agriculture can be illustrated by: the threat to poultry and humans from H5N1 ; possibly caused by the use of animal vaccines the threat to cattle and humans from bovine spongiform encephalopathy (BSE); possibly caused by the unnatural feeding of cattle to cattle to minimize costs the threat to industry profits from diseases like foot-and-mouth disease and citrus canker which increasing globalization makes harder to contain The use of animal vaccines can create new viruses that kill people and cause flu pandemic threats. H5N1 is an example of where this might have already occurred. According to the CDC article "H5N1 Outbreaks and Enzootic Influenza" by Robert G. Webster et al.: "Transmission of highly pathogenic H5N1 from domestic poultry back to migratory waterfowl in western China has increased the geographic spread. The spread of H5N1 and its likely reintroduction to domestic poultry increase the need for good agricultural vaccines. In fact, the root cause of the continuing H5N1 pandemic threat may be the way the pathogenicity of H5N1 viruses is masked by co-circulating influenza viruses or bad agricultural vaccines." Robert Webster explains: "If you use a good vaccine you can prevent the transmission within poultry and to humans. But if they have been using vaccines now [in China] for several years, why is there so much bird flu? There is bad vaccine that stops the disease in the bird but the bird goes on pooping out the virus and maintaining it and changing it. And I think this is what is going on in China. It has to be. Either there is not enough vaccine being used or there is substandard vaccine being used. Probably both. It's not just China. We can't blame China for substandard vaccines. I think there are substandard vaccines for influenza in poultry all over the world." In response to the same concerns, Reuters reports Hong Kong infectious disease expert Lo Wing-lok indicating that vaccines have to take top priority. Julie Hall, who is in charge of the WHO's outbreak response in China, claimed that China's vaccinations might be masking the virus. The BBC reported that Wendy Barclay, a virologist at the University of Reading, UK said: "The Chinese have made a vaccine based on reverse genetics made with H5N1 antigens, and they have been using it. There has been a lot of criticism of what they have done because they have protected their chickens against death from this virus but the chickens still get infected, and then you get the drift - the virus mutates in response to the antibodies - and now we have a situation where we have five or six 'flavours' of H5N1 out there." Bovine spongiform encephalopathy (BSE), commonly known as "mad cow disease", is a fatal, neurodegenerative disease of cattle , which infects by a mechanism that surprised biologists upon its discovery in the late 20th century. In the UK, the country worst affected, 179,000 cattle were infected and 4.4 million were killed as a precaution. The disease can be transmitted to human beings who eat or inhale material from infected carcasses. [ citation needed ] In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease's long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. A British inquiry into BSE concluded that the epidemic was caused by feeding cattle, who are normally herbivores , the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. The infectious agent is distinctive for the high temperatures it is able to survive; this contributed to the spread of the disease in Britain, which had reduced the temperatures used during its rendering process. Another contributory factor was the feeding of infected protein supplements to very young calves instead of milk from their mothers. Foot-and-mouth disease is a highly contagious and sometimes fatal viral disease of cattle and pigs . It can also infect deer , goats , sheep , and other bovids with cloven hooves , as well as elephants , rats , and hedgehogs . Humans are affected only very rarely. FMD occurs throughout much of the world, and while some countries have been free of FMD for some time, its wide host range and rapid spread represent cause for international concern. In 1996, endemic areas included Asia , Africa , and parts of South America . North America , Australia , New Zealand and Japan have been free of FMD for many years. Most European countries have been recognized as free, and countries belonging to the European Union have stopped FMD vaccination . Infection with foot-and-mouth disease tends to occur locally, that is, the virus is passed on to susceptible animals through direct contact with infected animals or with contaminated pens or vehicles used to transport livestock. The clothes and skin of animal handlers such as farmers, standing water, and uncooked food scraps and feed supplements containing infected animal products can harbor the virus as well. Cows can also catch FMD from the semen of infected bulls. Control measures include quarantine and destruction of infected livestock, and export bans for meat and other animal products to countries not infected with the disease. Because FMD rarely infects humans but spreads rapidly among animals, it is a much greater threat to the agriculture industry than to human health. Farmers around the world can lose huge amounts of money during a foot-and-mouth epidemic, when large numbers of animals are destroyed and revenues from milk and meat production go down. One of the difficulties in vaccinating against FMD is the huge variation between and even within serotypes. There is no cross-protection between serotypes (meaning that a vaccine for one serotype won't protect against any others) and in addition, two strains within a given serotype may have nucleotide sequences that differ by as much as 30% for a given gene. This means that FMD vaccines must be highly specific to the strain involved. Vaccination only provides temporary immunity that lasts from months to years. Therefore, rich countries maintain a policy of banning imports from all countries, not proven FMD-free by US or EU standards. This is a point of contention. Although this disease is not dangerous to humans and rarely fatal to otherwise healthy animals, it reduces milk and meat production. Outbreaks can be stopped quickly if farmers and transporters are forced to abide by existing rules. Therefore, (besides temporary discomfort to the animals), any outbreak in the rich world should not be much more as a localized, cyclical economic problem. For countries with free roaming wildlife it is nearly impossible to prove that they are entirely free of this disease. If they try they are forced to erect nationwide fences, which destroys wildlife migration. Because detecting and reporting of FMD have enormously improved and sped up, almost all poor countries could now safely create FMD-free export zones. But rich countries refuse to change the rules. In effect, many poor tropical countries have no chance to meet current rules, so they are still today banned from exporting meat, even if many of them are FMD-free. The result is that if drought hits, the poor try to cope by selling their few animals. This quickly saturates regional demand. The export ban then destroys the value of these animals, in effect destroying the most important coping mechanism of several hundreds of millions extremely poor households. The rules around meat exports have been changed many times, always to accommodate changing circumstances in rich countries, usually further reducing meat export chances for poor countries. For that reason, Kanya and many other countries find the rules very unjust. They are however discouraged to file a formal complaint with WTO by diplomats from rich countries. Citrus canker is a disease affecting citrus species that is caused by the bacterium Xanthomonas axonopodis . The infection causes lesions on the leaves, stems, and fruit of citrus trees, including lime, oranges, and grapefruit. While not harmful to humans, canker significantly affects the vitality of citrus trees, causing leaves and fruit to drop prematurely; a fruit infected with canker is safe to eat but too unsightly to be sold. The disease, which is believed to have originated in South East Asia , is extremely persistent when it becomes established in an area, making it necessary for all citrus orchards to be destroyed for the successful eradication of the disease. Australia , Brazil and the United States are currently experiencing canker outbreaks. [ when? ] The disease can be detected in orchards and on fruit by the appearance of lesions. Early detection is critical in quarantine situations. Bacteria are tested for pathogenicity by inoculating multiple citrus species with the bacterium. Simultaneously, other diagnostic tests (antibody detection, fatty-acid profiling, and genetic procedures using PCR ) are conducted to identify the particular canker strain. Citrus canker outbreaks are prevented and managed in a number of ways. In countries that do not have canker, the disease is prevented from entering the country by quarantine measures. In countries with new outbreaks, eradication programs that are started soon after the disease has been discovered have been successful; such programs rely on the destruction of affected orchards. When eradication has been unsuccessful and the disease has become established, management options include replacing susceptible citrus cultivars with resistant cultivars, applying preventive sprays of copper -based bactericides , and destroying infected trees and all surrounding trees within an appropriate radius. The citrus industry is the largest fresh-fruit exporting industry in Australia. Australia has had three outbreaks of citrus canker; all three were successfully eradicated. The disease was found twice during the 1900s in the Northern Territory and was eradicated each time. During the first outbreak in 1912, every citrus tree north of latitude 19° south was destroyed, taking 11 years to eradicate the disease. In 2004, Asiatic citrus canker was detected in an orchard in Emerald , Queensland , and was thought to have occurred from the illegal import of infected citrus plants. The state and federal governments have ordered that all commercial orchards, all non-commercial citrus trees, and all native lime trees ( C. glauca ) in the vicinity of Emerald be destroyed rather than trying to isolate infected trees.The use of animal vaccines can create new viruses that kill people and cause flu pandemic threats. H5N1 is an example of where this might have already occurred. According to the CDC article "H5N1 Outbreaks and Enzootic Influenza" by Robert G. Webster et al.: "Transmission of highly pathogenic H5N1 from domestic poultry back to migratory waterfowl in western China has increased the geographic spread. The spread of H5N1 and its likely reintroduction to domestic poultry increase the need for good agricultural vaccines. In fact, the root cause of the continuing H5N1 pandemic threat may be the way the pathogenicity of H5N1 viruses is masked by co-circulating influenza viruses or bad agricultural vaccines." Robert Webster explains: "If you use a good vaccine you can prevent the transmission within poultry and to humans. But if they have been using vaccines now [in China] for several years, why is there so much bird flu? There is bad vaccine that stops the disease in the bird but the bird goes on pooping out the virus and maintaining it and changing it. And I think this is what is going on in China. It has to be. Either there is not enough vaccine being used or there is substandard vaccine being used. Probably both. It's not just China. We can't blame China for substandard vaccines. I think there are substandard vaccines for influenza in poultry all over the world." In response to the same concerns, Reuters reports Hong Kong infectious disease expert Lo Wing-lok indicating that vaccines have to take top priority. Julie Hall, who is in charge of the WHO's outbreak response in China, claimed that China's vaccinations might be masking the virus. The BBC reported that Wendy Barclay, a virologist at the University of Reading, UK said: "The Chinese have made a vaccine based on reverse genetics made with H5N1 antigens, and they have been using it. There has been a lot of criticism of what they have done because they have protected their chickens against death from this virus but the chickens still get infected, and then you get the drift - the virus mutates in response to the antibodies - and now we have a situation where we have five or six 'flavours' of H5N1 out there." Bovine spongiform encephalopathy (BSE), commonly known as "mad cow disease", is a fatal, neurodegenerative disease of cattle , which infects by a mechanism that surprised biologists upon its discovery in the late 20th century. In the UK, the country worst affected, 179,000 cattle were infected and 4.4 million were killed as a precaution. The disease can be transmitted to human beings who eat or inhale material from infected carcasses. [ citation needed ] In humans, it is known as new variant Creutzfeldt–Jakob disease (vCJD or nvCJD), and by June 2007, it had killed 165 people in Britain, and six elsewhere with the number expected to rise because of the disease's long incubation period. Between 460,000 and 482,000 BSE-infected animals had entered the human food chain before controls on high-risk offal were introduced in 1989. A British inquiry into BSE concluded that the epidemic was caused by feeding cattle, who are normally herbivores , the remains of other cattle in the form of meat and bone meal (MBM), which caused the infectious agent to spread. The origin of the disease itself remains unknown. The current scientific view is that infectious proteins called prions developed through spontaneous mutation, probably in the 1970s, and there is a possibility that the use of organophosphorus pesticides increased the susceptibility of cattle to the disease. The infectious agent is distinctive for the high temperatures it is able to survive; this contributed to the spread of the disease in Britain, which had reduced the temperatures used during its rendering process. Another contributory factor was the feeding of infected protein supplements to very young calves instead of milk from their mothers. Foot-and-mouth disease is a highly contagious and sometimes fatal viral disease of cattle and pigs . It can also infect deer , goats , sheep , and other bovids with cloven hooves , as well as elephants , rats , and hedgehogs . Humans are affected only very rarely. FMD occurs throughout much of the world, and while some countries have been free of FMD for some time, its wide host range and rapid spread represent cause for international concern. In 1996, endemic areas included Asia , Africa , and parts of South America . North America , Australia , New Zealand and Japan have been free of FMD for many years. Most European countries have been recognized as free, and countries belonging to the European Union have stopped FMD vaccination . Infection with foot-and-mouth disease tends to occur locally, that is, the virus is passed on to susceptible animals through direct contact with infected animals or with contaminated pens or vehicles used to transport livestock. The clothes and skin of animal handlers such as farmers, standing water, and uncooked food scraps and feed supplements containing infected animal products can harbor the virus as well. Cows can also catch FMD from the semen of infected bulls. Control measures include quarantine and destruction of infected livestock, and export bans for meat and other animal products to countries not infected with the disease. Because FMD rarely infects humans but spreads rapidly among animals, it is a much greater threat to the agriculture industry than to human health. Farmers around the world can lose huge amounts of money during a foot-and-mouth epidemic, when large numbers of animals are destroyed and revenues from milk and meat production go down. One of the difficulties in vaccinating against FMD is the huge variation between and even within serotypes. There is no cross-protection between serotypes (meaning that a vaccine for one serotype won't protect against any others) and in addition, two strains within a given serotype may have nucleotide sequences that differ by as much as 30% for a given gene. This means that FMD vaccines must be highly specific to the strain involved. Vaccination only provides temporary immunity that lasts from months to years. Therefore, rich countries maintain a policy of banning imports from all countries, not proven FMD-free by US or EU standards. This is a point of contention. Although this disease is not dangerous to humans and rarely fatal to otherwise healthy animals, it reduces milk and meat production. Outbreaks can be stopped quickly if farmers and transporters are forced to abide by existing rules. Therefore, (besides temporary discomfort to the animals), any outbreak in the rich world should not be much more as a localized, cyclical economic problem. For countries with free roaming wildlife it is nearly impossible to prove that they are entirely free of this disease. If they try they are forced to erect nationwide fences, which destroys wildlife migration. Because detecting and reporting of FMD have enormously improved and sped up, almost all poor countries could now safely create FMD-free export zones. But rich countries refuse to change the rules. In effect, many poor tropical countries have no chance to meet current rules, so they are still today banned from exporting meat, even if many of them are FMD-free. The result is that if drought hits, the poor try to cope by selling their few animals. This quickly saturates regional demand. The export ban then destroys the value of these animals, in effect destroying the most important coping mechanism of several hundreds of millions extremely poor households. The rules around meat exports have been changed many times, always to accommodate changing circumstances in rich countries, usually further reducing meat export chances for poor countries. For that reason, Kanya and many other countries find the rules very unjust. They are however discouraged to file a formal complaint with WTO by diplomats from rich countries.Citrus canker is a disease affecting citrus species that is caused by the bacterium Xanthomonas axonopodis . The infection causes lesions on the leaves, stems, and fruit of citrus trees, including lime, oranges, and grapefruit. While not harmful to humans, canker significantly affects the vitality of citrus trees, causing leaves and fruit to drop prematurely; a fruit infected with canker is safe to eat but too unsightly to be sold. The disease, which is believed to have originated in South East Asia , is extremely persistent when it becomes established in an area, making it necessary for all citrus orchards to be destroyed for the successful eradication of the disease. Australia , Brazil and the United States are currently experiencing canker outbreaks. [ when? ] The disease can be detected in orchards and on fruit by the appearance of lesions. Early detection is critical in quarantine situations. Bacteria are tested for pathogenicity by inoculating multiple citrus species with the bacterium. Simultaneously, other diagnostic tests (antibody detection, fatty-acid profiling, and genetic procedures using PCR ) are conducted to identify the particular canker strain. Citrus canker outbreaks are prevented and managed in a number of ways. In countries that do not have canker, the disease is prevented from entering the country by quarantine measures. In countries with new outbreaks, eradication programs that are started soon after the disease has been discovered have been successful; such programs rely on the destruction of affected orchards. When eradication has been unsuccessful and the disease has become established, management options include replacing susceptible citrus cultivars with resistant cultivars, applying preventive sprays of copper -based bactericides , and destroying infected trees and all surrounding trees within an appropriate radius. The citrus industry is the largest fresh-fruit exporting industry in Australia. Australia has had three outbreaks of citrus canker; all three were successfully eradicated. The disease was found twice during the 1900s in the Northern Territory and was eradicated each time. During the first outbreak in 1912, every citrus tree north of latitude 19° south was destroyed, taking 11 years to eradicate the disease. In 2004, Asiatic citrus canker was detected in an orchard in Emerald , Queensland , and was thought to have occurred from the illegal import of infected citrus plants. The state and federal governments have ordered that all commercial orchards, all non-commercial citrus trees, and all native lime trees ( C. glauca ) in the vicinity of Emerald be destroyed rather than trying to isolate infected trees.The United Nations Food and Agriculture Organization (FAO) defines food security as existing when "all people, at all times, have physical and economic access to sufficient safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life". The four qualifications that must be met for a food secure system include physical availability, economic and physical access, appropriate utilization, and stability of the prior three elements over time. Of the 6.7 billion people on the planet, about 2 billion are food insecure. As the global population grows to 9 billion by 2050, and as diets shift to emphasize higher energy products and greater overall consumption, food systems will be subjected to even greater pressure. Climate change presents additional threats to food security, affecting crop yields, distribution of pests and diseases, weather patterns, and growing seasons around the world. Food security has thus become an increasingly important topic in agricultural policy as decision makers attempt to reduce poverty and malnutrition while augmenting adaptive capacity to climate change. The Commission on Sustainable Agriculture and Climate Change listed high-priority policy actions to address food security, including integrating food security and sustainable agriculture into global and national policies, significantly raising the level of global investment in food systems, and developing specific programs and policies to support the most vulnerable populations (namely, those that are already subject to food insecurity). ' Food sovereignty ', a term coined by members of Via Campesina in 1996, is about the right of peoples to define their own food systems. Advocates of food sovereignty put the people who produce, distribute, and consume food at the centre of decisions on food systems and policies, rather than the demands of markets and corporations that they believe have come to dominate the global food system. This movement is advocated by a number of farmers, peasants, pastoralists, fisherfolk, indigenous peoples, women, rural youth, and environmental organizations.An agricultural subsidy is a governmental subsidy paid to farmers and agribusinesses to manage the agricultural industry as one part of the various methods a government uses in a mixed economy . The conditions for payment and the reasons for the individual specific subsidies vary with farm product, size of the farm, nature of ownership, and country among other factors. Enriching peanut farmers for political purposes, keeping the price of a staple low to keep the poor from rebelling, stabilizing the production of a crop to avoid famine years, encouraging diversification and many other purposes have been suggested as the reason for specific subsidies. Price floors or price ceilings set a minimum or maximum price for a product. Price controls encourage more production by a price floor or less production by a price ceiling. A government can erect trade barriers to limit the number of goods imported (in the case of a Quota Share) or enact tariffs to raise the domestic price of imported products. These barriers give preference to domestic producers.Some argue that nations have an interest in assuring there is sufficient domestic production capability to meet domestic needs in the event of a global supply disruption. Significant dependence on foreign food producers makes a country strategically vulnerable in the event of war, blockade or embargo. Maintaining adequate domestic capability allows for food self-sufficiency that lessens the risk of supply shocks due to geopolitical events. Agricultural policies may be used to support domestic producers as they gain domestic and international market share. This may be a short term way of encouraging an industry until it is large enough to thrive without aid. Or it may be an ongoing subsidy designed to allow a product to compete with or undercut the foreign competition. This may produce a net gain for a government despite the cost of interventions because it allows a country to build up an export industry or reduce imports. It also helps to form the nation's supply and demand market. Farm or undeveloped land composes the majority of land in most countries. Policies may encourage some land uses rather than others in the interest of protecting the environment. For instance, subsidies may be given for particular farming methods, forestation, land clearance, or pollution abatement. Subsidising farming may encourage people to remain on the land and obtain some income. This might be relevant to an agrarian country with many peasant farmers, but it may also be a consideration to more developed countries such as Poland . It has a very high unemployment rate, much farmland and retains a large rural population growing food for their own use. Price controls may also be used to assist poor citizens. Many countries have used this method of welfare support as it delivers cheap food to the poorest in urban areas without the need to assess people to give them financial aid. This often goes at the cost of the rural poor, who then earn less from what is often their only realistic or potential source of income: agriculture. Because in almost all countries the rural poor are poorer than the urban poor, cheap food policies through price controls often increase overall poverty. The same often counts for poverty relief in the form of food aid, which (unless while during severe drought) drives small producers in poor countries out of production. It tends to benefit lower middle class groups (sub-urban and urban poor) at the expense of the poorest 20 percent, who as a result remain deprived of customers. Welfare economics theory holds that sometimes private activities can impose social costs upon others. Industrial agriculture is widely considered to impose social costs through pesticide pollution and nitrate pollution . Further, agriculture uses large amounts of water, a scarce resource . Some economists argue that taxes should be levied on agriculture, or that organic agriculture, which uses little pesticides and experiences relatively little nitrate runoff, should be encouraged with subsidies. In the United States, 65% of the approximately $16.5 billion in annual subsidies went to the top 10% of farmers in 2002 because subsidies are linked to certain commodities. On the other hand, organic farming received $5 million for help in certification and $15 million for research over a 5-year time period. Some advocate Fair Trade rules to ensure that poor farmers in developing nations that produce crops primarily for export are not exploited or negatively impacted by trade policies, practices, tariffs, and agreements which benefit one competitor at the expense of another - which advocates consider a dangerous "race to the bottom" in agricultural labor and safety standards. Opponents point out that most agriculture in developed nations is produced by industrial corporations (agribusiness) which are hardly deserving of sympathy, and that the alternative to exploitation is poverty. [ citation needed ] Fair trade steak? Much of what developing countries export to the rich world, also comes from industrial corporations. The reason for that is, that rich countries have put up elaborate quality demands, most of whom make no factual health contribution. [ citation needed ] Small farmers often in effect meet these demands, but are rarely able to prove that in western standards. [ citation needed ] Therefore, the biggest impediment to the growth of small farming and therefore of fair trade in sectors beyond coffee and bananas, is these quality demands from the rich world. [ citation needed ]Some argue that nations have an interest in assuring there is sufficient domestic production capability to meet domestic needs in the event of a global supply disruption. Significant dependence on foreign food producers makes a country strategically vulnerable in the event of war, blockade or embargo. Maintaining adequate domestic capability allows for food self-sufficiency that lessens the risk of supply shocks due to geopolitical events. Agricultural policies may be used to support domestic producers as they gain domestic and international market share. This may be a short term way of encouraging an industry until it is large enough to thrive without aid. Or it may be an ongoing subsidy designed to allow a product to compete with or undercut the foreign competition. This may produce a net gain for a government despite the cost of interventions because it allows a country to build up an export industry or reduce imports. It also helps to form the nation's supply and demand market.Farm or undeveloped land composes the majority of land in most countries. Policies may encourage some land uses rather than others in the interest of protecting the environment. For instance, subsidies may be given for particular farming methods, forestation, land clearance, or pollution abatement.Subsidising farming may encourage people to remain on the land and obtain some income. This might be relevant to an agrarian country with many peasant farmers, but it may also be a consideration to more developed countries such as Poland . It has a very high unemployment rate, much farmland and retains a large rural population growing food for their own use. Price controls may also be used to assist poor citizens. Many countries have used this method of welfare support as it delivers cheap food to the poorest in urban areas without the need to assess people to give them financial aid. This often goes at the cost of the rural poor, who then earn less from what is often their only realistic or potential source of income: agriculture. Because in almost all countries the rural poor are poorer than the urban poor, cheap food policies through price controls often increase overall poverty. The same often counts for poverty relief in the form of food aid, which (unless while during severe drought) drives small producers in poor countries out of production. It tends to benefit lower middle class groups (sub-urban and urban poor) at the expense of the poorest 20 percent, who as a result remain deprived of customers.Welfare economics theory holds that sometimes private activities can impose social costs upon others. Industrial agriculture is widely considered to impose social costs through pesticide pollution and nitrate pollution . Further, agriculture uses large amounts of water, a scarce resource . Some economists argue that taxes should be levied on agriculture, or that organic agriculture, which uses little pesticides and experiences relatively little nitrate runoff, should be encouraged with subsidies. In the United States, 65% of the approximately $16.5 billion in annual subsidies went to the top 10% of farmers in 2002 because subsidies are linked to certain commodities. On the other hand, organic farming received $5 million for help in certification and $15 million for research over a 5-year time period.Some advocate Fair Trade rules to ensure that poor farmers in developing nations that produce crops primarily for export are not exploited or negatively impacted by trade policies, practices, tariffs, and agreements which benefit one competitor at the expense of another - which advocates consider a dangerous "race to the bottom" in agricultural labor and safety standards. Opponents point out that most agriculture in developed nations is produced by industrial corporations (agribusiness) which are hardly deserving of sympathy, and that the alternative to exploitation is poverty. [ citation needed ] Fair trade steak? Much of what developing countries export to the rich world, also comes from industrial corporations. The reason for that is, that rich countries have put up elaborate quality demands, most of whom make no factual health contribution. [ citation needed ] Small farmers often in effect meet these demands, but are rarely able to prove that in western standards. [ citation needed ] Therefore, the biggest impediment to the growth of small farming and therefore of fair trade in sectors beyond coffee and bananas, is these quality demands from the rich world. [ citation needed ]In international trade parlance, when a company from country A sells a commodity below the cost of production into country B, this is called " dumping ". A number of countries that are signatories to multilateral trade agreements have provisions that prohibit this practice. When rich countries subsidize domestic production, the excess output is often given to the developing world as foreign aid. This process eliminates the domestic market for agricultural products in the developing world because the products can be obtained for free from western aid agencies. In developing nations where these effects are most severe, small farmers could no longer afford basic inputs and were forced to sell their land. "Consider a farmer in Ghana who used to be able to make a living growing rice. Several years ago, Ghana was able to feed and export their surplus. Now, it imports rice. From where? Developed countries. Why? Because it's cheaper. Even if it costs the rice producer in the developed world much more to produce the rice, he doesn't have to make a profit from his crop. The government pays him to grow it, so he can sell it more cheaply to Ghana than the farmer in Ghana can. And that farmer in Ghana? He can't feed his family anymore." ( Lyle Vanclief , former Canadian Minister of Agriculture [1997-2003]) According to the Institute for Agriculture and Trade Policy , corn, soybeans, cotton, wheat and rice are sold below the cost of production, or dumped. Dumping rates are approximately forty percent for wheat, between twenty-five and thirty percent for corn (maize), approximately thirty percent for soybeans, fifty-seven percent for cotton, and approximately twenty percent for rice. For example, wheat is sold for forty percent below cost. According to Oxfam, "If developed nations eliminated subsidy programs, the export value of agriculture in lesser developed nations would increase by 24 %, plus a further 5.5 % from tariff equilibrium. ... exporters can offer US surpluses for sale at prices around half the cost of production; destroying local agriculture and creating a captive market in the process." Free trade advocates desire the elimination of all market distorting mechanisms (subsidies, tariffs, regulations) and argue that, as with free trade in all areas, this will result in aggregate benefit for all. This position is particularly popular in competitive agricultural exporting nations in both the developed and developing world, some of whom have banded together in the Cairns Group lobby. Canada's Department of Agriculture estimates that developing nations would benefit by about $4 billion annually if subsidies in the developed world were halved. Many developing countries do not grow enough food to feed their own populations. These nations must buy food from other countries. Lower prices and free food save the lives of millions of starving people, despite the drop in food sales of the local farmers. A developing nation could use new improved farming methods to grow more food, with the ultimate goal of feeding their nation without outside help. New greenhouse methods, hydroponics, fertilizers, R/O water processors, hybrid crops, fast-growing hybrid trees for quick shade, interior temperature control, greenhouse or tent insulation, autonomous building gardens, sun lamps, mylar, fans, and other cheap tech can be used to grow crops on previously un arable land , such as rocky, mountainous, desert, and even Arctic lands. More food can be grown, reducing dependency on other countries for food. Replacement crops can also make nations agriculturally independent. Sugar, for example, comes from sugar cane imported from Polynesia . Instead of buying the sugar from Polynesia , a nation can make sugar from sugar beets, maple sap, or sweetener from stevia plant, keeping the profits circulating within the nation's economy. Paper and clothes can be made of hemp instead of trees and cotton. Tropical foods won't grow in many places in Europe, but they will grow in insulated greenhouses or tents in Europe. Soybean plant cellulose can replace plastic (made from oil). Ethanol from farm waste or hempseed oil can replace gasoline. Rainforest medicine plants grown locally can replace many imported medicines. Alternates of cash crops, like sugar and oil replacements, can reduce farmers' dependency on subsidies in both developed and developing nations. Market interventions may increase the cost to consumers for agricultural products, either via hidden wealth-transfers via the government, or increased prices at the consumer level, such as for sugar and peanuts in the US. This has led to market distortions , such as food processors using high fructose corn syrup as a replacement for sugar. High fructose corn syrup may be an unhealthy food additive, and, were sugar prices not inflated by government fiat, sugar might be preferred over high fructose corn syrup in the marketplace.In international trade parlance, when a company from country A sells a commodity below the cost of production into country B, this is called " dumping ". A number of countries that are signatories to multilateral trade agreements have provisions that prohibit this practice. When rich countries subsidize domestic production, the excess output is often given to the developing world as foreign aid. This process eliminates the domestic market for agricultural products in the developing world because the products can be obtained for free from western aid agencies. In developing nations where these effects are most severe, small farmers could no longer afford basic inputs and were forced to sell their land. "Consider a farmer in Ghana who used to be able to make a living growing rice. Several years ago, Ghana was able to feed and export their surplus. Now, it imports rice. From where? Developed countries. Why? Because it's cheaper. Even if it costs the rice producer in the developed world much more to produce the rice, he doesn't have to make a profit from his crop. The government pays him to grow it, so he can sell it more cheaply to Ghana than the farmer in Ghana can. And that farmer in Ghana? He can't feed his family anymore." ( Lyle Vanclief , former Canadian Minister of Agriculture [1997-2003]) According to the Institute for Agriculture and Trade Policy , corn, soybeans, cotton, wheat and rice are sold below the cost of production, or dumped. Dumping rates are approximately forty percent for wheat, between twenty-five and thirty percent for corn (maize), approximately thirty percent for soybeans, fifty-seven percent for cotton, and approximately twenty percent for rice. For example, wheat is sold for forty percent below cost. According to Oxfam, "If developed nations eliminated subsidy programs, the export value of agriculture in lesser developed nations would increase by 24 %, plus a further 5.5 % from tariff equilibrium. ... exporters can offer US surpluses for sale at prices around half the cost of production; destroying local agriculture and creating a captive market in the process." Free trade advocates desire the elimination of all market distorting mechanisms (subsidies, tariffs, regulations) and argue that, as with free trade in all areas, this will result in aggregate benefit for all. This position is particularly popular in competitive agricultural exporting nations in both the developed and developing world, some of whom have banded together in the Cairns Group lobby. Canada's Department of Agriculture estimates that developing nations would benefit by about $4 billion annually if subsidies in the developed world were halved.Many developing countries do not grow enough food to feed their own populations. These nations must buy food from other countries. Lower prices and free food save the lives of millions of starving people, despite the drop in food sales of the local farmers. A developing nation could use new improved farming methods to grow more food, with the ultimate goal of feeding their nation without outside help. New greenhouse methods, hydroponics, fertilizers, R/O water processors, hybrid crops, fast-growing hybrid trees for quick shade, interior temperature control, greenhouse or tent insulation, autonomous building gardens, sun lamps, mylar, fans, and other cheap tech can be used to grow crops on previously un arable land , such as rocky, mountainous, desert, and even Arctic lands. More food can be grown, reducing dependency on other countries for food. Replacement crops can also make nations agriculturally independent. Sugar, for example, comes from sugar cane imported from Polynesia . Instead of buying the sugar from Polynesia , a nation can make sugar from sugar beets, maple sap, or sweetener from stevia plant, keeping the profits circulating within the nation's economy. Paper and clothes can be made of hemp instead of trees and cotton. Tropical foods won't grow in many places in Europe, but they will grow in insulated greenhouses or tents in Europe. Soybean plant cellulose can replace plastic (made from oil). Ethanol from farm waste or hempseed oil can replace gasoline. Rainforest medicine plants grown locally can replace many imported medicines. Alternates of cash crops, like sugar and oil replacements, can reduce farmers' dependency on subsidies in both developed and developing nations. Market interventions may increase the cost to consumers for agricultural products, either via hidden wealth-transfers via the government, or increased prices at the consumer level, such as for sugar and peanuts in the US. This has led to market distortions , such as food processors using high fructose corn syrup as a replacement for sugar. High fructose corn syrup may be an unhealthy food additive, and, were sugar prices not inflated by government fiat, sugar might be preferred over high fructose corn syrup in the marketplace.The concerns of agricultural policies are extensive, and includes ensuring the hygiene of salads, globalization management, and other emerging issues. The majority of the concerns fall into three categories: food supply for a growing population, livelihood insurance for farmers, and environmental protection. The theme of all approaches aiming to address these 3 types of concerns is to have a holistic view of their effects and externalities [ citation needed ] (a by-product of an action that affects others without their consent), because some policies intended to address one aspect of the concerns may have unintended harmful consequences that worsen other aspects while some have zero or negative beneficial effects. For example, subsidizing agricultural companies allows them to expand their industry and offer their products at lower prices to customers, but increases the firm's water and land usage which are at the cost of natural habitats. From an opposite perspective, if we protect the natural habitats and tax the agricultural firm for turning natural lands into factories, the prices of their products increase, making the firm's products too expensive for some customers. These externalities and trade-offs put the policymakers in a dilemma because our current global agriculture system is vulnerable to many disruptions such as weather changes, locality, manpower shifts, etc. Consequently, before we resolve this primary fragility of our agriculture system. It's of high cruciality for policymakers to weigh the trade-offs and adopt the most appropriate policies. There are examples of the agricultural policy design mentioned above that are made by worldwide unions, countries, and states. While every specific situation requires its own specific agricultural policy design, these examples can provide useful models, insights, and lessons for future policymakers' reference and inspiration. The Common Agricultural Policy , published by E.U., uses government subsidies to encourage food production and farming industrialization in its early stage. [ citation needed ] In some areas, food production boomed so much that enormous food waste became a new problem. With food waste, the market was thrown into imbalance. Consequently, the price drop cost the farmers' utility and has led to a future reform known as the Marsholt Plan. Marsholt Plan and following reforms generally adjusted the agriculture market back to balance. Later reforms managed to spread the fund to farmers and increase each individual farmers' welfare instead of merely expanding croplands and industries. Starting from 2003, the Common Agricultural Policy fund is further detailed into individuals and environmental protection is finally put into consideration. The farmer population is approximately five percent of the total population in the E.U. and 1.7% in the U.S. [ citation needed ] The total value of agricultural production in the E.U. amounted to 128 billion euros (1998). About forty-nine percent of this amount was accounted for by political measures: 37 billion euros due to direct payments and 43 billion euros from consumers due to the artificially high price. Eighty percent of European farmers receive a direct payment of 5,000 euros or less, while 2.2% receive a direct payment above 50,000 euros, totaling forty percent of all direct subsidies. The average U.S. farmer receives $16,000 in annual subsidies. Two-thirds of farmers receive no direct payments. Of those that do, the average amount amongst the lowest paid eighty percent was $7000 from 1995 to 2003. Subsidies are a mix of tax reductions, direct cash payments and below-market prices on water and other inputs. Some claim that these aggregate figures are misleading because large agribusinesses , rather than individual farmers, receive a significant share of total subsidy spending. The Federal Agriculture Improvement and Reform Act of 1996 reduced farm subsidies, providing fixed payments over a period and replacing price supports and subsidies. The Farm Security and Rural Investment Act of 2002 contains direct and countercyclical payments designed to limit the effects of low prices and yields. In the EU, €54 billion of subsidies are paid every year. An increasing share of the subsidies is being decoupled from production and lumped into the Single Farm Payment. While this has diminished the distortions created by the Common Agricultural Policy, many critics argue that a greater focus on the provision of public goods, such as biodiversity and clean water, is needed. The next major reform is expected for 2014 when a new long-term EU budget is coming into effect. The U.S. Conservation Reserve Program leases land from producers that take marginal land out of production and convert it back to a near-natural state by planting native grasses and other plants. The U.S. Environmental Quality Incentives Program subsidizes improvements which promote water conservation and other measures. This program is conducted under a bidding process using a formula where farmers request a certain percentage of cost share for improvement such as drip irrigation. Producers that offer the most environmental improvement based on a point system for the least cost are funded first. The process continues until that year's allocated funds are expended. The concerns of agricultural policies are extensive, and includes ensuring the hygiene of salads, globalization management, and other emerging issues. The majority of the concerns fall into three categories: food supply for a growing population, livelihood insurance for farmers, and environmental protection. The theme of all approaches aiming to address these 3 types of concerns is to have a holistic view of their effects and externalities [ citation needed ] (a by-product of an action that affects others without their consent), because some policies intended to address one aspect of the concerns may have unintended harmful consequences that worsen other aspects while some have zero or negative beneficial effects. For example, subsidizing agricultural companies allows them to expand their industry and offer their products at lower prices to customers, but increases the firm's water and land usage which are at the cost of natural habitats. From an opposite perspective, if we protect the natural habitats and tax the agricultural firm for turning natural lands into factories, the prices of their products increase, making the firm's products too expensive for some customers. These externalities and trade-offs put the policymakers in a dilemma because our current global agriculture system is vulnerable to many disruptions such as weather changes, locality, manpower shifts, etc. Consequently, before we resolve this primary fragility of our agriculture system. It's of high cruciality for policymakers to weigh the trade-offs and adopt the most appropriate policies. There are examples of the agricultural policy design mentioned above that are made by worldwide unions, countries, and states. While every specific situation requires its own specific agricultural policy design, these examples can provide useful models, insights, and lessons for future policymakers' reference and inspiration. The Common Agricultural Policy , published by E.U., uses government subsidies to encourage food production and farming industrialization in its early stage. [ citation needed ] In some areas, food production boomed so much that enormous food waste became a new problem. With food waste, the market was thrown into imbalance. Consequently, the price drop cost the farmers' utility and has led to a future reform known as the Marsholt Plan. Marsholt Plan and following reforms generally adjusted the agriculture market back to balance. Later reforms managed to spread the fund to farmers and increase each individual farmers' welfare instead of merely expanding croplands and industries. Starting from 2003, the Common Agricultural Policy fund is further detailed into individuals and environmental protection is finally put into consideration. The farmer population is approximately five percent of the total population in the E.U. and 1.7% in the U.S. [ citation needed ] The total value of agricultural production in the E.U. amounted to 128 billion euros (1998). About forty-nine percent of this amount was accounted for by political measures: 37 billion euros due to direct payments and 43 billion euros from consumers due to the artificially high price. Eighty percent of European farmers receive a direct payment of 5,000 euros or less, while 2.2% receive a direct payment above 50,000 euros, totaling forty percent of all direct subsidies. The average U.S. farmer receives $16,000 in annual subsidies. Two-thirds of farmers receive no direct payments. Of those that do, the average amount amongst the lowest paid eighty percent was $7000 from 1995 to 2003. Subsidies are a mix of tax reductions, direct cash payments and below-market prices on water and other inputs. Some claim that these aggregate figures are misleading because large agribusinesses , rather than individual farmers, receive a significant share of total subsidy spending. The Federal Agriculture Improvement and Reform Act of 1996 reduced farm subsidies, providing fixed payments over a period and replacing price supports and subsidies. The Farm Security and Rural Investment Act of 2002 contains direct and countercyclical payments designed to limit the effects of low prices and yields. In the EU, €54 billion of subsidies are paid every year. An increasing share of the subsidies is being decoupled from production and lumped into the Single Farm Payment. While this has diminished the distortions created by the Common Agricultural Policy, many critics argue that a greater focus on the provision of public goods, such as biodiversity and clean water, is needed. The next major reform is expected for 2014 when a new long-term EU budget is coming into effect.The U.S. Conservation Reserve Program leases land from producers that take marginal land out of production and convert it back to a near-natural state by planting native grasses and other plants. The U.S. Environmental Quality Incentives Program subsidizes improvements which promote water conservation and other measures. This program is conducted under a bidding process using a formula where farmers request a certain percentage of cost share for improvement such as drip irrigation. Producers that offer the most environmental improvement based on a point system for the least cost are funded first. The process continues until that year's allocated funds are expended. In April 2004 the World Trade Organization (WTO) ruled that 3 billion dollars in US cotton subsidies violate trade agreements and that almost 50% of EU sugar exports are illegal. In 1997–2003, US cotton exports were subsidized by an average of 48%. The WTO has extracted commitments from the Philippines government, making it lower import barriers to half their present levels over a span of six years, and allowing in drastically increased competition from the industrialised and heavily subsidised farming systems of North America and Europe. A recent Oxfam report estimated that average household incomes of maize farmers will be reduced by as much as 30% over the six years as cheap imports from the US drive down prices in the local markets. The report estimates that in the absence of trade restrictions, US subsidised maize could be marketed at less than half the price of maize grown on the Philippine island of Mindanao ; and that the livelihoods of up to half a million Filipino maize farmers (out of the total 1.2 million) are under immediate threat.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/2009_swine_flu_pandemic/html

2009 swine flu pandemic

The 2009 swine flu pandemic , caused by the H1N1/swine flu/influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, was the third recent flu pandemic involving the H1N1 virus (the first being the 1918–1920 Spanish flu pandemic and the second being the 1977 Russian flu ). The first identified human case was in La Gloria , Mexico, a rural town in Veracruz. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term " swine flu ". Some studies estimated that the real number of cases including asymptomatic and mild cases could be 700 million to 1.4 billion people—or 11 to 21 percent of the global population of 6.8 billion at the time. The lower value of 700 million is more than the 500 million people estimated to have been infected by the Spanish flu pandemic. However, the Spanish flu infected approximately a third of the world population at the time, a much higher proportion. The number of lab-confirmed deaths reported to the WHO is 18,449 and is widely considered a gross underestimate. The WHO collaborated with the US Centers for Disease Control and Prevention (USCDC) and Netherlands Institute for Health Services Research (NIVEL) to produce two independent estimates of the influenza deaths that occurred during the global pandemic using two distinct methodologies. The 2009 H1N1 flu pandemic is estimated to have actually caused about 284,000 (range from 150,000 to 575,000) excess deaths by the WHO-USCDC study and 148,000–249,000 excess respiratory deaths by the WHO-NIVEL study. A study done in September 2010 showed that the risk of serious illness resulting from the 2009 H1N1 flu was no higher than that of the yearly seasonal flu . For comparison, the WHO estimates that 250,000 to 500,000 people die of seasonal flu annually. However, the H1N1 influenza epidemic in 2009 resulted in a large increase in the number of new cases of narcolepsy . Unlike most strains of influenza, the pandemic H1N1/09 virus did not disproportionately infect adults older than 60 years; this was an unusual and characteristic feature of the H1N1 pandemic . Even in the case of previously healthy people, a small percentage develop pneumonia or acute respiratory distress syndrome (ARDS). This manifests itself as increased breathing difficulty and typically occurs three to six days after initial onset of flu symptoms. The pneumonia caused by flu can be either direct viral pneumonia or a secondary bacterial pneumonia . A November 2009 New England Journal of Medicine article recommended that flu patients whose chest X-ray indicates pneumonia receive both antivirals and antibiotics . In particular, it is a warning sign if a child seems to be getting better and then relapses with high fever, as this relapse may be bacterial pneumonia. The World Health Organization uses the term "(H1N1) 2009 pandemic" when referring to the event, and officially adopted the name "A(H1N1)pdm09" for the virus in 2010, after the conclusion of the pandemic. Controversy arose early on regarding the wide assortment of terms used by journalists, academics, and officials. Labels like "H1N1 flu", "Swine flu", "Mexican flu", and variations thereof were typical. Criticism centered on how these names may confuse or mislead the public. It was argued that the names were overly technical (e.g. "H1N1"), incorrectly implying that the disease is caused by contact with pigs or pig products, or provoking stigmatization against certain communities (e.g. "Mexican"). Some academics of the time asserted there is nothing wrong with such names, while research published years later (in 2013) concluded that Mexican Americans and Latino Americans had indeed been stigmatized due to the frequent use of term "Mexican flu" in the news media. Official entities adopted terms with varying consistency over the course of the pandemic. The CDC used names like "novel influenza A (H1N1)" or "2009 H1N1 flu". The Netherlands National Institute for Public Health and the Environment used the term "Pig Flu" early on. Officials in Taiwan suggested use of the names "H1N1 flu" or "new flu". The World Organization for Animal Health , an IGO based in Europe, proposed the name "North American influenza". The European Commission adopted the term "novel flu virus". Officials in Israel and South Korea briefly considered adoption of the name "Mexican virus" due to concern about the use of the word "swine". In Israel, objections stemmed from sensitivity to religious restrictions on eating pork in the Jewish and Muslim populations, in South Korea , concerns were influenced by the importance of pork and domestic pigs . As terminology changed to deal with these and other such issues, further criticism was made that the situation was unnecessarily confusing. For example, the news department at the journal Science produced an article with the humorous title "Swine Flu Names Evolving Faster Than Swine Flu Itself". Analysis of the genetic divergence of the virus in samples from different cases indicated that the virus jumped to humans in 2008, probably after June, and not later than the end of November, likely around September 2008. The research also indicated the virus had been latent in pigs for several months prior to the outbreak, suggesting a need to increase agricultural surveillance to prevent future outbreaks. In 2009, U.S. agricultural officials speculated, although emphasizing that there was no way to prove their hypothesis, that "contrary to the popular assumption that the new swine flu pandemic arose on factory farms in Mexico, [the virus] most likely emerged in pigs in Asia, but then traveled to North America in a human." However, a subsequent report by researchers at the Mount Sinai School of Medicine in 2016 found that the 2009 H1N1 virus likely originated from pigs in a very small region of central Mexico. Initially called an "outbreak", widespread H1N1 infection was first recognized in the state of Veracruz , Mexico, with evidence that the virus had been present for months before it was officially called an "epidemic". The Mexican government closed most of Mexico City 's public and private facilities in an attempt to contain the spread of the virus; however, it continued to spread globally, and clinics in some areas were overwhelmed by infected people. The new virus was first isolated in late April by American and Canadian laboratories from samples taken from people with flu in Mexico, Southern California, and Texas. Soon the earliest known human case was traced to a case from 9 March 2009 in a 5-year-old boy in La Gloria, Mexico, a rural town in Veracruz. In late April, the World Health Organization (WHO) declared its first ever "public health emergency of international concern", or PHEIC , and in June, the WHO and the U.S. CDC stopped counting cases and declared the outbreak a pandemic . Despite being informally called "swine flu", the H1N1 flu virus cannot be spread by eating pork products; similar to other influenza viruses, it is typically contracted by person to person transmission through respiratory droplets. Symptoms usually last 4–6 days. Antivirals ( oseltamivir or zanamivir ) were recommended for those with more severe symptoms or those in an at-risk group. The pandemic began to taper off in November 2009, and by May 2010, the number of cases was in steep decline. On 10 August 2010, the Director-General of the WHO, Margaret Chan , announced the end of the H1N1 pandemic and announced that the H1N1 influenza event had moved into the post-pandemic period. According to WHO statistics (as of July 2010), the virus had killed more than 18,000 people since it appeared in April 2009; however, they state that the total mortality (including deaths unconfirmed or unreported) from the H1N1 strain is "unquestionably higher". Critics claimed the WHO had exaggerated the danger, spreading "fear and confusion" rather than "immediate information". The WHO began an investigation to determine whether it had "frightened people unnecessarily". A flu follow-up study done in September 2010, found that "the risk of most serious complications was not elevated in adults or children." In a 5 August 2011 PLOS ONE article, researchers estimated that the 2009 H1N1 global infection rate was 11% to 21%, lower than what was previously expected. However, by 2012, research showed that as many as 579,000 people could have been killed by the disease, as only those fatalities confirmed by laboratory testing were included in the original number, and meant that many without access to health facilities went uncounted. The majority of these deaths occurred in Africa and Southeast Asia. Experts, including the WHO, have agreed that an estimated 284,500 people were killed by the disease, much higher than the initial death toll. The symptoms of H1N1 flu are similar to those of other influenzas , and may include fever, cough (typically a "dry cough"), headache, dizziness, sneezing, muscle or joint pain, sore throat , chills , fatigue , and runny nose . Diarrhea , vomiting, and neurological problems have also been reported in some cases. People at higher risk of serious complications include people over 65, children younger than 5, children with neurodevelopmental conditions , pregnant women (especially during the third trimester), and people of any age with underlying medical conditions, such as asthma, diabetes, obesity, heart disease, or a weakened immune system (e.g., taking immunosuppressive medications or infected with HIV). More than 70% of hospitalizations in the U.S. have been people with such underlying conditions, according to the CDC . In September 2009, the CDC reported that the H1N1 flu "seems to be taking a heavier toll among chronically ill children than the seasonal flu usually does". Through 8 August 2009, the CDC had received 36 reports of pediatric deaths with associated influenza symptoms and laboratory-confirmed pandemic H1N1 from state and local health authorities within the United States, with 22 of these children having neurodevelopmental conditions such as cerebral palsy , muscular dystrophy , or developmental delays . "Children with nerve and muscle problems may be at especially high risk for complications because they cannot cough hard enough to clear their airways". From 26 April 2009, to 13 February 2010, the CDC had received reports of the deaths of 277 children with laboratory-confirmed 2009 influenza A (H1N1) within the United States. The World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit . Upon admission, most patients need immediate respiratory support with mechanical ventilation . Most complications have occurred among previously unhealthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation . Secondary bacterial infection is more common in children. Staphylococcus aureus , including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate; Streptococcus pneumoniae is the second most important cause of secondary bacterial pneumonia for children and primary for adults. Neuromuscular and cardiac complications are unusual but may occur. A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma , and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia , but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥ 100 mg/L) . 59% of all in-hospital deaths occurred in previously healthy people. Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died. Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism . In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli. An article published in JAMA in September 2010 challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. The World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit . Upon admission, most patients need immediate respiratory support with mechanical ventilation . Most complications have occurred among previously unhealthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation . Secondary bacterial infection is more common in children. Staphylococcus aureus , including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate; Streptococcus pneumoniae is the second most important cause of secondary bacterial pneumonia for children and primary for adults. Neuromuscular and cardiac complications are unusual but may occur. A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma , and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia , but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥ 100 mg/L) . 59% of all in-hospital deaths occurred in previously healthy people. Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died. Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism . In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli. An article published in JAMA in September 2010 challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. Confirmed diagnosis of pandemic H1N1 flu requires testing of a nasopharyngeal , nasal, or oropharyngeal tissue swab from the patient. Real-time RT-PCR is the recommended test as others are unable to differentiate between pandemic H1N1 and regular seasonal flu . However, most people with flu symptoms do not need a test for pandemic H1N1 flu specifically, because the test results usually do not affect the recommended course of treatment. The U.S. CDC recommend testing only for people who are hospitalized with suspected flu, pregnant women, and people with weakened immune systems. For the mere diagnosis of influenza and not pandemic H1N1 flu specifically, more widely available tests include rapid influenza diagnostic tests (RIDT), which yield results in about 30 minutes, and direct and indirect immunofluorescence assays ( DFA and IFA), which take 2–4 hours. Due to the high rate of RIDT false negatives , the CDC advises that patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications, and if a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. The use of RIDTs has been questioned by researcher Paul Schreckenberger of the Loyola University Health System, who suggests that rapid tests may actually pose a dangerous public health risk. Nikki Shindo of the WHO has expressed regret at reports of treatment being delayed by waiting for H1N1 test results and suggests, "[D]octors should not wait for the laboratory confirmation but make diagnosis based on clinical and epidemiological backgrounds and start treatment early." On 22 June 2010, the CDC announced a new test called the "CDC Influenza 2009 A (H1N1)pdm Real-Time RT-PCR Panel (IVD)". It uses a molecular biology technique to detect influenza A viruses and specifically the 2009 H1N1 virus. The new test will replace the previous real-time RT-PCR diagnostic test used during the 2009 H1N1 pandemic, which received an emergency use authorization from the U.S. Food and Drug Administration in April 2009. Tests results are available in four hours and are 96% accurate. The virus was found to be a novel strain of influenza for which existing vaccines against seasonal flu provided little protection. A study at the U.S. Centers for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain but that adults, particularly those older than 60, had some degree of immunity . Children showed no cross-reactive antibody reaction to the new strain, adults aged 18 to 60 had 6–9%, and older adults 33%. While it has been thought that these findings suggest the partial immunity in older adults may be due to previous exposure to similar seasonal influenza viruses, a November 2009 study of a rural unvaccinated population in China found only a 0.3% cross-reactive antibody reaction to the H1N1 strain, suggesting that previous vaccinations for seasonal flu and not exposure may have resulted in the immunity found in the older U.S. population. Analyses of the genetic sequences of the first isolates, promptly shared on the GISAID database according to Nature and WHO, soon determined that the strain contains genes from five different flu viruses: North American swine influenza, North American avian influenza, human influenza, and two swine influenza viruses typically found in Asia and Europe. Further analysis has shown that several proteins of the virus are most similar to strains that cause mild symptoms in humans, leading virologist Wendy Barclay to suggest on 1 May 2009, that the initial indications are that the virus was unlikely to cause severe symptoms for most people. The virus was less lethal than previous pandemic strains and killed about 0.01–0.03% of those infected; the 1918 influenza was about one hundred times more lethal and had a case fatality rate of 2–3%. By 14 November 2009, the virus had infected one in six Americans with 200,000 hospitalisations and 10,000 deaths—as many hospitalizations and fewer deaths than in an average flu season overall, but with much higher risk for those under 50. With deaths of 1,100 children and 7,500 adults 18 to 64, these figures were deemed "much higher than in a usual flu season" during the pandemic. In June 2010, scientists from Hong Kong reported discovery of a new swine flu virus: a hybrid of the pandemic H1N1 virus and viruses previously found in pigs. It was the first report of a reassortment of the pandemic virus, which in humans had been slow to evolve. Nancy Cox , head of the influenza division at the U.S. Centers for Disease Control and Prevention, has said, "This particular paper is extremely interesting because it demonstrates for the first time what we had worried about at the very onset of the pandemic, and that is that this particular virus, when introduced into pigs, could reassort with the resident viruses in pigs and we would have new gene constellations. And bingo, here we are." Pigs have been termed the mixing vessel of flu because they can be infected both by avian flu viruses, which rarely directly infect people, and by human viruses. When pigs become simultaneously infected with more than one virus, the viruses can swap genes, producing new variants which can pass to humans and sometimes spread amongst them. "Unlike the situation with birds and humans, we have a situation with pigs and humans where there's a two-way street of exchange of viruses. With pigs it's very much a two-way street." Spread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something—such as a surface or object—with flu viruses on it and then touching their face. The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75. A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms. The H1N1 virus has been transmitted to animals, including swine , turkeys , ferrets , household cats, at least one dog, and a cheetah . Spread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something—such as a surface or object—with flu viruses on it and then touching their face. The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75. A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms. The H1N1 virus has been transmitted to animals, including swine , turkeys , ferrets , household cats, at least one dog, and a cheetah . Because the H1N1 vaccine was initially in short supply in the U.S., the CDC recommended that initial doses should go to priority groups such as pregnant women, people who live with or care for babies under six months old, children six months to four years old and health-care workers. In the UK, the NHS recommended vaccine priority go to people over six months old who were clinically at risk for seasonal flu, pregnant women and households of people with compromised immunity. Although it was initially thought that two injections would be required, clinical trials showed that the new vaccine protected adults "with only one dose instead of two;" thus the limited vaccine supplies would go twice as far as had been predicted. Health officials worldwide were also concerned because the virus was new and could easily mutate and become more virulent, even though most flu symptoms were mild and lasted only a few days without treatment. Officials also urged communities, businesses, and individuals to make contingency plans for possible school closures, multiple employee absences for illness, surges of patients in hospitals, and other effects of potentially widespread outbreaks. Disaster response organizations such as Direct Relief helped by providing protective items to clinical workers to help them stay healthy throughout flu season. In February 2010, the CDC's Advisory Committee on Immunization Practices voted for "universal" flu vaccination in the U.S. to include all people over six months of age. The 2010–2011 vaccine will protect against the 2009 H1N1 pandemic virus and two other flu viruses. On 27 April 2009, the European Union health commissioner advised Europeans to postpone nonessential travel to the United States or Mexico. This followed the discovery of the first confirmed case in Spain. On 6 May 2009, the Public Health Agency of Canada announced that their National Microbiology Laboratory (NML) had mapped the genetic code of the swine flu virus, the first time that had been done. In the U.K., the National Health Service launched a website, the National Pandemic Flu Service, allowing patients to self-assess and get an authorisation number for antiviral medication. The system was expected to reduce the burden on general practitioners . U.S. officials observed that six years of concern about H5N1 avian flu did much to prepare for the current H1N1 outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected over the years, many countries took steps to try to prevent any similar crisis from spreading further. The CDC and other U.S. governmental agencies used the summer lull to take stock of the United States response to H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn. Preparations included planning a second influenza vaccination program in addition to the one for seasonal flu, and improving coordination between federal, state, and local governments and private health providers. On 24 October 2009, U.S. President Obama declared swine flu a national emergency, giving Secretary of Health and Human Services Kathleen Sebelius authority to grant waivers to requesting hospitals from usual federal requirements. By 19 November 2009, doses of vaccine had been administered in over 16 countries. A 2009 review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 vaccine has a safety profile similar to that of the seasonal vaccine. In 2011, a study from the US Flu Vaccine Effectiveness Network estimated the overall effectiveness of all pandemic H1N1 vaccines at 56%. A CDC study released 28 January 2013, estimated that the Pandemic H1N1 vaccine saved roughly 300 lives and prevented about a million illnesses in the US. The study concluded that had the vaccination program started two weeks earlier, close to 60% more cases could have been prevented. The study was based on an effectiveness in preventing cases, hospitalizations, and deaths of 62% for all subgroups except people over 65, for whom the effectiveness was estimated at 43%. The effectiveness was based on European and Asian studies and expert opinion. The delay in vaccine administration demonstrated the shortcomings of the world's capacity for vaccine-production, as well as problems with international distribution. Some manufacturers and wealthy countries had concerns regarding liability and regulations, as well as the logistics of transporting, storing, and administering vaccines to be donated to poorer countries. In January 2010, Wolfgang Wodarg , a German deputy who trained as a physician and chaired the health committee at the Council of Europe , claimed that major firms had organized a "campaign of panic" to put pressure on the World Health Organization (WHO) to declare a "false pandemic" to sell vaccines. Wodarg said the WHO's "false pandemic" flu campaign is "one of the greatest medicine scandals of the century". He said that the "false pandemic" campaign began in May 2009 in Mexico City , when a hundred or so "normal" reported influenza cases were declared to be the beginning of a threatening new pandemic, although he said there was little scientific evidence for it. Nevertheless, he argued that the WHO, "in cooperation with some big pharmaceutical companies and their scientists, re-defined pandemics," removing the statement that "an enormous amount of people have contracted the illness or died" from its existing definition and replacing it by stating simply that there has to be a virus, spreading beyond borders and to which people have no immunity. The WHO responded by stating that they take their duty to provide independent advice seriously and guarded against interference from outside interests. Announcing a review of the WHO's actions, spokeswoman Fadela Chaib stated: "Criticism is part of an outbreak cycle. We expect and indeed welcome criticism and the chance to discuss it". The WHO also stated on their website that "The world is going through a real pandemic. The description of it as a fake is wrong and irresponsible". In March 2010, the Council of Europe launched an enquiry into "the influence of the pharmaceutical companies on the global swine flu campaign", and a preliminary report was in preparation. On 12 April 2010, Keiji Fukuda, the WHO's top influenza expert, stated that the system leading to the declaration of a pandemic led to confusion about H1N1 circulating around the world and he expressed concern that there was a failure to communicate in regard to uncertainties about the new virus, which turned out to be not as deadly as feared. WHO Director-General Margaret Chan appointed 29 flu experts from outside the organization to conduct a review of WHO's handling of the H1N1 flu pandemic. She told them, "We want a frank, critical, transparent, credible and independent review of our performance." In June 2010, Fiona Godlee , editor-in-chief of the BMJ , published an editorial which criticised the WHO, saying that an investigation had disclosed that some of the experts advising WHO on the pandemic had financial ties with drug companies which were producing antivirals and vaccines. Margaret Chan, Director-General of the WHO, replied stating, "Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry. The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive". On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. On 27 April 2009, the European Union health commissioner advised Europeans to postpone nonessential travel to the United States or Mexico. This followed the discovery of the first confirmed case in Spain. On 6 May 2009, the Public Health Agency of Canada announced that their National Microbiology Laboratory (NML) had mapped the genetic code of the swine flu virus, the first time that had been done. In the U.K., the National Health Service launched a website, the National Pandemic Flu Service, allowing patients to self-assess and get an authorisation number for antiviral medication. The system was expected to reduce the burden on general practitioners . U.S. officials observed that six years of concern about H5N1 avian flu did much to prepare for the current H1N1 outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected over the years, many countries took steps to try to prevent any similar crisis from spreading further. The CDC and other U.S. governmental agencies used the summer lull to take stock of the United States response to H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn. Preparations included planning a second influenza vaccination program in addition to the one for seasonal flu, and improving coordination between federal, state, and local governments and private health providers. On 24 October 2009, U.S. President Obama declared swine flu a national emergency, giving Secretary of Health and Human Services Kathleen Sebelius authority to grant waivers to requesting hospitals from usual federal requirements. By 19 November 2009, doses of vaccine had been administered in over 16 countries. A 2009 review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 vaccine has a safety profile similar to that of the seasonal vaccine. In 2011, a study from the US Flu Vaccine Effectiveness Network estimated the overall effectiveness of all pandemic H1N1 vaccines at 56%. A CDC study released 28 January 2013, estimated that the Pandemic H1N1 vaccine saved roughly 300 lives and prevented about a million illnesses in the US. The study concluded that had the vaccination program started two weeks earlier, close to 60% more cases could have been prevented. The study was based on an effectiveness in preventing cases, hospitalizations, and deaths of 62% for all subgroups except people over 65, for whom the effectiveness was estimated at 43%. The effectiveness was based on European and Asian studies and expert opinion. The delay in vaccine administration demonstrated the shortcomings of the world's capacity for vaccine-production, as well as problems with international distribution. Some manufacturers and wealthy countries had concerns regarding liability and regulations, as well as the logistics of transporting, storing, and administering vaccines to be donated to poorer countries. In January 2010, Wolfgang Wodarg , a German deputy who trained as a physician and chaired the health committee at the Council of Europe , claimed that major firms had organized a "campaign of panic" to put pressure on the World Health Organization (WHO) to declare a "false pandemic" to sell vaccines. Wodarg said the WHO's "false pandemic" flu campaign is "one of the greatest medicine scandals of the century". He said that the "false pandemic" campaign began in May 2009 in Mexico City , when a hundred or so "normal" reported influenza cases were declared to be the beginning of a threatening new pandemic, although he said there was little scientific evidence for it. Nevertheless, he argued that the WHO, "in cooperation with some big pharmaceutical companies and their scientists, re-defined pandemics," removing the statement that "an enormous amount of people have contracted the illness or died" from its existing definition and replacing it by stating simply that there has to be a virus, spreading beyond borders and to which people have no immunity. The WHO responded by stating that they take their duty to provide independent advice seriously and guarded against interference from outside interests. Announcing a review of the WHO's actions, spokeswoman Fadela Chaib stated: "Criticism is part of an outbreak cycle. We expect and indeed welcome criticism and the chance to discuss it". The WHO also stated on their website that "The world is going through a real pandemic. The description of it as a fake is wrong and irresponsible". In March 2010, the Council of Europe launched an enquiry into "the influence of the pharmaceutical companies on the global swine flu campaign", and a preliminary report was in preparation. On 12 April 2010, Keiji Fukuda, the WHO's top influenza expert, stated that the system leading to the declaration of a pandemic led to confusion about H1N1 circulating around the world and he expressed concern that there was a failure to communicate in regard to uncertainties about the new virus, which turned out to be not as deadly as feared. WHO Director-General Margaret Chan appointed 29 flu experts from outside the organization to conduct a review of WHO's handling of the H1N1 flu pandemic. She told them, "We want a frank, critical, transparent, credible and independent review of our performance." In June 2010, Fiona Godlee , editor-in-chief of the BMJ , published an editorial which criticised the WHO, saying that an investigation had disclosed that some of the experts advising WHO on the pandemic had financial ties with drug companies which were producing antivirals and vaccines. Margaret Chan, Director-General of the WHO, replied stating, "Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry. The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive". On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. A number of methods have been recommended to help ease symptoms, including adequate liquid intake and rest. Over-the-counter pain medications such as paracetamol and ibuprofen do not kill the virus; however, they may be useful to reduce symptoms. Aspirin and other salicylate products should not be used by people under 16 with any flu-type symptoms because of the risk of developing Reye's Syndrome . If the fever is mild and there are no other complications, fever medication is not recommended. Most people recover without medical attention, although ones with pre-existing or underlying medical conditions are more prone to complications and may benefit from further treatments. People in at-risk groups should be treated with antivirals (oseltamivir or zanamivir) as soon as possible when they first experience flu symptoms. The at-risk groups include pregnant and post partum women, children under two years old, and people with underlying conditions such as respiratory problems. People who are not in an at-risk group who have persistent or rapidly worsening symptoms should also be treated with antivirals. People who have developed pneumonia should be given both antivirals and antibiotics, as in many severe cases of H1N1-caused illness, bacterial infection develops. Antivirals are most useful if given within 48 hours of the start of symptoms and may improve outcomes in hospitalised patients. In those beyond 48 hours who are moderately or severely ill, antivirals may still be beneficial. If oseltamivir (Tamiflu) is unavailable or cannot be used, zanamivir (Relenza) is recommended as a substitute. Peramivir is an experimental antiviral drug approved for hospitalised patients in cases where the other available methods of treatment are ineffective or unavailable. To help avoid shortages of these drugs, the U.S. CDC recommended oseltamivir treatment primarily for people hospitalised with pandemic flu; people at risk of serious flu complications due to underlying medical conditions; and patients at risk of serious flu complications. The CDC warned that the indiscriminate use of antiviral medications to prevent and treat influenza could ease the way for drug-resistant strains to emerge, which would make the fight against the pandemic that much harder. In addition, a British report found that people often failed to complete a full course of the drug or took the medication when not needed. Both medications mentioned above for treatment, oseltamivir and zanamivir, have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite, and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir. The WHO warned against buying antiviral medications from online sources and estimated that half the drugs sold by online pharmacies without a physical address were counterfeit. In December 2012, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir ( Tamiflu ). It is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir. No circulating flu has yet shown any resistance to zanamivir ( Relenza ), the other available anti-viral. On 8 December 2009, the Cochrane Collaboration , which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza. Of note, their published finding related only to use in healthy adults with influenza but not in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults still left it as a useful drug for reducing the duration of symptoms. In general, the Cochrane Collaboration concluded "Paucity of good data". Both medications mentioned above for treatment, oseltamivir and zanamivir, have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite, and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir. The WHO warned against buying antiviral medications from online sources and estimated that half the drugs sold by online pharmacies without a physical address were counterfeit. In December 2012, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir ( Tamiflu ). It is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir. No circulating flu has yet shown any resistance to zanamivir ( Relenza ), the other available anti-viral. On 8 December 2009, the Cochrane Collaboration , which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza. Of note, their published finding related only to use in healthy adults with influenza but not in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults still left it as a useful drug for reducing the duration of symptoms. In general, the Cochrane Collaboration concluded "Paucity of good data". Note: The ratio of confirmed deaths to total deaths due to the pandemic is unknown. For more information, see " Data reporting and accuracy ". While it is not known precisely where or when the virus originated, analyses in scientific journals have suggested that the H1N1 strain responsible for the 2009 outbreak first evolved in September 2008 and circulated amongst humans for several months, before being formally recognised and identified as a novel strain of influenza. The virus was first reported in two U.S. children in March 2009, but health officials have reported that it apparently infected people as early as January 2009 in Mexico. The outbreak was first identified in Mexico City on 18 March 2009; immediately after the outbreak was officially announced, Mexico notified the U.S. and World Health Organization, and within days of the outbreak Mexico City was "effectively shut down". Some countries cancelled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected. Mexico already had hundreds of non-lethal cases before the outbreak was officially discovered, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases which showed more severe signs different from those of normal flu, possibly leading to a skewed initial estimate of the case fatality rate. The new strain was first identified by the CDC in two children, neither of whom had been in contact with pigs. The first case, from San Diego County, California , was confirmed from clinical specimens ( nasopharyngeal swab ) examined by the CDC on 14 April 2009. A second case, from nearby Imperial County, California , was confirmed on 17 April. The patient in the first confirmed case had flu symptoms including fever and cough upon clinical examination on 30 March and the second on 28 March. The first confirmed H1N1/09 pandemic flu death, which occurred at Texas Children's Hospital in Houston, Texas, was of a toddler from Mexico City who was visiting family in Brownsville, Texas , before being air-lifted to Houston for treatment. The Infectious Diseases Society of America estimated that the total number of deaths in the U.S. was 12,469. Influenza surveillance information "answers the questions of where, when, and what influenza viruses are circulating. Sharing of such information is especially crucial during an emergent pandemic as in April 2009, when the genetic sequences of the initial viruses were rapidly and openly shared via the GISAID Initiative within days of identification, playing a key role in facilitating an early response to the evolving pandemic. Surveillance is used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza." For example, as of late June, influenza surveillance information showed the U.S. had nearly 28,000 laboratory-confirmed cases including 3,065 hospitalizations and 127 deaths. But mathematical modelling showed an estimated 1 million Americans had the 2009 pandemic flu at the time, according to Lyn Finelli , a flu surveillance official with the CDC. Estimating deaths from influenza is also a complicated process. In 2005, influenza only appeared on the death certificates of 1,812 people in the US. The average annual US death toll from flu is, however, estimated to be 36,000. The CDC explains: "[I]nfluenza is infrequently listed on death certificates of people who die from flu-related complications" and hence, "Only counting deaths where influenza was included on a death certificate would be a gross underestimation of influenza's true impact." Influenza surveillance information on the 2009 H1N1 flu pandemic is available, but almost no studies attempted to estimate the total number of deaths attributable to H1N1 flu. Two studies were carried out by the CDC; the later of them estimated that between 7,070 and 13,930 deaths were attributable to H1N1 flu from April to 14 November 2009. During the same period, 1,642 deaths were officially confirmed as caused by H1N1 flu. The WHO stated in 2010 that total mortality (including unconfirmed or unreported deaths) from H1N1 flu was "unquestionably higher" than their own confirmed death statistics. The initial outbreak received a week of near-constant media attention. Epidemiologists cautioned that the number of cases reported in the early days of an outbreak can be very inaccurate and deceptive, due to several causes, among them selection bias , media bias and incorrect reporting by governments. Inaccuracies could also be caused by authorities in different countries looking at differing population groups. Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases. "[E]ven in developed countries the [numbers of flu deaths] are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness". Joseph S. Bresee, then CDC flu division's epidemiology chief and Michael Osterholm , director of the Center for Infectious Disease Research and Policy pointed out that millions of people have had H1N1 flu, usually in a mild form, so the numbers of laboratory-confirmed cases were actually meaningless, and in July 2009, the WHO stopped keeping count of individual cases and focused more on major outbreaks. A Wisconsin study published in the Journal of the American Medical Association in September 2010, reported that findings showed that the 2009 H1N1 flu was no more severe than the seasonal flu. "The risk of most serious complications was not elevated in adults or children", the study's authors wrote. "Children were disproportionately affected by 2009 H1N1 infection, but the perceived severity of symptoms and risk of serious outcomes were not increased." Children infected in the 2009 H1N1 flu pandemic were no more likely to be hospitalized with complications or get pneumonia than those who catch seasonal strains. About 1.5% of children with the H1N1 swine flu strain were hospitalized within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. CDC illness and death estimates from April 2009 to April 2010, in the US are as follows: It has been stated that about 36,000 die from the seasonal flu in the U.S. each year, and this is frequently understood as an indication that the H1N1 strain was not as severe as seasonal influenza. The 36,000 estimate was presented in a 2003 study by CDC scientists and refers to a period from 1990 to 1991 through 1998–99. During those years, the number of estimated deaths ranged from 17,000 to 52,000, with an average of about 36,000. Throughout that decade, influenza A (H3N2) was the predominant virus during most of the seasons, and H3N2 influenza viruses are typically associated with higher death rates. The JAMA study also looked at seasonal influenza-associated deaths over a 23-year period, from 1976 to 1977 and 1998–99 with estimates of respiratory and circulatory influenza-associated deaths ranging from about 5,000 to about 52,000, and an average of about 25,000. CDC believes that the range of deaths over the past 31 years (~3,000 to ~49,000) is a more accurate representation of the unpredictability and variability of flu-associated deaths. The annual toll from seasonal influenza in the US between 1979 and 2001 is estimated at 41,400 deaths on average. Therefore, the H1N1 pandemic estimated mortality of 8,870 to 18,300 is just below the mid-range of estimates. The 2009 pandemic caused US hospitals to make significant preparations in terms of hospital surge capacities, especially within the emergency department and among vulnerable populations. In many cases, hospitals were relatively successful in making sure that those patients most severely affected by the influenza strain were able to be seen, treated, and discharged in an efficient manner. A case-study of the preparation, planning, mitigation, and response efforts during the fall of 2009 is that of the Children's Hospital of Philadelphia (CHOP) which took several steps to increase the emergency department (ED) surge capacity response. CHOP used portions of the main lobby area as an ED waiting room; several of the region's hospital-based outpatient facilities were in use during evening and weekend hours for non-emergency cases; the ED's 24-hour short-stay unit was utilized to care for ED patients in a longer-term capacity; non-board certified physicians (in pediatric emergency medicine) and inpatient-unit medical nurses were utilized for ED patient care; hospital units normally utilized for other medical or therapeutic purposes were transformed into ED patient rooms; and rooms normally used for only one patient were expanded to at least a capacity of 2. The virus was first reported in two U.S. children in March 2009, but health officials have reported that it apparently infected people as early as January 2009 in Mexico. The outbreak was first identified in Mexico City on 18 March 2009; immediately after the outbreak was officially announced, Mexico notified the U.S. and World Health Organization, and within days of the outbreak Mexico City was "effectively shut down". Some countries cancelled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected. Mexico already had hundreds of non-lethal cases before the outbreak was officially discovered, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases which showed more severe signs different from those of normal flu, possibly leading to a skewed initial estimate of the case fatality rate. The new strain was first identified by the CDC in two children, neither of whom had been in contact with pigs. The first case, from San Diego County, California , was confirmed from clinical specimens ( nasopharyngeal swab ) examined by the CDC on 14 April 2009. A second case, from nearby Imperial County, California , was confirmed on 17 April. The patient in the first confirmed case had flu symptoms including fever and cough upon clinical examination on 30 March and the second on 28 March. The first confirmed H1N1/09 pandemic flu death, which occurred at Texas Children's Hospital in Houston, Texas, was of a toddler from Mexico City who was visiting family in Brownsville, Texas , before being air-lifted to Houston for treatment. The Infectious Diseases Society of America estimated that the total number of deaths in the U.S. was 12,469. Influenza surveillance information "answers the questions of where, when, and what influenza viruses are circulating. Sharing of such information is especially crucial during an emergent pandemic as in April 2009, when the genetic sequences of the initial viruses were rapidly and openly shared via the GISAID Initiative within days of identification, playing a key role in facilitating an early response to the evolving pandemic. Surveillance is used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza." For example, as of late June, influenza surveillance information showed the U.S. had nearly 28,000 laboratory-confirmed cases including 3,065 hospitalizations and 127 deaths. But mathematical modelling showed an estimated 1 million Americans had the 2009 pandemic flu at the time, according to Lyn Finelli , a flu surveillance official with the CDC. Estimating deaths from influenza is also a complicated process. In 2005, influenza only appeared on the death certificates of 1,812 people in the US. The average annual US death toll from flu is, however, estimated to be 36,000. The CDC explains: "[I]nfluenza is infrequently listed on death certificates of people who die from flu-related complications" and hence, "Only counting deaths where influenza was included on a death certificate would be a gross underestimation of influenza's true impact." Influenza surveillance information on the 2009 H1N1 flu pandemic is available, but almost no studies attempted to estimate the total number of deaths attributable to H1N1 flu. Two studies were carried out by the CDC; the later of them estimated that between 7,070 and 13,930 deaths were attributable to H1N1 flu from April to 14 November 2009. During the same period, 1,642 deaths were officially confirmed as caused by H1N1 flu. The WHO stated in 2010 that total mortality (including unconfirmed or unreported deaths) from H1N1 flu was "unquestionably higher" than their own confirmed death statistics. The initial outbreak received a week of near-constant media attention. Epidemiologists cautioned that the number of cases reported in the early days of an outbreak can be very inaccurate and deceptive, due to several causes, among them selection bias , media bias and incorrect reporting by governments. Inaccuracies could also be caused by authorities in different countries looking at differing population groups. Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases. "[E]ven in developed countries the [numbers of flu deaths] are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness". Joseph S. Bresee, then CDC flu division's epidemiology chief and Michael Osterholm , director of the Center for Infectious Disease Research and Policy pointed out that millions of people have had H1N1 flu, usually in a mild form, so the numbers of laboratory-confirmed cases were actually meaningless, and in July 2009, the WHO stopped keeping count of individual cases and focused more on major outbreaks. A Wisconsin study published in the Journal of the American Medical Association in September 2010, reported that findings showed that the 2009 H1N1 flu was no more severe than the seasonal flu. "The risk of most serious complications was not elevated in adults or children", the study's authors wrote. "Children were disproportionately affected by 2009 H1N1 infection, but the perceived severity of symptoms and risk of serious outcomes were not increased." Children infected in the 2009 H1N1 flu pandemic were no more likely to be hospitalized with complications or get pneumonia than those who catch seasonal strains. About 1.5% of children with the H1N1 swine flu strain were hospitalized within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. CDC illness and death estimates from April 2009 to April 2010, in the US are as follows: It has been stated that about 36,000 die from the seasonal flu in the U.S. each year, and this is frequently understood as an indication that the H1N1 strain was not as severe as seasonal influenza. The 36,000 estimate was presented in a 2003 study by CDC scientists and refers to a period from 1990 to 1991 through 1998–99. During those years, the number of estimated deaths ranged from 17,000 to 52,000, with an average of about 36,000. Throughout that decade, influenza A (H3N2) was the predominant virus during most of the seasons, and H3N2 influenza viruses are typically associated with higher death rates. The JAMA study also looked at seasonal influenza-associated deaths over a 23-year period, from 1976 to 1977 and 1998–99 with estimates of respiratory and circulatory influenza-associated deaths ranging from about 5,000 to about 52,000, and an average of about 25,000. CDC believes that the range of deaths over the past 31 years (~3,000 to ~49,000) is a more accurate representation of the unpredictability and variability of flu-associated deaths. The annual toll from seasonal influenza in the US between 1979 and 2001 is estimated at 41,400 deaths on average. Therefore, the H1N1 pandemic estimated mortality of 8,870 to 18,300 is just below the mid-range of estimates. The 2009 pandemic caused US hospitals to make significant preparations in terms of hospital surge capacities, especially within the emergency department and among vulnerable populations. In many cases, hospitals were relatively successful in making sure that those patients most severely affected by the influenza strain were able to be seen, treated, and discharged in an efficient manner. A case-study of the preparation, planning, mitigation, and response efforts during the fall of 2009 is that of the Children's Hospital of Philadelphia (CHOP) which took several steps to increase the emergency department (ED) surge capacity response. CHOP used portions of the main lobby area as an ED waiting room; several of the region's hospital-based outpatient facilities were in use during evening and weekend hours for non-emergency cases; the ED's 24-hour short-stay unit was utilized to care for ED patients in a longer-term capacity; non-board certified physicians (in pediatric emergency medicine) and inpatient-unit medical nurses were utilized for ED patient care; hospital units normally utilized for other medical or therapeutic purposes were transformed into ED patient rooms; and rooms normally used for only one patient were expanded to at least a capacity of 2. Annual influenza epidemics are estimated to affect 5–15% of the global population. Although most cases are mild, these epidemics still cause severe illness in 3–5 million people and 290,000–650,000 deaths worldwide every year. On average 41,400 people die of influenza-related illnesses each year in the United States, based on data collected between 1979 and 2001. In industrialised countries, severe illness and deaths occur mainly in the high-risk populations of infants, the elderly and chronically ill patients, although the H1N1 flu outbreak (like the 1918 Spanish flu ) differs in its tendency to affect younger, healthier people. In addition to these annual epidemics, Influenza A virus strains caused three global pandemics during the 20th century: the Spanish flu in 1918, Asian flu in 1957, and Hong Kong flu in 1968–69. These virus strains had undergone major genetic changes for which the population did not possess significant immunity . Recent genetic analysis has revealed that three-quarters, or six out of the eight genetic segments, of the 2009 flu pandemic strain arose from the North American swine flu strains circulating since 1998, when a new strain was first identified on a factory farm in North Carolina, and which was the first-ever reported triple-hybrid flu virus. The Spanish flu began with a wave of mild cases in the spring, followed by more deadly waves in the autumn, eventually killing hundreds of thousands in the United States and 50–100 million worldwide. The great majority of deaths in the 1918 flu pandemic were the result of secondary bacterial pneumonia. The influenza virus damaged the lining of the bronchial tubes and lungs of patients, allowing common bacteria from the nose and throat to infect their lungs. Subsequent pandemics have had many fewer fatalities due to the development of antibiotic medicines which can treat pneumonia. The influenza virus has caused several pandemic threats over the past century, including the pseudo-pandemic of 1947 (thought of as mild because although globally distributed, it caused relatively few deaths), the 1976 swine flu outbreak and the 1977 Russian flu , all caused by the H1N1 subtype. The world has been at an increased level of alert since the SARS epidemic in Southeast Asia (caused by the SARS coronavirus ). The level of preparedness was further increased and sustained with the advent of the H5N1 bird flu outbreaks because of H5N1's high fatality rate, although the strains currently prevalent have limited human-to-human transmission ( anthroponotic ) capability, or epidemicity. People who contracted influenza before 1957 appeared to have some immunity to H1N1 flu. According to Daniel Jernigan, head of flu epidemiology for the U.S. CDC "Tests on blood serum from older people showed that they had antibodies that attacked the new virus ... That does not mean that everyone over 52 is immune, since Americans and Mexicans older than that have died of the new flu". In June 2012, a model based study found that the number of deaths related to the H1N1 influenza may have been fifteen times higher than the reported laboratory confirmed deaths, with 80% of the respiratory and cardiovascular deaths in people younger than 65 years and 51% occurring in southeast Asia and Africa. A disproportionate number of pandemic deaths might have occurred in these regions and that efforts to prevent future influenza pandemics need to effectively target these regions. A WHO-supported 2013 study estimated that the 2009 global pandemic respiratory mortality was ~10-fold higher than the World Health Organization's laboratory-confirmed mortality count (18.631). Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons less than 65 years of age occurred, so that many more life-years were lost. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last nine months of 2009. The majority (62–85%) were attributed to persons under 65 years of age. The burden varied greatly among countries. There was an almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000–249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 years of age. The COVID-19 pandemic is not caused by an influenza virus but SARS-CoV-2 , a coronavirus which also primarily affects the respiratory system.

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Spanish_flu_research/html

Spanish flu research

A/Brevig Mission/1/1918(H1N1) A/New_York/1/18(H1N1) A/AFIP/1/1918(H1N1) A/Iowa/1/1918(H1N1) A/London/1/1918(H1N1) A/London/1/1919(H1N1) ... Look for "/1918" on the full list of H1N1 strains Spanish flu research concerns studies regarding the causes and characteristics of the Spanish flu , a variety of influenza that in 1918 was responsible for the worst influenza pandemic in modern history. Many theories about the origins and progress of the Spanish flu persisted in the literature, but it was not until 2005, when various samples of lung tissue were recovered from American World War I soldiers and from an Inupiat woman buried in permafrost in a mass grave in Brevig Mission, Alaska , that significant genetic research was made possible.There are two prevailing theories usually postulated. [ citation needed ] One theory by Alfred W. Crosby is that the virus strain originated at Fort Riley , Kansas , by two genetic mechanisms – genetic drift and antigenic shift – in viruses in poultry and swine which the fort bred for local consumption. Though initial data from a recent reconstruction of the virus suggested that it jumped directly from birds to humans , without traveling through swine, [lower-alpha 1] this has since been cast into doubt. One researcher published in 2004 argued that the disease was found in Haskell County, Kansas , as early as January 1918. A similar and even more deadly virus had been seen earlier at British camps in France and at Aldershot. Earlier investigative work published in 2000 by a team led by British virologist, John Oxford of St Bartholomew's Hospital and the Royal London Hospital , suggested that a principal British troop staging camp in Étaples , France, was at the center of the 1918 flu pandemic or at least a significant precursor virus to it. There had been a mysterious respiratory infection at the military base during the winter of 1915–1916. In 1995, Jeffery Taubenberger of the US Armed Forces Institute of Pathology (AFIP), wondered if it might be possible to recover the virus of 1918 flu pandemic from the dried and fixed tissue of victims. He and his colleagues, tested 10 slides of tissue sample and 2 came out positive. Taubenberger, Ann H. Reid and Thomas G. Fanning were able to amplify short segments of the viral nucleic acid using polymerase chain reaction (PCR) . The results were published in the journal Science in March 1997. On August 20, 1997, Johan Hultin recovered samples of the 1918 influenza from the frozen corpse of a Native Alaskan woman buried for nearly eight decades in permafrost near Brevig Mission, Alaska . He brought the samples to a team in Rockville, Maryland led by Jeffery Taubenberger of the US Armed Forces Institute of Pathology (AFIP). Brevig Mission lost approximately 85% of its population to the 1918 flu in November 1918. One of the four recovered samples contained viable genetic material of the virus. This sample provided scientists a first-hand opportunity to study the virus, which was inactivated with guanidinium thiocyanate before transport. This sample and others found in AFIP archives allowed researchers to completely analyze the critical gene structures of the 1918 virus. The archived autopsy samples had been taken from WWI Army privates Roscoe Vaughan and James Downs. The 6 February 2004 edition of Science magazine reported that two research teams, one led by Sir John Skehel, director of the National Institute for Medical Research in London , another by professor Ian Wilson of The Scripps Research Institute in San Diego , had managed to synthesize the hemagglutinin protein responsible for the flu outbreak of 1918. They did this by piecing together DNA from a lung sample from an Inuit woman buried in the Alaskan tundra and a number of preserved samples from American soldiers of the First World War. The teams had analyzed the structure of the gene and discovered how subtle alterations to the shape of a protein molecule had allowed it to move from birds to humans with such devastating effects. On 5 October 2005, Tumpey and other researchers at the Centers for Disease Control and Prevention (CDC) in Atlanta , Georgia, and the Mount Sinai School of Medicine in New York , announced that the (~13 kbp) genetic sequence of the 1918 flu strain, a subtype of avian strain H1N1 , had been reconstructed using historic tissue samples and a small part of the RNA from a modern strain. Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses . The H5N1 virus has mutated into a variety of types with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. In July 2004, researchers led by H. Deng of the Harbin Veterinary Research Institute , Harbin , China, and Robert Webster of the St. Jude Children's Research Hospital , Memphis, Tennessee , reported results of experiments in which mice had been exposed to 21 isolates of confirmed H5N1 strains obtained from ducks in China between 1999 and 2002. They found "a clear temporal pattern of progressively increasing pathogenicity." Results reported by Webster in July 2005 reveal further progression toward pathogenicity in mice and longer virus shedding by ducks. In December 2008, research by Yoshihiro Kawaoka of University of Wisconsin showed the presence of the three specific genes (termed PA, PB1, and PB2) and a nucleoprotein derived from the H1N1 1918 flu samples was enough to trigger similar symptoms in animal testing. Recent research of Taubenberger et al. has suggested that the 1918 virus, like H5N1, could have arisen directly from an avian influenza virus. However, researchers at University of Virginia and Australian National University have suggested that there may be an alternative interpretation of the data used in the Taubenberger et al. paper. Taubenberger et al. responded to these letters and defended their original interpretation. Other research by Tumpey and colleagues who reconstructed the H1N1 virus of 1918 came to the conclusion that it was most notably the polymerase genes and the HA and NA genes that caused the extreme virulence of this virus. On 18 January 2007, Kobasa et al. reported that infected monkeys ( Macaca fascicularis ) exhibited classic symptoms of the 1918 pandemic and died from a cytokine storm . The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only 10 amino acids from the avian influenza viruses. Viruses with 7 of the 10 amino acids in the human influenza locations have already been identified in currently circulating H5N1 . This has led some researchers to suggest that other mutations may surface and make the H5N1 virus capable of human-to-human transmission. Another important factor is the change of the HA protein to a binding preference for alpha-2,6 sialic acid (the major form found in the human respiratory tract). In avian virus the HA protein preferentially binds to alpha-2,3 sialic acid, which is the major form in the avian enteric tract. It has been shown that only a single amino acid change can result in the change of this binding preference. Altogether, only a handful of mutations may need to take place in order for H5N1 avian flu to become a pandemic virus like the one of 1918. However it is important to note that likelihood of mutation does not indicate the likelihood for the evolution of such a strain, since some of the necessary mutations may be constrained by stabilizing selection .In the event of another pandemic, US military researchers have proposed reusing a treatment from the deadly pandemic of 1918 in order to blunt the effects of the flu: Some military doctors injected severely afflicted patients with blood or blood plasma from people who had recovered from the flu. Data collected during that time indicates that the blood-injection treatment reduced mortality rates by as much as 50 percent. Navy researchers have launched a test to see if the 1918 treatment will work against deadly Asian bird flu. Results thus far have been inconclusive. Human H5N1 plasma may be an effective, timely, and widely available treatment for the next flu pandemic. [ citation needed ] A new international study using modern data collection methods, would be a difficult, slow process. Citing the months-long wait for a vaccine for the next pandemic, many flu experts are of the opinion that the 1918 method is something to consider. In the worldwide 1918 flu pandemic , "physicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae – a name derived from the fact that it was originally considered the etiological agent – and several types of pneumococci). Only one therapeutic measure showed any hint of success: Transfusing blood from recovered patients to new victims."

Wiki

Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Marc_Siegel/html

Marc Siegel

Marc K. Siegel is an American physician, clinical professor of medicine at NYU Langone Medical Center , author, and contributor to The Hill , The Wall Street Journal , Slate , Fox News , and member of the board of contributors at USA Today . He is the medical director of NYU's Doctor Radio on Sirius XM . Siegel received his medical degree in 1985 from the State University of New York at Buffalo . He completed his residency in internal medicine in 1988 at the New York University Medical Center . He is board certified in internal medicine. In his books, columns, and interviews, Siegel suggested differentiated responses to infectious disease outbreaks, such as the swine flu , SARS , and avian influenza outbreaks. As a result, he has at times praised and at times criticized public health officials and the press for what he considered fearmongering about, or excessive focus on, certain outbreaks, arguing that resources should be directed toward other health threats. He has written three books promoting this view: False Alarm: the Truth About the Epidemic of Fear (2005), Bird Flu: Everything You Need to Know About the Next Pandemic (2006), and Swine Flu: The New Pandemic (2009). Siegel promoted his book False Alarm in a September 2005 appearance on The Daily Show with Jon Stewart . In 2001, Siegel recommended that individuals focus their health efforts based on the most likely ailments, rather than those that generate the most media. At the time, bovine spongiform encephalopathy ("mad cow disease") was generating headlines, but the average American woman faced a 1-in-3 lifetime chance of heart disease, a much higher risk. Siegel suggested focusing on everyday interventions that can produce large health impacts, rather than media-driven fears. During the 2009 outbreak of Swine flu, Siegel was a proponent of administering Tamiflu to children at summer camps "where there have been large, confirmed outbreaks" in order to stop the spread; Siegel said that he respectfully disagreed with the CDC's guidance to limit the use of Tamiflu in camps when lives could be saved with more aggressive treatments. During the COVID-19 pandemic in the United States , Siegel frequently appeared in media where he at times questioned the changing CDC guidelines and at times supported them. In January 2020, he "urge[d] people not to travel to China"; the following month he reported from the quarantine center where infected people from the Diamond Princess were in isolation, stating that "the virus appears to be more contagious than the flu and therefore very difficult to contain" and described PPE in use. In a March 2020 appearance on Fox News's Hannity , Siegel stated that, based on the declining case count in China at the time, COVID-19 "should be compared to the flu." A study by Kathleen Hall Jamieson and Dolores Albarracín , published in the peer-reviewed Harvard Kennedy School Misinformation Review in April 2020, identified Siegel's statement as part of a broader set of COVID-19 misinformation "circulating in conservative media." In July 2021, Siegel interviewed Dr. Fauci on SiriusXM's Doctor Radio, during which Dr. Fauci noted that masking may be required into 2022 to protect the vulnerable. In a 2022 interview with Siegel, Dr. Fauci discussed future boosters. In July 2021, Siegel urged TV viewers to get vaccinated, noting in a TV appearance that "the vaccine works extremely well even against the delta variant, preventing infection in 90 percent of cases." In August 2021, Siegel advocated for wider availability of booster shots as a means to provide enhanced protection to broader groups. Siegel's 2020 book, COVID: The Politics of Fear and the Power of Science , juxtaposes the meaningful scientific advancements in medicine of the last decades with the role of the media and politics in stoking extreme "doom and gloom" fears. The book examines technology that, prior to the pandemic, led to the healthiest and safest period in human history, and compares that to the decision-making process early in the pandemic. The Wall Street Journal reviewed it, stating "Dr. Siegel's chief argument is hard to dismiss: that fear, encouraged by a news media obsessed with doom and misery, has impelled public-health experts ... to impose draconian policies and ordinary Americans either to exaggerate or ignore moderately serious problems like Covid-19." Siegel at times praised parts of each of President Donald Trump 's and President Joe Biden's handling of the coronavirus pandemic. During the 2022–2023 mpox outbreak , Siegel praised the U.S. CDC for making changes to public health guidance that increased the likelihood of controlling the virus. He also praised improvements in real-time data collection that allowed refinements to public health messaging, an improvement over prior diseases. He urged faster distribution of vaccines and treatments to the hardest-hit areas. Siegel also compared the sanitation and rodent control of New York City and Los Angeles during the COVID pandemic, noting that New York was improving from its early-COVID proliferation of garbage, but Los Angeles was not. He predicted that these differences would lead to a difference in public health outcomes. Following the on-field cardiac arrest of Damar Hamlin and his subsequent recovery, Siegel compared the power of positive stories to unite the country with the divisiveness of DC politics, in particular the fight over the election of House Speaker Kevin McCarthy. Siegel criticized President Barack Obama over portions of his Patient Protection and Affordable Care Act (ACA) health care reform legislation because Siegel believed the legislation would result in narrower networks, increased deductibles, and reduced access to care. In 2017, Siegel wrote an op-ed in The New York Times that criticized the ACA and its essential health benefits provision (which he described as "an overstuffed prix fixe meal filled with benefits like maternity and mental health coverage") and praised the Republican legislation to repeal the ACA . During the repeal debate, Siegel supported Republican legislation that would limit "the menu of essential benefits" and instead create subsidized "high-risk pools" for uninsured patients with pre-existing conditions, although he also opposed "drastic cuts to Medicaid" supported Medicare expansion based on the success shown in Indiana and Ohio, and urged increased interstate competition for insurers. In 2018, Siegel published an opinion piece in support of the Affordable Care Act's requirement that restaurants make calorie information available to diners , noting studies that suggest calorie labeling can reduce intake by 30-40 calories daily, which adds up to a weight change of 3 to 5 pounds per year. During the Trump administration, Siegel interviewed then-President Trump about topics including his health, during which Trump described a cognitive evaluation as requiring him to remember " person, woman, man, camera, TV. " The phrase later became a meme. The interview was praised by the Columbia Journalism Review as prompting a "six-minute meander through Trump's thicket of self-diagnosis, during which the president mentioned China, Russia, Ukraine, judicial appointments, the Twenty-fifth Amendment, and, most notably, his ability to recite a string of five words while under observation by medical experts." Siegel advocates for public release of presidential candidate health records. Siegel reviewed the medical records of Senator John McCain during his 2000 presidential campaign, among others. In September 2016, Siegel urged then-candidates Hillary Clinton and Donald Trump to release their health records, noting Trump's weight and diet created risks regarding his ability to serve. In Fox News appearances during the 2016 U.S. presidential campaign , he urged the release of health records of candidate Hillary Clinton , in order to evaluate her physical fitness for office. In a USA Today opinion piece published April 2015, Siegel compared the public release of Senator John McCain's health records during his presidential campaign to Secretary Clinton's refusal to release hers. A further piece also published in April, this time in the Washington Times, repeated similar comparisons to past candidates' disclosures. Siegel has repeatedly ridden with President George W. Bush in his Warrior 100k annual three-day mountain bike ride, where they discussed the role of endurance exercise in healing physical wounds and behavioral challenges. In 2018, Barbara Bush entered hospice after ceasing aggressive treatment for lung and heart disease. Siegel said her choice showed "fortitude [and] courage." Similarly, when President Carter entered hospice care in 2023, Siegel discussed the legacy left by Carter as well as the opportunity to educate the public regarding palliative care . The mind-body problem refers to the challenge of reconciling neuro-physiology and consciousness in the human mind and brain. In The Inner Pulse: Unlocking the Secret Code of Sickness and Health (2011), Siegel describes medical miracles and posits a perceptible but ineffable and immeasurable "essential life force" "where the physical and the spiritual combine," advising readers to engage in practices to strengthen and focus it for use in overcoming disease and healing. It was reviewed in Publishers Weekly as "an intriguing approach to the mind/body conundrum." Siegel has hosted the SiriusXM radio show Doctor Radio Reports twice a week since March 2020, focusing on the impact of the COVID-19 pandemic and the efficacy of public health efforts to neutralize it. He is the medical director of Doctor Radio. In his books, columns, and interviews, Siegel suggested differentiated responses to infectious disease outbreaks, such as the swine flu , SARS , and avian influenza outbreaks. As a result, he has at times praised and at times criticized public health officials and the press for what he considered fearmongering about, or excessive focus on, certain outbreaks, arguing that resources should be directed toward other health threats. He has written three books promoting this view: False Alarm: the Truth About the Epidemic of Fear (2005), Bird Flu: Everything You Need to Know About the Next Pandemic (2006), and Swine Flu: The New Pandemic (2009). Siegel promoted his book False Alarm in a September 2005 appearance on The Daily Show with Jon Stewart . In 2001, Siegel recommended that individuals focus their health efforts based on the most likely ailments, rather than those that generate the most media. At the time, bovine spongiform encephalopathy ("mad cow disease") was generating headlines, but the average American woman faced a 1-in-3 lifetime chance of heart disease, a much higher risk. Siegel suggested focusing on everyday interventions that can produce large health impacts, rather than media-driven fears. During the 2009 outbreak of Swine flu, Siegel was a proponent of administering Tamiflu to children at summer camps "where there have been large, confirmed outbreaks" in order to stop the spread; Siegel said that he respectfully disagreed with the CDC's guidance to limit the use of Tamiflu in camps when lives could be saved with more aggressive treatments. During the COVID-19 pandemic in the United States , Siegel frequently appeared in media where he at times questioned the changing CDC guidelines and at times supported them. In January 2020, he "urge[d] people not to travel to China"; the following month he reported from the quarantine center where infected people from the Diamond Princess were in isolation, stating that "the virus appears to be more contagious than the flu and therefore very difficult to contain" and described PPE in use. In a March 2020 appearance on Fox News's Hannity , Siegel stated that, based on the declining case count in China at the time, COVID-19 "should be compared to the flu." A study by Kathleen Hall Jamieson and Dolores Albarracín , published in the peer-reviewed Harvard Kennedy School Misinformation Review in April 2020, identified Siegel's statement as part of a broader set of COVID-19 misinformation "circulating in conservative media." In July 2021, Siegel interviewed Dr. Fauci on SiriusXM's Doctor Radio, during which Dr. Fauci noted that masking may be required into 2022 to protect the vulnerable. In a 2022 interview with Siegel, Dr. Fauci discussed future boosters. In July 2021, Siegel urged TV viewers to get vaccinated, noting in a TV appearance that "the vaccine works extremely well even against the delta variant, preventing infection in 90 percent of cases." In August 2021, Siegel advocated for wider availability of booster shots as a means to provide enhanced protection to broader groups. Siegel's 2020 book, COVID: The Politics of Fear and the Power of Science , juxtaposes the meaningful scientific advancements in medicine of the last decades with the role of the media and politics in stoking extreme "doom and gloom" fears. The book examines technology that, prior to the pandemic, led to the healthiest and safest period in human history, and compares that to the decision-making process early in the pandemic. The Wall Street Journal reviewed it, stating "Dr. Siegel's chief argument is hard to dismiss: that fear, encouraged by a news media obsessed with doom and misery, has impelled public-health experts ... to impose draconian policies and ordinary Americans either to exaggerate or ignore moderately serious problems like Covid-19." Siegel at times praised parts of each of President Donald Trump 's and President Joe Biden's handling of the coronavirus pandemic. During the 2022–2023 mpox outbreak , Siegel praised the U.S. CDC for making changes to public health guidance that increased the likelihood of controlling the virus. He also praised improvements in real-time data collection that allowed refinements to public health messaging, an improvement over prior diseases. He urged faster distribution of vaccines and treatments to the hardest-hit areas. Siegel also compared the sanitation and rodent control of New York City and Los Angeles during the COVID pandemic, noting that New York was improving from its early-COVID proliferation of garbage, but Los Angeles was not. He predicted that these differences would lead to a difference in public health outcomes. Following the on-field cardiac arrest of Damar Hamlin and his subsequent recovery, Siegel compared the power of positive stories to unite the country with the divisiveness of DC politics, in particular the fight over the election of House Speaker Kevin McCarthy. In his books, columns, and interviews, Siegel suggested differentiated responses to infectious disease outbreaks, such as the swine flu , SARS , and avian influenza outbreaks. As a result, he has at times praised and at times criticized public health officials and the press for what he considered fearmongering about, or excessive focus on, certain outbreaks, arguing that resources should be directed toward other health threats. He has written three books promoting this view: False Alarm: the Truth About the Epidemic of Fear (2005), Bird Flu: Everything You Need to Know About the Next Pandemic (2006), and Swine Flu: The New Pandemic (2009). Siegel promoted his book False Alarm in a September 2005 appearance on The Daily Show with Jon Stewart . In 2001, Siegel recommended that individuals focus their health efforts based on the most likely ailments, rather than those that generate the most media. At the time, bovine spongiform encephalopathy ("mad cow disease") was generating headlines, but the average American woman faced a 1-in-3 lifetime chance of heart disease, a much higher risk. Siegel suggested focusing on everyday interventions that can produce large health impacts, rather than media-driven fears. During the 2009 outbreak of Swine flu, Siegel was a proponent of administering Tamiflu to children at summer camps "where there have been large, confirmed outbreaks" in order to stop the spread; Siegel said that he respectfully disagreed with the CDC's guidance to limit the use of Tamiflu in camps when lives could be saved with more aggressive treatments. During the COVID-19 pandemic in the United States , Siegel frequently appeared in media where he at times questioned the changing CDC guidelines and at times supported them. In January 2020, he "urge[d] people not to travel to China"; the following month he reported from the quarantine center where infected people from the Diamond Princess were in isolation, stating that "the virus appears to be more contagious than the flu and therefore very difficult to contain" and described PPE in use. In a March 2020 appearance on Fox News's Hannity , Siegel stated that, based on the declining case count in China at the time, COVID-19 "should be compared to the flu." A study by Kathleen Hall Jamieson and Dolores Albarracín , published in the peer-reviewed Harvard Kennedy School Misinformation Review in April 2020, identified Siegel's statement as part of a broader set of COVID-19 misinformation "circulating in conservative media." In July 2021, Siegel interviewed Dr. Fauci on SiriusXM's Doctor Radio, during which Dr. Fauci noted that masking may be required into 2022 to protect the vulnerable. In a 2022 interview with Siegel, Dr. Fauci discussed future boosters. In July 2021, Siegel urged TV viewers to get vaccinated, noting in a TV appearance that "the vaccine works extremely well even against the delta variant, preventing infection in 90 percent of cases." In August 2021, Siegel advocated for wider availability of booster shots as a means to provide enhanced protection to broader groups. Siegel's 2020 book, COVID: The Politics of Fear and the Power of Science , juxtaposes the meaningful scientific advancements in medicine of the last decades with the role of the media and politics in stoking extreme "doom and gloom" fears. The book examines technology that, prior to the pandemic, led to the healthiest and safest period in human history, and compares that to the decision-making process early in the pandemic. The Wall Street Journal reviewed it, stating "Dr. Siegel's chief argument is hard to dismiss: that fear, encouraged by a news media obsessed with doom and misery, has impelled public-health experts ... to impose draconian policies and ordinary Americans either to exaggerate or ignore moderately serious problems like Covid-19." Siegel at times praised parts of each of President Donald Trump 's and President Joe Biden's handling of the coronavirus pandemic. During the 2022–2023 mpox outbreak , Siegel praised the U.S. CDC for making changes to public health guidance that increased the likelihood of controlling the virus. He also praised improvements in real-time data collection that allowed refinements to public health messaging, an improvement over prior diseases. He urged faster distribution of vaccines and treatments to the hardest-hit areas. Siegel also compared the sanitation and rodent control of New York City and Los Angeles during the COVID pandemic, noting that New York was improving from its early-COVID proliferation of garbage, but Los Angeles was not. He predicted that these differences would lead to a difference in public health outcomes. Following the on-field cardiac arrest of Damar Hamlin and his subsequent recovery, Siegel compared the power of positive stories to unite the country with the divisiveness of DC politics, in particular the fight over the election of House Speaker Kevin McCarthy. Siegel criticized President Barack Obama over portions of his Patient Protection and Affordable Care Act (ACA) health care reform legislation because Siegel believed the legislation would result in narrower networks, increased deductibles, and reduced access to care. In 2017, Siegel wrote an op-ed in The New York Times that criticized the ACA and its essential health benefits provision (which he described as "an overstuffed prix fixe meal filled with benefits like maternity and mental health coverage") and praised the Republican legislation to repeal the ACA . During the repeal debate, Siegel supported Republican legislation that would limit "the menu of essential benefits" and instead create subsidized "high-risk pools" for uninsured patients with pre-existing conditions, although he also opposed "drastic cuts to Medicaid" supported Medicare expansion based on the success shown in Indiana and Ohio, and urged increased interstate competition for insurers. In 2018, Siegel published an opinion piece in support of the Affordable Care Act's requirement that restaurants make calorie information available to diners , noting studies that suggest calorie labeling can reduce intake by 30-40 calories daily, which adds up to a weight change of 3 to 5 pounds per year. During the Trump administration, Siegel interviewed then-President Trump about topics including his health, during which Trump described a cognitive evaluation as requiring him to remember " person, woman, man, camera, TV. " The phrase later became a meme. The interview was praised by the Columbia Journalism Review as prompting a "six-minute meander through Trump's thicket of self-diagnosis, during which the president mentioned China, Russia, Ukraine, judicial appointments, the Twenty-fifth Amendment, and, most notably, his ability to recite a string of five words while under observation by medical experts." Siegel advocates for public release of presidential candidate health records. Siegel reviewed the medical records of Senator John McCain during his 2000 presidential campaign, among others. In September 2016, Siegel urged then-candidates Hillary Clinton and Donald Trump to release their health records, noting Trump's weight and diet created risks regarding his ability to serve. In Fox News appearances during the 2016 U.S. presidential campaign , he urged the release of health records of candidate Hillary Clinton , in order to evaluate her physical fitness for office. In a USA Today opinion piece published April 2015, Siegel compared the public release of Senator John McCain's health records during his presidential campaign to Secretary Clinton's refusal to release hers. A further piece also published in April, this time in the Washington Times, repeated similar comparisons to past candidates' disclosures. Siegel has repeatedly ridden with President George W. Bush in his Warrior 100k annual three-day mountain bike ride, where they discussed the role of endurance exercise in healing physical wounds and behavioral challenges. In 2018, Barbara Bush entered hospice after ceasing aggressive treatment for lung and heart disease. Siegel said her choice showed "fortitude [and] courage." Similarly, when President Carter entered hospice care in 2023, Siegel discussed the legacy left by Carter as well as the opportunity to educate the public regarding palliative care . The mind-body problem refers to the challenge of reconciling neuro-physiology and consciousness in the human mind and brain. In The Inner Pulse: Unlocking the Secret Code of Sickness and Health (2011), Siegel describes medical miracles and posits a perceptible but ineffable and immeasurable "essential life force" "where the physical and the spiritual combine," advising readers to engage in practices to strengthen and focus it for use in overcoming disease and healing. It was reviewed in Publishers Weekly as "an intriguing approach to the mind/body conundrum." Siegel has hosted the SiriusXM radio show Doctor Radio Reports twice a week since March 2020, focusing on the impact of the COVID-19 pandemic and the efficacy of public health efforts to neutralize it. He is the medical director of Doctor Radio. Siegel was born on June 15, 1956, in New York. He is married to Ludmilla Luda Siegel, who is a physician and neurologist. They have three children. Siegel is Jewish and cites the Oath of Maimonides as a medical ethics influence. He attended East Meadow High School . Following high school, he went to Brown University in Providence, Rhode Island, from 1974 to 1978. He received his Doctor of Medicine degree in 1985 from the State University of New York at Buffalo . He completed his residency in internal medicine in 1988 at New York University Medical Center . [ unreliable source ]

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Avian influenza

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Water bird

A water bird , alternatively waterbird or aquatic bird , is a bird that lives on or around water. In some definitions, the term water bird is especially applied to birds in freshwater ecosystems , although others make no distinction from seabirds that inhabit marine environments . Some water birds (e.g. wading birds ) are more terrestrial while others (e.g. waterfowls ) are more aquatic, and their adaptations will vary depending on their environment. These adaptations include webbed feet , beaks, and legs adapted to feed in the water, and the ability to dive from the surface or the air to catch prey in water. The term aquatic bird is sometimes also used in this context. A related term that has a narrower meaning is waterfowl . Some piscivorous birds of prey , such as ospreys and sea eagles , hunt aquatic prey but do not stay in water for long and live predominantly over dry land, and are not considered water birds. The term waterbird is also used in the context of conservation to refer to any birds that inhabit or depend on bodies of water or wetland areas. Examples of this use include the Agreement on the Conservation of African-Eurasian Migratory Waterbirds (AEWA) and the Wallnau Waterbird Reserve .Some examples of water birds are:The evolution of waterbirds is often mainly centered around adaptations to improve feeding techniques. This includes legs that are adapted to diving or wading and webbing between the toes. Many of these adaptations are common between different types of waterbirds. For example, flamingos and ducks share a similar filter-feeding lifestyle, and the shoebill has a similar structure ( morphology ) to many wading birds. DNA sequence analysis, specifically the mitochondrial gene sequencing, has been used to classify and differentiate the various aquatic birds. This classification is found by a relative apparent synapomorphy analysis (RASA) which highlighted certain branches of genes that classified the domestic duck and fowl, for example, as an outgroup. Comparing and understanding these gene patterns allows scientists to classify aquatic birds. Waterbird conservation efforts in the United States are advanced by numerous organizations, including the 700,000 member strong Ducks Unlimited . Employing such methods as conservation easements and outright purchase, it uses federal and state habitat reimbursements, sponsorships, member fees, major gifts, donations, royalties, and advertisement to raise over $200 million a year. A minimum of 80 percent of that revenue goes directly toward habitat conservation . Ducks Unlimited partners with a wide range of corporations, governments, other non-governmental organizations, landowners, and private citizens to restore and manage areas that have been degraded and to prevent further degradation of existing wetlands. DU is also active in working with others to recommend government policies that will influence wetlands and the environment. Through March 2021 Ducks Unlimited had conserved at least 15 million acres of waterfowl habitat in North America. To promote the conservation of waterbirds in America, the United States Fish and Wildlife Service established the Waterbird Conservation for the Americas to facilitate this over such a large area. The purpose of this initiative is to promote international cooperation and partnership to preserve waterbird habitats, create long term sustainability plans, implement specific conservation plans for regions, and support legal action for waterbird conservation on the regional and national levels. The loss of wetlands has impacted waterbirds and is driving their extinction in regions where wetlands are polluted. Specifically, in China, 33% of wetlands were lost between 1978 and 2008, which is the primary breeding ground for China's waterbird species such as the Baer's Pochard, which is now at risk for extinction. The Baer's Pochard's population has decreased to between 150 and 700 birds in recent years due to negative environmental impacts on their habitat as well as human activities such as hunting and fishing. This loss of wetlands is a result of various sources in China. The rise of urbanization and industries has resulted in pollution and waste in the water. In addition, reclamation projects for construction further threaten ruining the habitats of these birds. For example, the largest of these reclamation projects is the Oufei Project, which spans 8854 Hectares. Experimental evidence of competition has been difficult to obtain in highly mobile animals that cannot be meaningfully confined to plots of limited size. Many such animals are believed to compete with less mobile, resident taxa, but the supporting evidence has often remained circumstantial. One example is the interaction between water birds and benthic feeding fish, or fish that feed at the lowest level of a body of water. Many migratory water birds use similar food resources on their breeding, molting, or overwintering grounds as do resident fish species. Studies, such as that done by Eadie and Keast in 1982, found an inverse relationship between the waterbird Goldeneye and benthic feeding fish across multiple lakes. Mobile water birds avoid areas where their food density is high because this increases competition for resources. When there is a lot of food in an area, there are more birds trying to eat it. This can lead to aggression and fighting, as well as a decrease in the overall fitness of the bird. By avoiding areas of high food density, mobile waterfowl can reduce competition and improve their chances of survival. They can spread out and forage in less crowded areas, which allows them to avoid conflict and obtain the nutrients they need. Outbreaks of diseases spread by waterbirds result from the transition of water-borne viruses to those wild birds. The spread can be caused by dead waterbirds in the vicinity of other organisms, or simply from waterbirds with the virus settling into more densely populated areas (whether by humans or other organisms). Duck plague (DP), also called duck enteritis virus (DEV), presents the most important concern in mass waterfowl production. Free-ranging water birds are the most likely infectious carriers. While the overall epidemiology of DEV is unknown in western Europe, studies conducted in Poland agree with the high levels of transmission between free-ranging water birds. DEV is an aetiological agent of DP, which represents one of the most acute and lethal diseases of waterbirds, and infection can spread easily between farmed and wild waterbirds. Over 48 species of birds, including those not considered waterbirds, are susceptible to infection by DEV, and the mortality rate of this disease can reach up to 100%, especially in young birds. Avian influenza caused by infection with H5N1 , a highly pathogenic avian influenza virus (HPAIV), has spread in poultry in more than 60 countries in Eurasia and Africa since 1996, when the first outbreak occurred at a goose farm in Guangdong province in China. H5N1 in wild birds have spread to Asia, Europe, and Africa, and it is possible for the H5N1 virus to be spread by migratory water birds to the west and south, as genetically closely related H5N1 viruses have been isolated in several countries since 2005. H5N1 HPAIV infections have become endemic in several countries and cause accidental transmissions to humans. H5N1 viruses are thus now recognized as one of the most likely candidates for the next pandemic. Duck plague (DP), also called duck enteritis virus (DEV), presents the most important concern in mass waterfowl production. Free-ranging water birds are the most likely infectious carriers. While the overall epidemiology of DEV is unknown in western Europe, studies conducted in Poland agree with the high levels of transmission between free-ranging water birds. DEV is an aetiological agent of DP, which represents one of the most acute and lethal diseases of waterbirds, and infection can spread easily between farmed and wild waterbirds. Over 48 species of birds, including those not considered waterbirds, are susceptible to infection by DEV, and the mortality rate of this disease can reach up to 100%, especially in young birds. Avian influenza caused by infection with H5N1 , a highly pathogenic avian influenza virus (HPAIV), has spread in poultry in more than 60 countries in Eurasia and Africa since 1996, when the first outbreak occurred at a goose farm in Guangdong province in China. H5N1 in wild birds have spread to Asia, Europe, and Africa, and it is possible for the H5N1 virus to be spread by migratory water birds to the west and south, as genetically closely related H5N1 viruses have been isolated in several countries since 2005. H5N1 HPAIV infections have become endemic in several countries and cause accidental transmissions to humans. H5N1 viruses are thus now recognized as one of the most likely candidates for the next pandemic.

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Avian influenza

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Scavenger

Scavengers are animals that consume dead organisms that have died from causes other than predation or have been killed by other predators. While scavenging generally refers to carnivores feeding on carrion , it is also a herbivorous feeding behavior . Scavengers play an important role in the ecosystem by consuming dead animal and plant material. Decomposers and detritivores complete this process, by consuming the remains left by scavengers. Scavengers aid in overcoming fluctuations of food resources in the environment. The process and rate of scavenging is affected by both biotic and abiotic factors, such as carcass size, habitat, temperature, and seasons. Scavenger is an alteration of scavager, from Middle English skawager meaning " customs collector", from skawage meaning "customs", from Old North French escauwage meaning "inspection", from schauwer meaning "to inspect", of Germanic origin; akin to Old English scēawian and German schauen meaning "to look at", and modern English "show" (with semantic drift ).Obligate scavenging (subsisting entirely or mainly on dead animals) is rare among vertebrates, due to the difficulty of finding enough carrion without expending too much energy. Well-known invertebrate scavengers of animal material include burying beetles and blowflies , which are obligate scavengers, and yellowjackets . Fly larvae are also common scavengers for organic materials at the bottom of freshwater bodies. For example, Tokunagayusurika akamusi is a species of midge fly whose larvae live as obligate scavengers at the bottom of lakes and whose adults almost never feed and only live up to a few weeks. Most scavenging animals are facultative scavengers that gain most of their food through other methods, especially predation . Many large carnivores that hunt regularly, such as hyenas and jackals , but also animals rarely thought of as scavengers, such as African lions , leopards , and wolves will scavenge if given the chance. They may also use their size and ferocity to intimidate the original hunters (the cheetah is a notable victim, rather than a perpetrator). Almost all scavengers above insect size are predators and will hunt if not enough carrion is available, as few ecosystems provide enough dead animals year-round to keep its scavengers fed on that alone. Scavenging wild dogs and crows frequently exploit roadkill . Scavengers of dead plant material include termites that build nests in grasslands and then collect dead plant material for consumption within the nest. The interaction between scavenging animals and humans is seen today most commonly in suburban settings with animals such as opossums, polecats and raccoons . In some African towns and villages, scavenging from hyenas is also common. In the prehistoric eras, the species Tyrannosaurus rex may have been an apex predator , preying upon hadrosaurs , ceratopsians , and possibly juvenile sauropods, although some experts have suggested the dinosaur was primarily a scavenger. The debate about whether Tyrannosaurus was an apex predator or scavenger was among the longest ongoing feuds in paleontology ; however, most scientists now agree that Tyrannosaurus was an opportunistic carnivore, acting mostly as a predator but also scavenging when it could sense it. Recent research also shows that while an adult T. rex would energetically gain little through scavenging, smaller theropods of approximately 500 kg (1,100 lb) might have gained levels similar to those of hyenas, though not enough for them to rely on scavenging. Other research suggests that carcasses of giant sauropods may have made scavenging much more profitable to carnivores than it is now. For example, a single 40 tonne Apatosaurus carcass would have been worth roughly 6 years of calories for an average allosaur. As a result of this resource oversupply, it is possible that some theropods evolved to get most of their calories by scavenging giant sauropod carcasses, and may not have needed to consistently hunt in order to survive. The same study suggested that theropods in relatively sauropod-free environments, such as tyrannosaurs, were not exposed to the same type of carrion oversupply, and were therefore forced to hunt in order to survive. Animals which consume feces , such as dung beetles , are referred to as coprovores . Animals that collect small particles of dead organic material of both animal and plant origin are referred to as detritivores .Scavengers play a fundamental role in the environment through the removal of decaying organisms, serving as a natural sanitation service. While microscopic and invertebrate decomposers break down dead organisms into simple organic matter which are used by nearby autotrophs , scavengers help conserve energy and nutrients obtained from carrion within the upper trophic levels , and are able to disperse the energy and nutrients farther away from the site of the carrion than decomposers. Scavenging unites animals which normally would not come into contact, and results in the formation of highly structured and complex communities which engage in nonrandom interactions. Scavenging communities function in the redistribution of energy obtained from carcasses and reducing diseases associated with decomposition. Oftentimes, scavenger communities differ in consistency due to carcass size and carcass types, as well as by seasonal effects as consequence of differing invertebrate and microbial activity. Competition for carrion results in the inclusion or exclusion of certain scavengers from access to carrion, shaping the scavenger community. When carrion decomposes at a slower rate during cooler seasons, competitions between scavengers decrease, while the number of scavenger species present increases. Alterations in scavenging communities may result in drastic changes to the scavenging community in general, reduce ecosystem services and have detrimental effects on animal and humans. The reintroduction of gray wolves ( Canis lupus ) into Yellowstone National Park in the United States caused drastic changes to the prevalent scavenging community, resulting in the provision of carrion to many mammalian and avian species. Likewise, the reduction of vulture species in India lead to the increase of opportunistic species such as feral dogs and rats. The presence of both species at carcasses resulted in the increase of diseases such as rabies and bubonic plague in wildlife and livestock, as feral dogs and rats are transmitters of such diseases. Furthermore, the decline of vulture populations in India has been linked to the increased rates of anthrax in humans due to the handling and ingestion of infected livestock carcasses. An increase of disease transmission has been observed in mammalian scavengers in Kenya due to the decrease in vulture populations in the area, as the decrease in vulture populations resulted in an increase of the number of mammalian scavengers at a given carcass along with the time spent at a carcass. Scavenging may provide a direct and indirect method for transmitting disease between animals. Scavengers of infected carcasses may become hosts for certain pathogens and consequently vectors of disease themselves. An example of this phenomenon is the increased transmission of tuberculosis observed when scavengers engage in eating infected carcasses. Likewise, the ingestion of bat carcasses infected with rabies by striped skunks ( Mephitis mephitis ) resulted in increased infection of these organisms with the virus. A major vector of transmission of diseases are various bird species, with outbreak being influenced by such carrier birds and their environment. An avian cholera outbreak from 2006 to 2007 off the coast Newfoundland, Canada resulted in the mortality of many marine bird species. The transmission, perpetuation and spread of the outbreak was mainly restricted to gull species who scavenge for food in the area. Similarly, an increase of transmission of avian influenza virus to chickens by domestic ducks from Indonesian farms permitted to scavenge surrounding areas was observed in 2007. The scavenging of ducks in rice paddy fields in particular resulted in increased contact with other bird species feeding on leftover rice, which may have contributed to increased infection and transmission of the avian influenza virus. The domestic ducks may not have demonstrated symptoms of infection themselves, though were observed to excrete high concentrations of the avian influenza virus. Scavenging may provide a direct and indirect method for transmitting disease between animals. Scavengers of infected carcasses may become hosts for certain pathogens and consequently vectors of disease themselves. An example of this phenomenon is the increased transmission of tuberculosis observed when scavengers engage in eating infected carcasses. Likewise, the ingestion of bat carcasses infected with rabies by striped skunks ( Mephitis mephitis ) resulted in increased infection of these organisms with the virus. A major vector of transmission of diseases are various bird species, with outbreak being influenced by such carrier birds and their environment. An avian cholera outbreak from 2006 to 2007 off the coast Newfoundland, Canada resulted in the mortality of many marine bird species. The transmission, perpetuation and spread of the outbreak was mainly restricted to gull species who scavenge for food in the area. Similarly, an increase of transmission of avian influenza virus to chickens by domestic ducks from Indonesian farms permitted to scavenge surrounding areas was observed in 2007. The scavenging of ducks in rice paddy fields in particular resulted in increased contact with other bird species feeding on leftover rice, which may have contributed to increased infection and transmission of the avian influenza virus. The domestic ducks may not have demonstrated symptoms of infection themselves, though were observed to excrete high concentrations of the avian influenza virus. Many species that scavenge face persecution globally. [ citation needed ] Vultures, in particular, have faced incredible persecution and threats by humans. Before its ban by regional governments in 2006, the veterinary drug Diclofenac has resulted in at least a 95% decline of Gyps vultures in Asia. Habitat loss and food shortage have contributed to the decline of vulture species in West Africa due to the growing human population and over-hunting of vulture food sources, as well as changes in livestock husbandry. Poisoning certain predators to increase the number of game animals is still a common hunting practice in Europe and contributes to the poisoning of vultures when they consume the carcasses of poisoned predators. Highly efficient scavengers, also known as dominant or apex-scavengers, can have benefits to humans. Increases in dominant scavenger populations, such as vultures, can reduce populations of smaller opportunistic scavengers, such as rats. These smaller scavengers are often pests and disease vectors.In the 1980s, Lewis Binford suggested that early humans primarily obtained meat via scavenging , not through hunting . In 2010, Dennis Bramble and Daniel Lieberman proposed that early carnivorous human ancestors subsequently developed long-distance running behaviors which improved the ability to scavenge and hunt: they could reach scavenging sites more quickly and also pursue a single animal until it could be safely killed at close range due to exhaustion and hyperthermia. In Tibetan Buddhism the practice of excarnation – that is, the exposure of dead human bodies to carrion birds and/or other scavenging animals – is the distinctive characteristic of sky burial , which involves the dismemberment of human cadavers of whom the remains are fed to vultures , and traditionally the main funeral rite (alongside cremation ) used to dispose of the human body. A similar funerary practice that features excarnation can be found in Zoroastrianism ; in order to prevent the pollution of the sacred elements (fire, earth, and water) from contact with decomposing bodies , human cadavers are exposed on the Towers of Silence to be eaten by vultures and wild dogs. Studies in behavioral ecology and ecological epidemiology have shown that cannibalistic necrophagy , although rare, has been observed as a survival behavior in several social species , including anatomically modern humans ; however, episodes of human cannibalism occur rarely in most human societies. [Note 1] Many instances have occurred in human history , especially in times of war and famine , where necrophagy and human cannibalism emerged as a survival behavior, although anthropologists report the usage of ritual cannibalism among funerary practices and as the preferred means of disposal of the dead in some tribal societies .

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Avian influenza

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International Partnership on Avian and Pandemic Influenza

President George W. Bush announced the International Partnership on Avian and Pandemic Influenza in his remarks to the High-Level Plenary Meeting of the United Nations General Assembly on September 14, 2005, in New York. On September 15, 2005, Under Secretary of State for Democracy and Global Affairs Dr. Paula Dobriansky was joined by the Director General of the World Health Organization Dr. Lee Jong-wook , Executive Director of UNICEF Ann Veneman , and senior representatives from several participating countries to describe the Partnerships goals of improving global readiness by: elevating the issue on national agendas; coordinating efforts among donor and affected nations; mobilizing and leveraging resources; increasing transparency in disease reporting and surveillance; and building capacity to identify, contain and respond to a pandemic influenza.The International Partnership on Avian and Pandemic Influenza is committed to protecting human and animal health as well as mitigating the global socioeconomic and security consequences of an influenza pandemic. The partnership seeks to work with all concerned states to limit the spread of H5N1 avian flu and any other highly pathogenic influenza strain by taking all necessary steps to prevent, prepare for, and respond to the growing threat. Partners are concerned about the potential for large-scale outbreaks. As such, participants are committed to the following principles to establish a more coordinated and effective basis for limiting the social, economic and health impacts of avian and pandemic influenza, consistent with national legal authorities and relevant international law and frameworks. Noting that enhanced global cooperation on avian and pandemic influenza will provide a template for global cooperation to address other types of health emergencies, we join together in our commitment to: International cooperation to protect the lives and health of our people; Timely and sustained high-level global political leadership to combat avian and pandemic influenza; Transparency in reporting of influenza cases in humans and in animals caused by strains that have pandemic potential, to increase understanding, preparedness and, especially to ensure rapid and timely response to potential outbreaks; Immediate sharing of epidemiological data and samples with the World Health Organization (WHO) and the international community to detect and characterize the nature and evolution of any outbreaks as quickly as possible, by utilizing, where appropriate, existing networks and mechanisms Rapid reaction to address the first signs of accelerated transmission of H5N1 and other highly pathogenic influenza strains so that appropriate international and national resources can be brought to bear; Prevent and contain an incipient epidemic through capacity building and in-country collaboration with international partners; Work in a manner complementary to and supportive of expanded cooperation with and appropriate support of key multilateral organizations (WHO, Food and Agriculture Organization, World Organization for Animal Health); Timely coordination of bilateral and multilateral resource allocations; dedication of domestic resources (human and financial); improvements in public awareness; and development of economic and trade contingency plans; Increased coordination and harmonization of preparedness, prevention, response and containment activities among nations, complementing domestic and regional preparedness initiatives and encouraging where appropriate the development of strategic regional initiatives; Actions based on the best available science.

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Avian influenza

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2007 Bernard Matthews H5N1 outbreak

The 2007 Bernard Matthews H5N1 outbreak was an occurrence of avian influenza in England caused by the H5N1 subtype of Influenza virus A that began on 30 January 2007. The infection affected poultry at one of Bernard Matthews ' farms in Holton in Suffolk . It was the third instance of H5N1-subtype detected in the United Kingdom and a range of precautions were instituted to prevent spread of the disease including a large cull of turkeys , the imposition of segregation zones, and a disinfection programme for the plant. The cause of the outbreak was not determined. However, it was considered significant that Bernard Matthews regularly transports turkeys and turkey products between the UK and its plant in Hungary , and that the H5N1 strains previously found in Hungary, and those found at Suffolk, were effectively genetically identical.H5N1 is a subtype of the Influenza A virus , the viruses responsible for influenza in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu . HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans is inefficient. Poultry farming practices have changed due to H5N1. The cost of poultry farming has increased, while the cost to consumers has gone down, due to fears from H5N1 driving demand below supply. The outbreak was the third instance of H5N1 detected in the United Kingdom. The first outbreak occurred in October 2005 among exotic birds imported from Taiwan and South America at a privately owned quarantine facility in Essex, England . The second instance involved a dead whooper swan found to have the virus in Cellardyke , Scotland in April 2006. A corresponding incidence on a farm in south-eastern Hungary was confirmed by the European Commission on 25 January 2007. H5N1 is a subtype of the Influenza A virus , the viruses responsible for influenza in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu . HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans is inefficient. Poultry farming practices have changed due to H5N1. The cost of poultry farming has increased, while the cost to consumers has gone down, due to fears from H5N1 driving demand below supply. The outbreak was the third instance of H5N1 detected in the United Kingdom. The first outbreak occurred in October 2005 among exotic birds imported from Taiwan and South America at a privately owned quarantine facility in Essex, England . The second instance involved a dead whooper swan found to have the virus in Cellardyke , Scotland in April 2006. A corresponding incidence on a farm in south-eastern Hungary was confirmed by the European Commission on 25 January 2007. Initial signs of the outbreak occurred on Tuesday, 30 January when 55 turkey poults died and 16 had to be killed because they were sick. At least 185 more died the following day. It was not until 1 February that the deaths were reported to Defra . The farm was sealed off while tests were carried out, on samples taken from the dead birds, at the Veterinary Laboratories Agency in Weybridge , Surrey . Another 1,500 birds died on 2 February. Then on 3 February 2007 the H5N1 causation was confirmed. A 3 km protection zone, 10 km surveillance zone and a restricted zone encompassing 2000 km 2 were set up. Another 159,000 turkeys were slaughtered with the cull being completed on the evening of 5 February. Also on 5 February there was criticism that nearby farmers had not been advised as to the action to be taken. Around 320 workers at the plant were given anti-viral drugs. Although a vet from the site was admitted into hospital, suffering from a 'mild respiratory illness' during the evening of 6 February, it was found not to be bird flu. The plant was thoroughly disinfected, with cleaning complete on 12 February, and permission being given for production to resume. It emerged in a highly critical report from Defra that there was a series of biosecurity failings at the Holton plant, some of which were drawn to the company's attention in the past. These included "gulls were taking turkey waste to roosts on top of the turkey-house 500 m away" and "holes in the turkey houses could have allowed in birds or rodents". Defra minister Jeff Rooker stated in a House of Lords debate on 22 February that the outbreak was "exclusively a Bernard Matthews Holton problem". The Government , on 8 February, admitted that the outbreak may have been caused by semi-processed turkey meat imported directly from Hungary , where the disease is prevalent, despite earlier in the week the Environment Secretary , David Miliband assuring the House of Commons that there was "no Hungarian connection". Bernard Matthews had been importing 38 tons of partly processed turkey meat on a weekly basis from their Saga Foods company, in Sárvár , Hungary, to a processing plant next to the farm. Though Saga Foods lies 165 miles (266 km) from where the recent Hungarian H5N1 outbreak had occurred, a company director admitted it was "possible" that some of the meat could have come from the exclusion zone. In response to this revelation, Whitehall expressed concern over biosecurity and whether any meat may have been distributed for human consumption in Britain. On 9 February 2007 the Hungarian authorities started an investigation to try to establish whether there was a connection between the Suffolk and Hungarian outbreaks. On 11 February the investigation revealed that turkey products were still being transported, in both directions, between the plant and Hungary with EU regulations being cited as the reason why a transport ban could not be imposed. The Hungary link was dismissed by the European Commission on 12 February. Even so, the H5N1 bird flu strains found in Hungary and Britain were shown to be 99.96% genetically identical and, according to an analysis of the viruses by the Veterinary Laboratories Agency in Weybridge , Surrey , were almost certainly linked. A leak from the Government's COBRA emergency committee indicated that the authorities were not aware of the Hungarian connection until an investigator found a Gallfoods delivery wrapper in a Bernard Matthews bin. This raised the possibility that the outbreak was due to a "third party abattoir , Gallfoods in Hungary , just outside the restricted zone". This abattoir might have been a middle man for contaminated poultry farming tools, feed, or product from within the restricted zone, such as a Bernard Matthews owned subsidiary in Hungary. In response to the incident and allegations of a cover-up, Bernard Matthews himself stated on 14 February "I'm sorry – but this has not been of our making. There's been absolutely no cover-up at our end. I've been upset about allegations that we may have withheld information. That is completely untrue." Bernard Matthews was given permission to resume its shipments of poultry between the UK and Hungary from 17 February even though Defra indicated that Hungarian turkey products remained the "most plausible" cause of the outbreak. By 8 February there was a lengthening list of countries that had banned the importation of poultry products from Britain including South Africa, Russia, Japan, and many others but a spokesman for the European Commission condemned the bans as "totally disproportionate" and the British Poultry Council pointed out that exports were less than 9% of the level of domestic sales. Supermarket sales of Bernard Matthews branded turkeys halved after the onset of the outbreak as shoppers sought out alternatives. One of the biggest ongoing surveys of consumer confidence revealed that, by 13 February 2007, Bernard Matthews was the least respected and trusted brand in Britain. Following the outbreak the company confirmed, on 19/02/2007, that 130 workers would be laid off for a period of twenty days due to a drop in product sales. The Transport and General Workers' Union then called for the government to provide compensation to the workers affected. The Transport and General Workers' Union paid out hardship monies from union funds to union members, on top of any state benefits to which the laid-off workers were entitled and a one-off £100 payment from Bernard Matthews. A row broke out on 01/03/2007 when it emerged that the government was paying compensation to the company for the 159 000 culled turkeys while laid-off workers were receiving nothing. At £3.75 each for hens and £3.53 for toms, the payout was then estimated at between £537 000 and £570 000. In the event, though, the actual compensation bill came out at £589,356.89. The crisis cost Bernard Matthews at least £20 m in lost sales and costs.

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Avian influenza

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Operation Dark Winter

Operation Dark Winter was the code name for a senior-level bio-terrorist attack simulation conducted on June 22–23, 2001. It was designed to carry out a mock version of a covert and widespread smallpox attack on the United States. Tara O'Toole and Tom Inglesby of the Johns Hopkins Center for Civilian Biodefense Strategies (CCBS) / Center for Strategic and International Studies (CSIS), and Randy Larsen and Mark DeMier of Analytic Services were the principal designers, authors, and controllers of the Dark Winter project.Dark Winter was focused on evaluating the inadequacies of a national emergency response during the use of a biological weapon against the American populace. The exercise was intended to establish preventive measures and response strategies by increasing governmental and public awareness of the magnitude and potential of such a threat posed by biological weapons. Dark Winter's simulated scenario involved an initial localized smallpox attack on Oklahoma City, Oklahoma , with additional smallpox attack cases in Georgia and Pennsylvania . The simulation was then designed to spiral out of control, and to be an inherently unwinnable scenario. This would create a contingency in which the National Security Council struggles to determine both the origin of the attack as well as deal with containing the spreading virus. By not being able to keep pace with the disease's rate of spread, a new catastrophic contingency emerges in which massive civilian casualties would overwhelm America's emergency response capabilities. The disastrous contingencies that would result in the massive loss of civilian life were used to exploit the weaknesses of the U.S. health care infrastructure and its inability to handle such a threat. The contingencies were also meant to address the widespread panic that would emerge and which would result in mass social breakdown and mob violence. Exploits would also include the many difficulties that the media would face when providing American citizens with the necessary information regarding safety procedures. Discussing the outcome of Dark Winter, Bryan Walsh noted "The timing--just a few months before the 9/11 attack--was eerily prescient, as if the organizers had foreseen how the threat of terrorism, including bioterrorism, would come to consume the U.S. government and public in the years to come." Dark Winter was focused on evaluating the inadequacies of a national emergency response during the use of a biological weapon against the American populace. The exercise was intended to establish preventive measures and response strategies by increasing governmental and public awareness of the magnitude and potential of such a threat posed by biological weapons.Dark Winter's simulated scenario involved an initial localized smallpox attack on Oklahoma City, Oklahoma , with additional smallpox attack cases in Georgia and Pennsylvania . The simulation was then designed to spiral out of control, and to be an inherently unwinnable scenario. This would create a contingency in which the National Security Council struggles to determine both the origin of the attack as well as deal with containing the spreading virus. By not being able to keep pace with the disease's rate of spread, a new catastrophic contingency emerges in which massive civilian casualties would overwhelm America's emergency response capabilities. The disastrous contingencies that would result in the massive loss of civilian life were used to exploit the weaknesses of the U.S. health care infrastructure and its inability to handle such a threat. The contingencies were also meant to address the widespread panic that would emerge and which would result in mass social breakdown and mob violence. Exploits would also include the many difficulties that the media would face when providing American citizens with the necessary information regarding safety procedures. Discussing the outcome of Dark Winter, Bryan Walsh noted "The timing--just a few months before the 9/11 attack--was eerily prescient, as if the organizers had foreseen how the threat of terrorism, including bioterrorism, would come to consume the U.S. government and public in the years to come." According to UPMC's Center for Health Security, Dark Winter outlined several key findings with respect to the United States healthcare system's ability to respond to a localized bioterrorism event: An attack on the United States with biological weapons could threaten vital national security interests. In addition to the possibility of massive civilian casualties, Dark Winter outlined the possible breakdown in essential institutions, resulting in a loss of confidence in government, followed by civil disorder, and a violation of democratic processes by authorities attempting to restore order. Shortages of vaccines and other drugs affected the response available to contain the epidemic, as well as the ability of political leaders to offer reassurance to the American people. This led to great public anxiety and flight by people desperate to get vaccinated, and it had a significant effect on the decisions taken by the political leadership. In addition, Dark Winter revealed that a catastrophic biowarfare event in the United States would lead to considerably reduced U.S. strategic flexibility abroad. Current organizational structures and capabilities are not well suited for the management of a biowarfare attack. Dark Winter revealed that major "fault lines" exist between different levels of government (federal, state, and local), between government and the private sector, among different institutions and agencies, and within the public and private sector. Leaders are unfamiliar with the character of bioterrorist attacks, available policy options, and their consequences. Federal and state priorities may be unclear, differ, or conflict; authorities may be uncertain; and constitutional issues may arise. For example, state leaders wanted control of decisions regarding the imposition of disease-containment measures (e.g., mandatory vs. voluntary isolation and vaccination), the closure of state borders to all traffic and transportation, and when or whether to close airports. Federal officials, on the other hand, argued that such issues were best decided on a national basis to ensure consistency and to give the President maximum control of military and public-safety assets. Leaders in states most affected by smallpox wanted immediate access to smallpox vaccine for all citizens of their states, but the federal government had to balance these requests against military and other national priorities. State leaders were opposed to federalizing the National Guard, which they were relying on to support logistical and public supply needs, while a number of federal leaders argued that the National Guard should be federalized. There is no surge capability in the U.S. healthcare and public health systems, or in the pharmaceutical and vaccine industries. The exercise was designed to simulate a sudden and unexpected biowarfare event for which the United States healthcare system was unprepared. In the absence of sufficient preparation, Dark Winter revealed that the lack of sufficient vaccine or drugs to prevent the spread of disease severely limited management options. Due to the institutionally limited "surge capacity" of the American healthcare system, hospitals quickly became overwhelmed and rendered effectively inoperable by the sudden and continued influx of new cases, exacerbated by patients with common illnesses who feared they might have smallpox, and people who were otherwise healthy but concerned about their possible exposure. The challenges of making correct diagnoses and rationing scarce resources, combined with shortages of health care staff, who were themselves worried about becoming infected or bringing infection home to their families, imposed a huge burden on the health care system. The simulation also noted that while demand was highest in cities and states that had been directly attacked, by the time victims became symptomatic, they were geographically dispersed, with some having traveled far from the original attack site. The simulation also found that without sufficient surge capability, public health agencies' analysis of the scope, source, and progress of the epidemic was greatly impeded, as was their ability to educate and reassure the public, and their capacity to limit casualties and the spread of disease. For example, even after the smallpox attack was recognized, decisionmakers were confronted with many uncertainties and wanted information that was not immediately available. (In fact, they were given more information on locations and numbers of infected people than would likely be available in reality.) Without accurate and timely information, participants found it difficult to quickly identify the locations of the original attacks; to immediately predict the likely size of the epidemic on the basis of initial cases; to know how many people were exposed; to find out how many were hospitalized and where; or to keep track of how many had been vaccinated. Dealing with the media will be a major immediate challenge for all levels of government. Dark Winter revealed that information management and communication (e.g., dealing with the press effectively, communication with citizens, maintaining the information flows necessary for command and control at all institutional levels) will be a critical element in crisis/consequence management. For example, participants worried that it would not be possible to forcibly impose vaccination or travel restrictions on large groups of the population without their general cooperation. To gain that cooperation, the President and other leaders in Dark Winter recognized the importance of persuading their constituents that there was fairness in the distribution of vaccine and other scarce resources, that the disease-containment measures were for the general good of society, that all possible measures were being taken to prevent the further spread of the disease, and that the government remained firmly in control despite the expanding epidemic. Should a contagious bioweapon pathogen be used, containing the spread of disease will present significant ethical, political, cultural, operational, and legal challenges. In Dark Winter, some members advised the imposition of geographic quarantines around affected areas, but the implications of these measures (e.g., interruption of the normal flow of medicines, food and energy supplies, and other critical needs) were not clearly understood at first. In the end, it is not clear whether such draconian measures would have led to a more effective interruption of disease spread. What's more, allocation of scarce resources necessitated some degree of rationing, creating conflict and significant debate between participants representing competing interests.

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Influenza Genome Sequencing Project

The Influenza Genome Sequencing Project ( IGSP ), initiated in early 2004, seeks to investigate influenza evolution by providing a public data set of complete influenza genome sequences from collections of isolates representing diverse species distributions. The project is funded by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), and has been operating out of the NIAID Microbial Sequencing Center at The Institute for Genomic Research (TIGR, which in 2006 became The Venter Institute). Sequence information generated by the project has been continually placed into the public domain through GenBank .In late 2003, David Lipman , Lone Simonsen , Steven Salzberg , and a consortium of other scientists wrote a proposal to begin sequencing large numbers of influenza viruses at The Institute for Genomic Research (TIGR). Prior to this project, only a handful of flu genomes were publicly available. [ citation needed ] Their proposal was approved by the National Institutes of Health (NIH), and would later become the IGSP. New technology development led by Elodie Ghedin began at TIGR later that year, and the first publication describing > 100 influenza genomes appeared in 2005 in the journal Nature The project makes all sequence data publicly available through GenBank , an international, NIH-funded, searchable online database. This research helps to provide international researchers with the information needed to develop new vaccines , therapies and diagnostics, as well as improve understanding of the overall molecular evolution of Influenza and other genetic factors that determine their virulence. [ citation needed ] Such knowledge could not only help mitigate the impact of annual influenza epidemics , but could also improve scientific knowledge of the emergence of pandemic influenza viruses .The project completed its first genomes in March 2005 and has rapidly accelerated since. By mid-2008, over 3000 isolates had been completely sequenced from influenza viruses that are endemic in human ("human flu") avian ("bird flu") and swine ("swine flu") populations, including many strains of H3N2 (human), H1N1 (human), and H5N1 (avian). The project is funded by the National Institute of Allergy and Infectious Diseases (NIAID) which is a component of the NIH, which is an agency of the United States Department of Health and Human Services . The IGSP has expanded to include a growing list of collaborators, who have contributed both expertise and valuable collections of influenza isolates. Key early contributors included Peter Palese of the Mount Sinai School of Medicine in New York, Jill Taylor of the Wadsworth Center at the New York State Department of Health , Lance Jennings of Canterbury Health Laboratories (New Zealand), Jeff Taubenberger of the Armed Forces Institute of Pathology (who later moved to NIH), Richard Slemons of Ohio State University and Rob Webster of St. Jude's Children's Hospital in Memphis, Tennessee. In 2006 the project was joined by Ilaria Capua of the Istituto Zooprofilattico Sperimentale delle Venezie (in Italy), who contributed a valuable collection of avian flu isolates (including multiple H5N1 strains). Some of these avian isolates were described in a publication in Emerging Infectious Diseases in 2007. Nancy Cox from the Centers for Disease Control and Prevention (CDC) and Robert Couch from Baylor College of Medicine also joined the project in 2006, contributing over 150 influenza B isolates. The project began prospective studies of the 2007 influenza season with collaborators Florence Bourgeois and Kenneth Mandl of Children's Hospital Boston and the Harvard School of Public Health and Laurel Edelman of Surveillance Data Inc. [ citation needed ]

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Veterinary virology

Veterinary virology is the study of viruses in non-human animals . It is an important branch of veterinary medicine .Rhabdoviruses are a diverse family of single stranded, negative sense RNA viruses that infect a wide range of hosts, from plants and insects, to fish and mammals. The Rhaboviridae family consists of six genera , two of which, cytorhabdoviruses and nucleorhabdoviruses, only infect plants. Novirhabdoviruses infect fish, and vesiculovirus, lyssavirus and ephemerovirus infect mammals, fish and invertebrates. The family includes pathogens such as rabies virus, vesicular stomatitis virus and potato yellow dwarf virus that are of public health, veterinary, and agricultural significance. Foot-and-mouth disease virus (FMDV) is a member of the Aphthovirus genus in the Picornaviridae family and is the cause of foot-and-mouth disease in pigs, cattle, sheep and goats. It is a non-enveloped, positive strand, RNA virus. FMDV is a highly contagious virus. It enters the body through inhalation. Pestiviruses have a single stranded, positive-sense RNA genomes. They cause Classical swine fever (CSF) and Bovine viral diarrhea (BVD). Mucosal disease is a distinct, chronic persistent infection, whereas BVD is an acute infection. Arteriviruses are small, enveloped, animal viruses with an icosahedral core containing a positive-sense RNA genome. The family includes equine arteritis virus (EAV), porcine reproductive and respiratory syndrome virus (PRRSV), lactate dehydrogenase elevating virus (LDV) of mice and simian haemorrhagic fever virus (SHFV). Coronaviruses are enveloped viruses with a positive-sense RNA genome and with a nucleocapsid of helical symmetry. They infect the upper respiratory and gastrointestinal tract of mammals and birds. They are the cause of a wide range of diseases in cats, dog, pigs, rodents, cattle and humans. Transmission is by the faecal-oral route. Torovirus is a genus of viruses within the family Coronaviridae , subfamily Torovirinae that primarily infect vertebrates and include Berne virus of horses and Breda virus of cattle. They cause gastroenteritis in mammals, including humans but rarely. Influenza is caused by RNA viruses of the family Orthomyxoviridae and affects birds and mammals. Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from this reservoir to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics . Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from this reservoir to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics . Bluetongue virus (BTV), a member of Orbivirus genus within the Reoviridae family causes serious disease in livestock (sheep, goat, cattle). It is non-enveloped, double-stranded RNA virus. The genome is segmented. Circoviruses are small single-stranded DNA viruses. There are two genera: gyrovirus, with one species called chicken anemia virus; and circovirus, which includes porcine circovirus types 1 and 2, psittacine beak and feather disease virus, pigeon circovirus, canary circovirus, goose circovirus. Herpesviruses are ubiquitous pathogens infecting a variety of animals, including humans. Hosts include many economically important species such as abalone, oysters, salmon, poultry ( avian infectious laryngotracheitis , Marek's disease ), cattle ( bovine malignant catarrhal fever ), dogs, goats, horses, cats ( feline viral rhinotracheitis ), and pigs ( pseudorabies ). Infections may be severe and may result in fatalities or reduced productivity. Therefore, outbreaks of herpesviruses in livestock cause significant financial losses and are an important area of study in veterinary virology.African swine fever virus (ASFV) is a large double-stranded DNA virus which replicates in the cytoplasm of infected cells and is the only member of the Asfarviridae family. The virus causes a lethal haemorraghic disease in domestic pigs. Some strains can cause death of animals within as little as a week after infection. In other species, the virus causes no obvious disease. ASFV is endemic to sub-Saharan Africa and exists in the wild through a cycle of infection between ticks and wild pigs, bushpigs and warthogs. Retroviruses are established pathogens of veterinary importance. They are generally a cause of cancer or immune deficiency. Flaviviruses constitute a family of linear, single-stranded RNA(+) viruses. Flaviviruses include the West Nile virus , dengue virus , Tick-borne Encephalitis Virus, Yellow Fever Virus, and several other viruses. Many flavivirus species can replicate in both mammalian and insect cells. Most flaviviruses are arthropod borne and multiply in both vertebrates and arthropods. The viruses in this family that are of veterinary importance include Japanese encephalitis virus , St. Louis encephalitis virus , West Nile virus , Israel turkey meningoencephalomyelitis virus , Sitiawan virus , Wesselsbron virus , yellow fever virus and the tick-borne flaviviruses e.g. louping ill virus . Paramyxoviruses are a diverse family of non-segmented negative strand RNA viruses that include many highly pathogenic viruses affecting humans, animals, and birds. These include canine distemper virus ( dogs ), phocine distemper virus ( seals ), cetacean morbillivirus ( dolphins and porpoises ) Newcastle disease virus ( birds ) and rinderpest virus ( cattle ). Some paramyxoviruses such as the henipaviruses are zoonotic pathogens, occurring primarily in an animal hosts, but also able to infect humans. Parvoviruses are linear, non-segmented single-stranded DNA viruses , with an average genome size of 5000 nucleotides. They are classified as group II viruses in Baltimore classification of viruses. Parvoviruses are among the smallest viruses (hence the name, from Latin parvus meaning small ) and are 18–28 nm in diameter. Parvoviruses can cause disease in some animals , including starfish and humans. Because the viruses require actively dividing cells to replicate, the type of tissue infected varies with the age of the animal. The gastrointestinal tract and lymphatic system can be affected at any age, leading to vomiting, diarrhea and immunosuppression but cerebellar hypoplasia is only seen in cats that were infected in the womb or at less than two weeks of age, and disease of the myocardium is seen in puppies infected between the ages of three and eight weeks.

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Siti Fadilah Supari

Siti Fadilah Supari (born 6 November 1949 in Surakarta , Central Java ), is a cardiology research specialist, a former health minister of Indonesia. She gained global notoriety in 2007 when she took on the World Health Organization 's practice of sharing avian influenza virus samples. Supari was appointed Minister of Health by President Susilo Bambang Yudhoyono on 20 August 2004. She served until 22 October 2009 when she was succeeded by Endang Rahayu Sedyaningsih , an epidemiologist and close advisor in her team. On 3 August 2006, Supari made the unprecedented move by announcing that the Indonesian government will make genomic data on bird flu viruses accessible to anyone. Supari said, opening up global access could be the key to unlocking such vital information as to the origin of the virus, how it causes disease, how it is mutating, the sources of infection, and how to prevent or cure the virus. "But in future cooperation on bird flu with other countries, the delivery of specimens should be regulated under Material Transfer Agreement documents as is commonly practised in scientific cooperation," Supari added. The Economist wrote, Supari started a revolution that could yet save the world from the ravages of a pandemic disease . That is because Indonesia's health minister has chosen a weapon that may prove more useful than today's best vaccines in tackling such emerging threats as avian flu: transparency . It was unclear at the time what prompted Supari to share data, given the widespread reluctance of countries affected by the H5N1 virus to share their data, out of fear such disclosure could trigger economic sanctions. Just days before, an editorial published in Nature highlighted this problem with China's practice of belatedly publishing details of a case that tested positive for the virulent H5N1 strain in 2003 — contradicting the government's official line that none had occurred before November 2005. Although not mentioning Supari by name, the editorial also addressed a confirmation by the World Health Organization (WHO) that a cluster of eight cases in an extended family in Northern Sumatra was the first unequivocal occurrence of limited human-to-human transmission of the H5N1 virus. On 22 August 2006, two weeks after Supari made her announcement, Nancy Cox , the director of the influenza division at the US Centers for Disease Control and Prevention (CDC) communicated in a press release that following Indonesia's announcement, it too made genomic data on bird flu viruses publicly accessible. The following day a correspondence letter appeared in Nature shedding light on what had triggered the sudden shift in Supari's stance and that of the CDC . The scientific community had just been introduced to Peter Bogner , the new driving force in the virus sharing debate. Supari would later describe in her book an affinity for Peter Bogner, his plea to her government to share its bird flu virus data and his concern when she annoyed the US administration at times. Supari wrote, "he told me indirectly my speech had been too sharp," or "Peter Bogner has the capability to change the world's opinions." A former broadcast executive at Time Warner , he was not only familiar with intellectual property issues, but more importantly, he was friendly with Supari's government following his role in the 2004 Indian Ocean earthquake and tsunami relief efforts. He would turn out to be the mastermind behind the GISAID initiative, a mechanism devised and financed almost exclusively by him. When Supari attended the 61st World Health Assembly on 16 May 2008, the day GISAID's database was launched, Supari made available genetic H5N1 data alongside other countries like China and Russia. Within four months, this publicly accessible resource offered the world's most comprehensive collection of influenza data. Claiming Western governments could be developing viruses for dissemination in the developing world with the goal of generating business for pharmaceutical companies, Supari refused WHO researchers access to Indonesia's H5N1 bird flu virus samples in 2006. Indonesia resumed sending some H5N1 samples to WHO after a new agreement that developing nations would get access to vaccines. During a press conference on 28 April 2009, Supari reassured the public over the government's response to the swine flu threat and responded to a question on the origin of the H1N1 virus and whether it could have been man-made. Supari stated she was not sure whether the virus was genetically engineered, but it is a possibility. Several news outlets, among them Bloomberg News and the Times of India , reported about an investigation by the WHO into a claim by Australian researchers that the swine flu virus circling the globe may have been created as a result of human error. Australian virologists Adrian Gibbs, John Armstrong and Jean Downie suggested in a paper published in the Virology Journal , the new H1N1 strain , may be the product of three strains from three continents that swapped genes in a lab or a vaccine-making plant, suggesting its origin could be more simply explained by human involvement than a coincidence of nature. On 12 May 2009, Supari expressed her dissatisfaction of seeing many foreign medical students in Indonesia. She asked Universitas Padjadjaran Rector, Bandung to cut down foreign student intake in phases especially from Malaysia while visiting Cicendo Eyes Hospital, Bandung. Supari was instrumental in the termination of the United States Naval Medical Research Unit Two presence in Jakarta, and NAMRU-2 departed Indonesia in 2010. [ citation needed ]On 3 August 2006, Supari made the unprecedented move by announcing that the Indonesian government will make genomic data on bird flu viruses accessible to anyone. Supari said, opening up global access could be the key to unlocking such vital information as to the origin of the virus, how it causes disease, how it is mutating, the sources of infection, and how to prevent or cure the virus. "But in future cooperation on bird flu with other countries, the delivery of specimens should be regulated under Material Transfer Agreement documents as is commonly practised in scientific cooperation," Supari added. The Economist wrote, Supari started a revolution that could yet save the world from the ravages of a pandemic disease . That is because Indonesia's health minister has chosen a weapon that may prove more useful than today's best vaccines in tackling such emerging threats as avian flu: transparency . It was unclear at the time what prompted Supari to share data, given the widespread reluctance of countries affected by the H5N1 virus to share their data, out of fear such disclosure could trigger economic sanctions. Just days before, an editorial published in Nature highlighted this problem with China's practice of belatedly publishing details of a case that tested positive for the virulent H5N1 strain in 2003 — contradicting the government's official line that none had occurred before November 2005. Although not mentioning Supari by name, the editorial also addressed a confirmation by the World Health Organization (WHO) that a cluster of eight cases in an extended family in Northern Sumatra was the first unequivocal occurrence of limited human-to-human transmission of the H5N1 virus. On 22 August 2006, two weeks after Supari made her announcement, Nancy Cox , the director of the influenza division at the US Centers for Disease Control and Prevention (CDC) communicated in a press release that following Indonesia's announcement, it too made genomic data on bird flu viruses publicly accessible. The following day a correspondence letter appeared in Nature shedding light on what had triggered the sudden shift in Supari's stance and that of the CDC . The scientific community had just been introduced to Peter Bogner , the new driving force in the virus sharing debate. Supari would later describe in her book an affinity for Peter Bogner, his plea to her government to share its bird flu virus data and his concern when she annoyed the US administration at times. Supari wrote, "he told me indirectly my speech had been too sharp," or "Peter Bogner has the capability to change the world's opinions." A former broadcast executive at Time Warner , he was not only familiar with intellectual property issues, but more importantly, he was friendly with Supari's government following his role in the 2004 Indian Ocean earthquake and tsunami relief efforts. He would turn out to be the mastermind behind the GISAID initiative, a mechanism devised and financed almost exclusively by him. When Supari attended the 61st World Health Assembly on 16 May 2008, the day GISAID's database was launched, Supari made available genetic H5N1 data alongside other countries like China and Russia. Within four months, this publicly accessible resource offered the world's most comprehensive collection of influenza data. Claiming Western governments could be developing viruses for dissemination in the developing world with the goal of generating business for pharmaceutical companies, Supari refused WHO researchers access to Indonesia's H5N1 bird flu virus samples in 2006. Indonesia resumed sending some H5N1 samples to WHO after a new agreement that developing nations would get access to vaccines. During a press conference on 28 April 2009, Supari reassured the public over the government's response to the swine flu threat and responded to a question on the origin of the H1N1 virus and whether it could have been man-made. Supari stated she was not sure whether the virus was genetically engineered, but it is a possibility. Several news outlets, among them Bloomberg News and the Times of India , reported about an investigation by the WHO into a claim by Australian researchers that the swine flu virus circling the globe may have been created as a result of human error. Australian virologists Adrian Gibbs, John Armstrong and Jean Downie suggested in a paper published in the Virology Journal , the new H1N1 strain , may be the product of three strains from three continents that swapped genes in a lab or a vaccine-making plant, suggesting its origin could be more simply explained by human involvement than a coincidence of nature. On 12 May 2009, Supari expressed her dissatisfaction of seeing many foreign medical students in Indonesia. She asked Universitas Padjadjaran Rector, Bandung to cut down foreign student intake in phases especially from Malaysia while visiting Cicendo Eyes Hospital, Bandung. Supari was instrumental in the termination of the United States Naval Medical Research Unit Two presence in Jakarta, and NAMRU-2 departed Indonesia in 2010. [ citation needed ]Supari is a cardiology research specialist based in Jakarta . Supari was married for 36 years to Muhammad Supari until his death in March 2009. On 16 June 2017, Supari was convicted of corruption and sentenced to four years in jail. The Jakarta Corruption Court found she had accepted bribes related to the procurement of medical equipment for the Health Ministry's crisis centre in 2005. She was fined IDR 200 million (US$15,042), although her actions had caused IDR 6.15 billion in state losses. The court ruled she had abused her authority as a minister by accepting bribes of IDR 3.2 billion from two directors of PT Graha Ismaya in the form of traveller's checks. She was ordered to return IDR 550 million to the state after previously returning IDR 1.35 billion. Her former subordinate Rustam Pakaya was also sentenced to four years in jail over a 2007 procurement corruption case that caused IDR 21.3 billion in state losses.

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Chen Hualan

Chen Hualan ( simplified Chinese : é™ˆåŒ–å ° ; traditional Chinese : 陳化蘭 ; pinyin : Chén Huà lán ; born March 1969) is a Chinese veterinary virologist best known for researching animal epidemic diseases. She is a member of the World Organisation for Animal Health (OIE) and a member of the Food and Agriculture Organization Corporate Statistical Database (FAOSTAT). She is now a researcher and PhD Supervisor at Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences . She has been listed among the "Ten Scientific Figures of the Year" by Nature in 2013. She won the L'Oréal-UNESCO Awards for Women in Science in 2016, and was elected to the Chinese Academy of Sciences in 2017. Chen was born in Jingyuan County , Baiyin , Gansu province in 1969. In 1987, she was admitted to the Department of Veterinary Medicine of Gansu Agricultural University. In 1991, after receiving a bachelor's degree, she continued to major in veterinary pathology in the Department of Veterinary Medicine of Gansu Agricultural University and studied as a graduate student. In 1994, after graduating with a master's degree, she was admitted to the Graduate School of the Chinese Academy of Agricultural Sciences. In 1997, she obtained a doctorate degree in infectious disease and preventive veterinary medicine, and then worked as an assistant researcher at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. In 1999, she went to the Influenza Sub-center of the Centers for Disease Control of the United States for post-doctoral work and collaborative research on bird flu. In 2002, she returned to China and served as a researcher at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, and successively served as the director of the Key Laboratory of Animal Influenza of the Ministry of Agriculture and the director of the National Avian Influenza Reference Laboratory. On November 9, 2005, she won the 2nd China Young Women Scientist Award. In 2006, she won the China Youth May 4 Medal. In 2008, she served as the director of the Avian Influenza Reference Laboratory of the World Organization for Animal Health. In 2008, she was awarded the National Science Fund for Distinguished Young Scholars. In 2009, joined the Jiu San Society. In October 2015, she was awarded the "World Outstanding Female Scientist Achievement Award" by UNESCO-L'Oréal, and is the fifth Chinese to receive this award. In the same year, she was named one of the "Global Highly Cited Scientists" by Thomson Reuters. In June 2016, she won the National Outstanding Science and Technology Talent Award and the China Outstanding Young Science and Technology Talent Award. In November 2017, she was elected an academician of the Chinese Academy of Sciences. In March 2018, she served as a member of the Agricultural and Rural Committee of the 13th National Committee of the Chinese People's Political Consultative Conference. In November 2018, Vice Chairman (concurrently) of the All-China Women's Federation, a researcher at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, the director of the Key Laboratory of Animal Influenza of the Ministry of Agriculture and Rural Affairs, and an academician of the Chinese Academy of Sciences. Member of the 12th and 13th National Committee of the Chinese People's Political Consultative Conference. On the afternoon of November 1, 2018, the 12th Executive Committee of the All-China Women's Federation held its first plenary meeting. Chen Hualan was elected as the vice chairman of the All-China Women's Federation.Chen is married and has a son.Research Summary Chen Hualan presided over the National Avian Influenza Reference Laboratory and systematically carried out the epidemiological monitoring and research work of avian influenza in China, and achieved a series of significant progress and creative research results, and initially clarified the molecular genetics, antigenic variation and pathogenicity of the avian influenza virus. The law of evolution provides a comprehensive scientific basis for the early warning and forecasting of the epidemic, prevention and control strategies, the development and use of diagnostic reagents and vaccines. During the prevention and control of avian influenza, the rapid and accurate diagnosis of a large number of samples from all over the country played a key role in the timely and effective control of the epidemic. It has made a significant contribution to the control of the bird flu epidemic. Leading the National Avian Influenza Reference Laboratory has made a series of significant progress and creative research results in the epidemiology, diagnostic technology, new vaccine development, molecular evolution and molecular pathogenic mechanism of animal influenza, especially avian influenza, and successfully developed H5 The subtype inactivated avian influenza vaccine and the new "avian influenza and Newcastle disease recombinant dual live vaccine" represent the international advanced level and development trend of the avian influenza vaccine development. After the promotion and application, it has greatly improved the prevention and control of poultry in China and the world. The ability of influenza has very important socio-economic and public health significance. In April 2013, Chen Hualan and her scientific research team discovered that the new H7N9 influenza virus that causes human infection in China is highly homologous to the H7N9 avian influenza virus that existed in the live poultry market during the same period. It is the first internationally from the perspective of etiology. The source of the new H7N9 influenza virus was revealed, which provided an important basis for the scientific prevention and control of H7N9 avian influenza in China. In May, they discovered that the H5N1 virus could indeed reassort with the human influenza virus to obtain the ability to transmit efficiently through the air between mammals, thus having the potential to cause a human pandemic, revealing the H5N1 virus from a new perspective. A real threat to global public health. In July, she and researchers found that the H7N9 virus is not pathogenic to poultry, but after the virus invades the human body and mutates, its pathogenicity and horizontal transmission ability to mammals are significantly enhanced, thus revealing the existence of H7N9 virus. The risk of a pandemic among adults. These results have been published in the English version of "Science Bulletin" and "Science (SCIENCE)" magazine. On November 20, 2019, the Chinese Academy of Agricultural Sciences released 10 basic scientific research results that can fully represent the frontier research level of my country's agricultural science and technology in 2018 and have made major breakthroughs, including: the rapid development of the H7N9 highly pathogenic avian influenza virus Evolution and its successful prevention and control. The research was led by the team of Academician Chen Hualan from the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences. Through large-scale monitoring of poultry avian influenza viruses, the H7N9 highly pathogenic avian influenza viruses were systematically studied and successfully developed H5 and H7 bivalents. The avian influenza inactivated vaccine, monitoring results showed that the vaccine effectively blocked the H7N9 virus from spreading in poultry, and it also achieved "immediate results" in blocking human infection with the H7N9 virus. Project commitment & achievement reward Since 1994, Chen Hualan has been engaged in basic research and applied research related to avian influenza and swine influenza, and has presided over more than 20 scientific research projects such as national "key research", "863", "973", and the National Natural Science Foundation of China. Journal Papers & Patented Inventions As of 2014, Chen Hualan has published more than 50 SCI papers related to avian influenza research in important international academic journals; he has obtained 6 new veterinary drug certificates for avian influenza vaccines, of which 3 are genetic engineering vaccines; and 7 national invention patents have been obtained Representative articles 1. Yanbing Li, Liling Liu, Yi Zhang, Zhenhua Duan, Guobin Tian, Xianying Zeng, Jianzhong Shi, Licheng Zhang, Hualan Chen*. New lineage of H5N1 influenza virus detected in wild birds in Qinghai, western China. Emerging Infectious Disease, 2010, in press. 2. Ying Chen, Gongxun Zhong, Guojun Wang, Guohua Deng, Yanbing Li, Jianzhong Shi, Zhuo Zhang, Yuntao Guan, Yongping Jiang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen*. Dogs are highly susceptible to H5N1 avian influenza virus. Virology. 2010, 405, 15-19, on-line, June 25. 3. Lihong Tao, Jinying Ge, Xijun Wang, Hongyue Zhai, Tao Hua, Bolin Zhao, Dongni Kong, Chinglai Yang, Hualan Chen*, and Zhigao Bu*. Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation. Journal of Virology. 2010, 84 (17), 8926-8936. on-line, June 10 4. Yanbing Li, Jianzhong Shi, Gongxun Zhong, Guohua Deng, Guobin Tian, Jinying Ge, Xianying Zeng, Jiasheng Song, Dongming Zhao, Liling Liu, Yongping Jiang, Yuntao Guan, Zhigao Bu, Hualan Chen*. Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry and humans in China from 2004 to 2009. Journal of Virology. 2010, 84(17), 8389-8379. On-line, June 10. 5. Yujie Tang, Gongxun Zhong, Lianhui Zhu, Xing Liu, Yufei Shan, Huapeng Feng, Zhigao Bu, Hualan Chen*, and Chen Wang. Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein. Journal of Immunology, 2010, 184, 5777-5790 6. Bo Wah Leung, Hualan Chen, George G. Brownlee. Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity. Virology, 2010, 401:96-106. 7. Yuwei Gao, Ying Zhang, Kyoko Shinya, Guohua Deng, Yongping Jiang, Zejun Li, Yutao Guan, Guobin Tian, Yanbing Li, Jianzhong Shi, Liling Liu, Xianying Zeng, Zhigao Bu, Xianzhu Xia, Yoshihiro Kawaoka, Hualan Chen*. Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host. PLoS Pathogens, 2009, 5(12): e1000709. 8. Yongping Jiang, Hongbo Zhang, Guojun Wang, Pingjing Zhang, Guobin Tian, Zhigao Bu, and Hualan Chen*. Protective Efficacy of H7 Subtype Avian Influenza DNA Vaccine. Avian Disease, 2010, 54(S1), 294-296. 9. Jinying Ge, Guobin Tian, Xianying Zeng, Yongping Jiang, Hualan Chen and Zhigao Bu*. Generation and Evaluation of a Newcastle Disease Virus-Based H9 Avian Influenza Live Vaccine. Avian Disease, 2010, 54(S1), 290-293. 10. Guobin Tian, Xianying Zeng, Yanbing Li, Jianzhong Shi, Hualan Chen*. Protective Efficacy of the H5 Inactivated Vaccine against Different Highly Pathogenic H5N1 Avian Influenza Viruses Isolated in China and Vietnam. Avian Disease, 2010, 54(S1), 287-289. 11. Neumann G, Chen H, Gao GF, Shu Y, Kawaoka Y. H5N1 influenza viruses: outbreaks and biological properties. Cell Research, 2010, 20(1):51-61 12. Qimeng Tao, Xiurong Wang, Hongmei Bao, Jianan Wu, Lin Shi, Yanbing Li, Chuanling Qiao, Yakovlevich SA, Mikhaylovna PN, Hualan Chen. Detection and differentiation of four poultry diseases using asymmetric reverse transcription polymerase chain reaction in combination with oligonucleotide microarrays. J Vet Diagn Invest. 2009;21(5):623-632 13. Chuantian Xu, Qiyun Zhu, Huanliang Yang, Xiumei Zhang, Chuanling Qiao, Yan Chen, Xiaoguang Xin, Hualan Chen*. Two genotypes of H1N2 influenza viruses appeared among pigs in China. Journal of Clinical Virology. 2009, 46: 192-195. 14. Hualan Chen, Zhigao Bu. Development and application of avian influenza vaccines in China. Current Topics in Microbiology and Immunology. 2009;333:153-62 (Review) 15. Hualan Chen. Avian influenza vaccination: the experience in China. Rev Sci Tech. 2009, 28(1): 267-74 (Review) 16. Jiyong Zhou, Wenbo Sun, Junhua Wang, Junqing Guo, Wei Yin, Nanping Wu, Lanjuan Li, Yan Yan, Ming Liao, Yu Huang, Kaijian Luo, Xuetao Jiang, Hualan Chen. Characterization of the H5N1 Highly Pathogenic Avian Influenza Virus derived from Wild Pikas in China. J Virol. 2009, 83: 8957-8964 17. Hualan Chen. H5N1 avian influenza in China. Sci China C Life Sci. 2009, 52(5):419-27. (Review) 18. Szretter KJ, Gangappa S, Belser JA, Zeng H, Chen H, Matsuoka Y, Sambhara S, Swayne DE, Tumpey TM, Katz JM. Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J Virol. 2009 83(11): 5825-34 19. Kashiwagi T, Leung BW, Deng T, Chen H, Brownlee GG.. The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS ONE. 2009; 4(5):e5473. 20. Shufang Fan, Yuwei Gao, Kyoko Shinya, Chris K-F. Li, Yanbing Li, Jianzhong Shi, Yongping Jiang, Yongbing Suo, Tiegang Tong, Gongxun Zhong, Jiasheng Song, Ying Zhang, Guobin Tian, Yuntao Guan, Xiaoning Xu, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathogens, 2009, 5(5), e1000409 21. Chuanling Qiao, Yongping Jiang, Guobin Tian, Xiurong Wang, Chengjun Li, Xiaoguang Xin, Hualan Chen, Kangzhen Yu. Recombinant Fowlpox Virus Vector-based Vaccine Completely Protects Chickens from H5N1 Avian Influenza Virus. Antiviral Research, 2009, 81(3):234-8 22. Shufang Fan, Guohua Deng, Jiasheng Song, Guobin Tian, Yongbing Suo, Yongping Jiang, Yuntao Guan, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology, 2009, 384: 29-32 23. Murakami S, Horimoto T, Mai le Q, Nidom CA, Chen H, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-Horimoto K, Shimojima M, Iwata A, Kawaoka Y. Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. Journal of Virology, 2008, 82: 10502-9 24. Beibei Jia, Jianzhong Shi, Yanbing Li, Kyoko Shinya, Yukiko Muramoto, Xianying Zeng, Guobin Tian, Yoshihiro Kawaoka, Hualan Chen. Pathogenicity of Chinese H5N1 Highly Pathogenic Avian Influenza Viruses in Pigeons. Archives of Virology, 2008, 153: 1821-1826 25. Chengjun Li, Jihui Ping, Bo Jing, Guohua Deng, Yongping Jiang, Yanbing Li, Guobin Tian, Kangzhen Yu, Zhigao Bu, Hualan Chen. H5N1 influenza marker vaccine for serological differentiation between vaccinated and infected chickens. Biochemical and Biophysical Research Communications, 2008, 372(2): 293-7 26. Kiyoko Iwatsuki-Horimoto, Yasuko Hatta, Masato Hatta, Yukiko Muramoto, Hualan Chen, Yoshihiro Kawaoka, Taisuke Horimoto. Limited compatibility between the RNA polymerase components of influenza virus type A and B. Virus Research, 2008, 135(1): 161-5 27. Jihui Ping, Chengjun Li, Guohua Deng, Yongping Jiang, Guobin Tian, Shuxia Zhang, Zhigao Bu and Hualan Chen. Single-amino-acid mutation in the HA alters the recognition of H9N2 influenza virus by a monoclonal antibody. Biochemical and Biophysical Research Communications, 2008, 371(1): 168-371 28. Peirong Jiao, Guobin Tian, Yanbing Li, Guohua Deng, Yongping Jiang, Chang Liu, Weilong Liu, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A single amino acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. Journal of Virology, 2008, 82 (3): 1146–1154. Comment in Journal of Virology: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses. Journal of Virology, 2008, 82 (3): 1065 Comment in Microbe: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses. 29. Qiyun Zhu, Huangliang Yang, Weiye Chen, Wenyan Cao, Gongxun Zhong, Peirong Jiao, Guohua Deng, Kangzhen Yu, Chinglai Yang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A naturally occurring deletion in its NS gene contributes to attenuation of an H5N1 swine influenza virus in chickens. Journal of Virology, 2008, 82 (1):220–228. 30. Hualan Chen, Rick Bright, Kanta Subbarao, Catherine Smith, Nancy Cox, Jacqueline M. Katz, and Yumiko Matsuoka. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Research, 2007, 128(1-2):159-63. 31. Yongping Jiang, Kangzhen Yu, Hongbo Zhang, Pingjing Zhang, Chenjun Li, Guobin Tian, Yanbing Li, Xijun Wang, Zhigao Bu, Hualan Chen. Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon optimized HA gene in a pCAGG plasmid vector. Antiviral Research, 2007, 75: 234-241. 32. Jinying Ge, Guohua Deng, Zhiyuan Wen, Guobing Tian, Yong Wang, Jianzhong Shi, Xijun Wang, Yanbing Li, Sen Hu, Yongping Jiang, Chinglai Yang, Kangzhen Yu, Zhigao Bu, Hualan Chen. Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. Journal of Virology, 2007, 81, 150-158. 33. Chuanling Qiao, Guobin Tian, Yongping Jiang, Yanbing Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. Vaccines Developed for H5 Highly Pathogenic Avian Influenza in China. Ann. N.Y. Acad. Sci. 2006, 1081: 182–192 34. Zejun Li, Yongping Jiang, Peirong Jiao, Aiqin Wang, Fengju Zhao, Guobin Tian, Xijun Wang, Kangzhen Yu, Zhigao Bu and Hualan Chen. The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. Journal of Virology, 2006, 80:11115-11123. 35. Taronna R. Maines, Li-Mei Chen, Yumiko Matsuoka, Hualan Chen, Thomas Rowe, Juan Ortin, Ana Falco'n, Nguyen Tran Hien, Le Quynh Mai, Endang R. Sedyaningsih, Syahrial Harun, Terrence M. Tumpey, Ruben O. Donis, Nancy J. Cox, Kanta Subbarao, and Jacqueline M. Katz. Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model. Proc. Natl. Acad. Sci. USA, 2006, 103(32): 12121-12126 36. Hualan Chen, Yanbing Li, Zejun Li, Jianzhong Shi, Kyoko Shinya, Guohua Deng, Qiaoling Qi, Guobin Tian, Shufang Fan, Haidan Zhao, Yingxiang Sun, Yoshihiro Kawaoka. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. Journal of Virology, 2006, 80(12):5976-83. 37. Yanbing Li, Chengjun Li, Liling Liu, Hongwei Wang, Chuanbin Wang, Guobing Tian, Robert. G. Webster, Kangzhen Yu, Hualan Chen. Characterization of an avian influenza virus of subtype H7N2 isolated from chickens in northern China. Virus Genes, 2006, 33:117-122 38. Yanbing Li, Zhixiong Lin, Jianzhong Shi, Qiaoling Qi, Guohua Deng, Zejun Li, Xiurong Wang, Guobin Tian, Hualan Chen. Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl. Archives of Virology. 2006, 151: 1615-1624 39. Yu H, Shu Y, Hu S, Zhang H, Gao Z, Chen H, Dong J, Xu C, Zhang Y, Xiang N, Wang M, Guo Y, Cox N, Lim W, Li D, Wang Y, Yang W. The first confirmed human case of avian influenza A (H5N1) in Chinese mainland. Lancet. 2006, 7: 367(9504):84. 40. Zejun Li, Hualan Chen, Peirong Jiao, Guohua Deng, Guobin Tian, Yanbing Li, Erich Hoffmann, Robert G. Webster, Yumiko Matsuoka, Kangzhen Yu. Molecular basis associated with replication of duck H5N1 influenza viruses in a mammalian mouse model. Journal of Virology, 2005, 79: 12058–12064 41. Guobin Tian, Suhua Zhang, Yanbing Li, Zhigao Bu, Peihong Liu, Jinping Zhou, Chengjun Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. Protective efficacy in chickens, geese and ducks of an H5N1 inactivated vaccine developed by reverse genetics. Virology, 2005, 341: 153 – 162 42. Chengjun Li, Kangzhen Yu, Guobin Tian, Dandan Yu, Liling Liu, Bo Jing, Jihui Ping, and Hualan Chen. Evolution of H9N2 influenza viruses from domestic poultry in Chinese mainland. Virology, 2005, 340: 70 – 83 43. K. M. Sturm-Ramirez, D. J. Hulse-Post, E. A. Govorkova, J. Humberd, P. Seiler, P. Puthavathana, C. Buranathai, T. D. Nguyen, A. Chaisingh, H. T. Long, T. S. P. Naipospos, H. Chen, T. M. Ellis, Y. Guan, J. S. M. Peiris, and R. G. Webster. Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia. Journal of Virology, 2005, 79(17): 11269-11279 44. D. J. Hulse-Post, K. M. Sturm-Ramirez, J. Humberd, P. Seiler, E. A. Govorkova, S. Krauss, C. Scholtissek, P. Puthavathana, C. Buranathai, T. D. Nguyen, H. T. Long, T. S. P. Naipospos, H. Chen, T. M. Ellis, Y. Guan, J. S. M. Peiris and R. G. Webster. Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc. Natl. Acad. Sci. USA, 2005, 102: 10682-10687 45. H. Chen,G. Deng,Z. Li,G. Tian,Y. Li,P. Jiao, L. Zhang, Z. Liu, R. G. Webster, K. Yu. The evolution of H5N1 influenza viruses in ducks in Southern China. Proc. Natl. Acad. Sci. USA, 2004, 101(28): 10452-10457 Comments in Nature: Increasing virulence of bird flu threatens mammals. Nature, 2004, 431, July 1, 4. 46. Hualan Chen, Yumiko Matsuoka, David Swayne, Qi Chen, Nancy Cox, Brain R. Murphy and Kanta Subbarao. Generation and Characterization of an H9N2 Cold-Adapted Reassortant as a Vaccine Candidate, Avian Diseases 2003, 47, 1127-1130 47. Yumiko Matsuoka, Hualan Chen, David Swayne, Safety Evaluation in Chickens of Candidate Human Vaccines against Potential Pandemic Strains of Influenza Avian Diseases, 2003, 47, 926-930 48. Hualan Chen, Yumiko Matsuoka, David Swayne, Qi Chen, Nancy Cox, Brain R. Murphy and Kanta Subbarao. Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza vaccine candidate. Vaccine, 2003, 21(27-28): 4430-4436 49. Hualan Chen, Kanta Subbarao, David Swayne, Qi Chen, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka, Generation and evaluation of a high-growth reassortant H9N2 influenza A virus as a pandemic vaccine candidate. Vaccine 2003, 21(17): 1974-1979 50. Kanta Subbarao, Hualan Chen, David Swayne, Louise Mingay, Ervin Fodor, George Brownlee, Xiyan Xu, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology, 2003, 1.Jan 5, 305(1): 192-200

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Avian influenza

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Flu (disambiguation)

Flu is an infectious disease of birds and mammals caused by RNA viruses of the family Orthomyxoviridae, the influenza viruses. Flu or FLU may also refer to:

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Avian influenza

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Fowl cholera

Fowl cholera is also called avian cholera , avian pasteurellosis and avian hemorrhagic septicemia . It is the most common pasteurellosis of poultry . As the causative agent is Pasteurella multocida , it is considered to be a zoonosis . Adult birds and old chickens are more susceptible. In parental flocks, cocks are far more susceptible than hens. Besides chickens , the disease also concerns turkeys , ducks , geese , raptors , and canaries . Turkeys are particularly sensitive, with mortality ranging to 65%. The recognition of this pathological condition is of ever increasing importance for differential diagnosis with avian influenza .The disease was first recorded in the 18th century. In 1879, Pasteur received a bacterial sample from Jean Joseph Henri Toussaint DVM, Professor, Toulouse Veterinary College who had been working with Fowl Cholera. Louis Pasteur then isolated and grew it in pure culture. Originally a disease of fowl in Europe, it was first recorded in North America in 1943–44. Since then outbreaks have been recorded almost annually in wild birds. Today, this disease is most prevalent in wild waterfowl of North America. In December 1880, Pasteur announced to the French Academy of Sciences that he was working on a vaccine against fowl cholera. In fact, Pasteur's vaccine had irregular effects and was a failure. In 2011 an outbreak of avian cholera killed thousands of eider ducks in Arctic regions of Canada . Scientists are studying the outbreak and its potential to spread to Greenland . In March 2015, another outbreak of avian cholera killed roughly 2,000 snow geese in northern Idaho while flying their spring migration to Canada. Outbreaks occur in cold and wet weather (in late summer, fall and winter). The outbreaks are often traced back to the presence of rodents in the breeding houses. These are thought to spread the disease from carcasses of dead birds (possibly from neighboring backyards), improperly disposed of. Once the disease is introduced to a flock, it will stay until culling . Chronic carriers can always lead to re-emerging of the disease in susceptible birds... In wild birds, this disease is most commonly associated with wetlands . Blanchong et al. determined that wetlands act as short term reservoirs, recording large amounts of the bacterium in the soil and water through the duration of the outbreak. Wetlands, however, are not long term reservoirs. The disease presents in two very different forms: acute and chronic. Birds with chronic avian cholera, more common in domestic fowl, exhibit prolonged illness with more localized infections. Chronic infection has been demonstrated in snow geese, and these individuals are believed to be long term migrating reservoirs for the disease. Once the bacteria gets introduced into a population of susceptible birds, an outbreak of acute avian cholera follows. Infected birds will die 6–12 hours after contracting the bacterium, and very few ill birds have been described. Due to association and dense aggregations, waterfowl are most commonly affected by P. multocida , however scavengers and other water birds are often affected in large multi-species outbreaks. In acute cases, a green diarrhea can be an early symptom. The most typical symptom, in chronic cases, is the swelling of the wattles . It is more frequent in resistant local breeds. Rather than a general infection, localized infections are more characteristic. These often occur in the respiratory tract including the sinuses and pneumatics bones, hock joints, sternal bursa, foot pads, peritoneal cavity and oviducts. In acute cases, the most typical post-mortem lesion is the petechiae observed in the epicardial fatty tissue. Necrotic foci on liver are usually found and general hyperemia is common. Due to the speed of infection and mortality, birds are in good body condition and do not exhibit the signs of prolonged illness.The most efficient treatment in breeding flocks or laying hens is individual intramuscular injections of a long-acting tetracycline , with the same antibiotic in drinking water, simultaneously. The mortality and clinical signs will stop within one week, but the bacteria might remain present in the flock.

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Avian influenza

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Hemagglutination assay

The hemagglutination assay or haemagglutination assay ( HA ) and the hemagglutination inhibition assay ( HI or HAI ) were developed in 1941–42 by American virologist George Hirst as methods for quantifying the relative concentration of viruses , bacteria , or antibodies. HA and HAI apply the process of hemagglutination , in which sialic acid receptors on the surface of red blood cells (RBCs) bind to the hemagglutinin glycoprotein found on the surface of influenza virus (and several other viruses) and create a network, or lattice structure, of interconnected RBCs and virus particles. The agglutinated lattice maintains the RBCs in a suspended distribution, typically viewed as a diffuse reddish solution. The formation of the lattice depends on the concentrations of the virus and RBCs, and when the relative virus concentration is too low, the RBCs are not constrained by the lattice and settle to the bottom of the well. Hemagglutination is observed in the presence of staphylococci, vibrios, and other bacterial species, similar to the mechanism viruses use to cause agglutination of erythrocytes. The RBCs used in HA and HI assays are typically from chickens, turkeys, horses, guinea pigs, or humans depending on the selectivity of the targeted virus or bacterium and the associated surface receptors on the RBC.A general procedure for HA is as follows, a serial dilution of virus is prepared across the rows in a U or V- bottom shaped 96-well microtiter plate. The most concentrated sample in the first well is often diluted to be 1/5x of the stock, and subsequent wells are typically two-fold dilutions (1/10, 1/20, 1/40, etc.).The final well serves as a negative control with no virus. Each row of the plate typically has a different virus and the same pattern of dilutions. After serial dilutions, a standardized concentration of RBCs is added to each well and mixed gently. The plate is incubated for 30 minutes at room temperature. Following the incubation period, the assay can be analyzed to distinguish between agglutinated and non-agglutinated wells. The images across a row will typically progress from agglutinated wells with high virus concentration and a diffuse reddish appearance to a series of wells with low virus concentrations containing a dark red pellet, or button, in the center of the well. The low concentration wells appear nearly identical to the no-virus negative control well. The button appearance occurs because the RBCs are not held in the agglutinated lattice structure and settle into the low point of the U or V-bottom well. The transition from agglutinated to non-agglutinated wells occurs distinctively, within 1 to 2 wells. The relative concentration, or titer, of the virus sample is based on the well with the last agglutinated appearance, immediately before a pellet is observed. Relative to the initial viral stock concentration, the virus concentration in this well will be some dilution of the stock, for example, 1/40-fold. The titer value of that sample is the inverse of the dilution, i.e., 40. In some cases, the virus is initially so dilute that agglutinated wells are never observed. In that case, the titer of these samples is commonly assigned as 5, indicating the highest possible concentration, but the accuracy of that value is clearly low. Alternatively, if the relative concentration of the virus is extremely high and the wells never transition to a button appearance. The titer value is then commonly assigned to be the highest dilution, such as 5120. HI is closely related to the HA assay, but includes anti-viral antibodies as "inhibitors" to interfere with the virus-RBC interaction. The goal is to characterize the concentration of antibodies in the antiserum or other samples containing antibodies. The HI assay is generally performed by creating a dilution series of antiserum across the rows of a 96-well microtiter plate. Each row would usually be a different sample. A standardized amount of virus or bacteria is added to each well, and the mixture is allowed to incubate at room temperature for 30 minutes. The last well in each row would be a negative control with no virus added. During the incubation, antibodies bind to the viral particles, and if the concentration and binding affinity of the antibodies are high enough, the viral particles are effectively blocked from causing hemagglutination. Next, a standardized amount of RBCs is added to each well and allowed to incubate at room temperature for an additional 30 minutes. The resulting HI plate images usually progress from non-agglutinated, "button" wells with high antibody concentration to agglutinated, red diffuse wells with low antibody concentration. The HI titer value is the inverse of the last dilution of serum that completely inhibited hemagglutination. The preceding descriptions of the HA and HI processes are generalized, and specific details can vary depending on the operator and laboratory. For example, serial dilutions across the rows is described, but some laboratories use an alternate orientation and perform dilutions down the columns instead. Similarly, the starting dilution, serial dilution factor, incubation times, and choice of U or V-bottom plate can depend on the specific laboratory.HA and HI have the advantages that the assays are simple, use relatively inexpensive and available instruments and supplies, and provide results within a few hours. The assays are also well established in many laboratories around the world, allowing some measure of credibility, comparison, and standardization. Optimal and reliable results require controlling several variables, such as incubation times, red blood cell concentration, and type of red blood cell. Non-specific factors in the sample can lead to interference and incorrect titer values. For example, molecules in the sample other than virus-specific antibodies can inhibit agglutination between virus and RBCs, as well as potentially blocking antibody from binding to virus. Receptor-destroying enzymes (RDE) are commonly used to treat samples prior to analysis to prevent non-specific inhibition. Analysis of the HA or HI results relies on a qualified individual to read the plate and determine the titer values. The manual interpretation method introduces more opportunities for discrepancies in the assay because results can be subjective and the agreement between human readers is inconsistent. Also, there is no digital record of the plate or titer determinations so the initial interpretation is tedious and commonly done in replicates. The range of potential variables and differences between expert readers can make comparing inter-laboratory results difficult.

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Avian influenza

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Marek's disease

Gallid herpesvirus 2 Marek's disease is a highly contagious viral neoplastic disease in chickens . It is named after József Marek , a Hungarian veterinarian who described it in 1907. Marek's disease is caused by an alphaherpesvirus known as "Marek's disease virus" (MDV) or Gallid alphaherpesvirus 2 (GaHV-2). The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes . Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related herpesvirus found in turkeys (HVT), causes no apparent disease in the birds, and continues to be used as a vaccine strain for prevention of Marek's disease. Birds infected with GaHV-2 can be carriers and shedders of the virus for life. Newborn chicks are protected by maternal antibodies for a few weeks. After infection, microscopic lesions are present after one to two weeks, and gross lesions are present after three to four weeks. The virus is spread in dander from feather follicles and transmitted by inhalation. Six syndromes are known to occur after infection with Marek's disease. These syndromes may overlap.Diagnosis of lymphoid tumors in poultry is complicated due to multiple etiological agents capable of causing very similar tumors. It is not uncommon that more than one avian tumor virus can be present in a chicken, thus one must consider both the diagnosis of the disease/tumors (pathological diagnosis) and of the virus (etiological diagnosis). A step-wise process has been proposed for diagnosis of Marek's disease, which includes: History, epidemiology, clinical observations and gross necropsy; Characteristics of the tumor cell, and; Virological characteristics The demonstration of peripheral nerve enlargement along with suggestive clinical signs in a bird that is around three to four months old (with or without visceral tumors) is highly suggestive of Marek's disease. Histological examination of nerves reveals infiltration of pleomorphic neoplastic and inflammatory lymphocytes. Peripheral neuropathy should also be considered as a principal rule-out in young chickens with paralysis and nerve enlargement without visceral tumors, especially in nerves with interneuronal edema and infiltration of plasma cells. The presence of nodules on the internal organs may also suggest Marek's disease, but further testing is required for confirmation. This is done through histological demonstration of lymphomatous infiltration into the affected tissue. A range of leukocytes can be involved, including lymphocytic cell lines such as large lymphocyte, lymphoblast, primitive reticular cells, and occasional plasma cells, as well as macrophage and plasma cells. The T cells are involved in the malignancy, showing neoplastic changes with evidence of mitosis. The lymphomatous infiltrates need to be differentiated from other conditions that affect poultry including lymphoid leukosis and reticuloendotheliosis, as well as an inflammatory event associated with hyperplastic changes of the affected tissue. Key clinical signs as well as gross and microscopic features that are most useful for differentiating Marek's disease from lymphoid leukosis and reticuloendotheliosis include: Age: Marek's disease can affect birds at any age, including 5% in unvaccinated flocks; Potential nerve enlargement; Interfollicular tumors in the bursa of Fabricius; CNS involvement; Lymphoid proliferation in skin and feather follicles; Pleomorphic lymphoid cells in nerves and tumors; and T-cell lymphomas. In addition to gross pathology and histology, other advanced procedures used for a definitive diagnosis of Marek's disease include immunohistochemistry to identify cell type and virus-specific antigens, standard and quantitative PCR for identification of the virus, virus isolation to confirm infections, and serology to confirm/exclude infections. The World Organisation for Animal Health (OIE) reference laboratory for Marek's disease is Avian Viral Oncogenesis group (led by Professor Venugopal Nair OBE) at The Pirbright Institute, UK. PCR blood testing can also detect Marek's disease, and proper testing can differentiate between a vaccinated bird with antibodies and a true positive for Marek's disease. Marek's disease is not treatable, however, supportive care can help. It is recommended that all flocks positive for Marek's disease remain closed, with no bird being introduced or leaving the flock. Strict biosecurity and proper cleaning is essential, using products like Activated Oxine or Virkon S and reducing dander buildup in the environment. Proper diet, regular deworming and vitamin supplements can also help keep infected flocks healthier. Reducing stress is also a key component, as stress will often bring about illness in birds infected with Marek's disease.Vaccination is the only known method to prevent the development of tumors when chickens are infected with the virus. However, administration of the vaccine does not prevent an infected bird from shedding the virus, though it does reduce the amount of virus shed in the dander, hence reducing horizontal spread of the disease. Marek's disease does not spread vertically . Before the development of the vaccine for Marek's disease, Marek's disease caused substantial revenue loss in the poultry industries of the United States and the United Kingdom. The vaccine can be administered to one-day-old chicks through subcutaneous inoculation or by in ovo vaccination when the eggs are transferred from the incubator to the hatcher. In ovo vaccination is the preferred method, as it does not require handling of the chicks and can be done rapidly by automated methods. Immunity develops within two weeks. Because vaccination does not prevent infection with the virus, Marek's is still transmissible from vaccinated flocks to other birds, including the wild bird population. The first Marek's disease vaccine was introduced in 1970. The disease would cause mild paralysis, with the only identifiable lesions being in neural tissue. Mortality of chickens infected with Marek's disease was quite low. Current strains of Marek virus, decades after the first vaccine was introduced, cause lymphoma formation throughout the chicken's body and mortality rates have reached 100% in unvaccinated chickens. The Marek's disease vaccine is a "leaky vaccine", which means that only the symptoms of the disease are prevented. Infection of the host and the transmission of the virus are not inhibited by the vaccine. This contrasts with most other vaccines, where infection of the host is prevented. Under normal conditions, highly virulent strains of the virus are not selected for by evolution. This is because such a severe strain would kill the host before the virus would have an opportunity to transmit to other potential hosts and replicate. Thus, less virulent strains are selected. These strains are virulent enough to induce symptoms but not enough to kill the host, allowing further transmission. However, the leaky vaccine changes this evolutionary pressure and permits the evolution of highly virulent strains. The vaccine's inability to prevent infection and transmission allows the spread of highly virulent strains among vaccinated chickens. The fitness of the more virulent strains is increased by the vaccine. The evolution of Marek's disease due to vaccination has had a profound effect on the poultry industry. All chickens across the globe are now vaccinated against Marek's disease (birds hatched in private flocks for laying or exhibition are rarely vaccinated). Highly virulent strains have been selected to the point that any chicken that is unvaccinated will die if infected. Other leaky vaccines are commonly used in agriculture. One vaccine in particular is the vaccine for avian influenza. Leaky vaccine use for avian influenza can select for virulent strains.

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Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Maria_Van_Kerkhove/html

Maria Van Kerkhove

Maria DeJoseph Van Kerkhove (born February 20, 1977) is an American infectious disease epidemiologist . With a background in high-threat pathogens , Van Kerkhove specializes in emerging and re-emerging infectious diseases and is based in the Health Emergencies Program at the World Health Organization (WHO). She is the technical lead of COVID-19 response and the head of emerging diseases and zoonosis unit at WHO. Van Kerkhove was born Maria Rosanne DeJoseph in New Hartford, New York . In 1999, she received a B.S. in biological sciences from Cornell University . In 2000, she received an M.S. in epidemiology from Stanford University School of Medicine . In 2009, she earned a Ph.D. in infectious disease epidemiology from the London School of Hygiene & Tropical Medicine , where she wrote her thesis on the avian flu in Cambodia . Van Kerkhove began her research career while an undergraduate student at Cornell University. She worked as a research assistant with Eloy Rodriguez studying the medical plants of the Amazon . As a masters student, she continued as a research assistant at Stanford University Medical School. From 2000 to 2005, Van Kerkhove was a senior epidemiologist at Exponent 's health sciences practice in New York City. After this, she worked as an epidemiologist at the Institut Pasteur de Cambodia from 2006 to 2008, while conducting field studies on H5N1 for her Ph.D. Van Kerkhove was a senior research fellow in the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London from 2009 to 2015. She specialized in Ebola, Marburg, influenza , meningitis , MERS-CoV , and yellow fever . In April 2009, she began working as a technical consultant to the World Health Organization (WHO) in its Global Capacities, Alert and Response Cluster. In 2013, she was a technical consultant for WHO as a member of the MERS-CoV task force. From 2015 to 2017, Van Kerkhove was the head of the Outbreak Investigation Task Force at the Institut Pasteur's Center for Global Health, conducting field research into surrounding zoonoses , respiratory viruses and emerging/re-emerging viruses such as Zika, MERS-CoV, Ebola and Marburg . She specialized in field research to gather data on the highly pathogenic avian influenza H5N1 (HPAI/H5N1), with a focus on transmission risk from poultry to humans. Van Kerkhove has been an honorary lecturer at Imperial College London since 2015. She has been Scientist, Technical Lead MERS-CoV at WHO in Geneva, Switzerland , since March 2017. She is currently the head of the Emerging Diseases and Zoonoses Unit in the WHO Health Emergencies Programme. She also serves as the COVID-19 technical and health operations lead. As part of her work with WHO, Van Kerkhove appears in regular press conferences by WHO regarding the COVID-19 pandemic . Van Kerkhove has provided answers to common questions about the pandemic . Van Kerkhove spent two weeks in China in February 2020 to better understand the COVID-19 pandemic and to understand how China was trying to control the virus. Van Kerkhove lives in Geneva, Switzerland, with her husband Neil and two sons.

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Avian influenza

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Zoonosis

A zoonosis ( / z oʊ ˈ ɒ n ə s ɪ s , ˌ z oʊ ə ˈ n oʊ s ɪ s / ; plural zoonoses ) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium , virus , parasite , or prion ) that can jump from a non-human (usually a vertebrate ) to a human and vice versa. Major modern diseases such as Ebola and salmonellosis are zoonoses. HIV was a zoonotic disease transmitted to humans in the early part of the 20th century, though it has now evolved into a separate human-only disease. Human infection with animal influenza viruses is rare, as they do not transmit easily to or among humans. However, avian and swine influenza viruses in particular possess high zoonotic potential, and these occasionally recombine with human strains of the flu and can cause pandemics such as the 2009 swine flu . Taenia solium infection is one of the neglected tropical diseases with public health and veterinary concern in endemic regions. Zoonoses can be caused by a range of disease pathogens such as emergent viruses , bacteria, fungi and parasites; of 1,415 pathogens known to infect humans, 61% were zoonotic. Most human diseases originated in non-humans; however, only diseases that routinely involve non-human to human transmission, such as rabies , are considered direct zoonoses. Zoonoses have different modes of transmission. In direct zoonosis the disease is directly transmitted from non-humans to humans through media such as air (influenza) or bites and saliva (rabies). In contrast, transmission can also occur via an intermediate species (referred to as a vector ), which carry the disease pathogen without getting sick. When humans infect non-humans, it is called reverse zoonosis or anthroponosis. The term is from Greek : ζῷον zoon "animal" and νόσος nosos "sickness". Host genetics plays an important role in determining which non-human viruses will be able to make copies of themselves in the human body. Dangerous non-human viruses are those that require few mutations to begin replicating themselves in human cells. These viruses are dangerous since the required combinations of mutations might randomly arise in the natural reservoir . The emergence of zoonotic diseases originated with the domestication of animals. Zoonotic transmission can occur in any context in which there is contact with or consumption of animals, animal products, or animal derivatives. This can occur in a companionistic (pets), economic (farming, trade, butchering, etc.), predatory (hunting, butchering, or consuming wild game), or research context. Recently, there has been a rise in frequency of appearance of new zoonotic diseases. "Approximately 1.67 million undescribed viruses are thought to exist in mammals and birds, up to half of which are estimated to have the potential to spill over into humans", says a study led by researchers at the University of California, Davis . According to a report from the United Nations Environment Programme and International Livestock Research Institute a large part of the causes are environmental like climate change , unsustainable agriculture, exploitation of wildlife, and land use change . Others are linked to changes in human society such as an increase in mobility. The organizations propose a set of measures to stop the rise. The most significant zoonotic pathogens causing foodborne diseases are Escherichia coli O157:H7 , Campylobacter , Caliciviridae , and Salmonella . In 2006 a conference held in Berlin focused on the issue of zoonotic pathogen effects on food safety , urging government intervention and public vigilance against the risks of catching food-borne diseases from farm-to-table dining. Many food-borne outbreaks can be linked to zoonotic pathogens. Many different types of food that have an animal origin can become contaminated. Some common food items linked to zoonotic contaminations include eggs, seafood, meat, dairy, and even some vegetables. Outbreaks involving contaminated food should be handled in preparedness plans to prevent widespread outbreaks and to efficiently and effectively contain outbreaks. Contact with farm animals can lead to disease in farmers or others that come into contact with infected farm animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses , tanneries , and wool mills . Close contact with sheep who have recently given birth can lead to infection with the bacterium Chlamydia psittaci , causing chlamydiosis (and enzootic abortion in pregnant women), as well as increase the risk of Q fever , toxoplasmosis , and listeriosis , in the pregnant or otherwise immunocompromised . Echinococcosis is caused by a tapeworm, which can spread from infected sheep by food or water contaminated by feces or wool. Avian influenza is common in chickens, and, while it is rare in humans, the main public health worry is that a strain of avian influenza will recombine with a human influenza virus and cause a pandemic like the 1918 Spanish flu . [ citation needed ] In 2017, free-range chickens in the UK were temporarily ordered to remain inside due to the threat of avian influenza. Cattle are an important reservoir of cryptosporidiosis , which mainly affects the immunocompromised. Reports have shown mink can also become infected. In Western countries, hepatitis E burden is largely dependent on exposure to animal products, and pork is a significant source of infection, in this respect. Veterinarians are exposed to unique occupational hazards when it comes to zoonotic disease. In the US, studies have highlighted an increased risk of injuries and lack of veterinary awareness of these hazards. Research has proved the importance for continued clinical veterinarian education on occupational risks associated with musculoskeletal injuries, animal bites, needle-sticks, and cuts. A July 2020 report by the United Nations Environment Programme stated that the increase in zoonotic pandemics is directly attributable to anthropogenic destruction of nature and the increased global demand for meat and that the industrial farming of pigs and chickens in particular will be a primary risk factor for the spillover of zoonotic diseases in the future. Habitat loss of viral reservoir species has been identified as a significant source in at least one spillover event . The wildlife trade may increase spillover risk because it directly increases the number of interactions across animal species, sometimes in small spaces. The origin of the ongoing COVID-19 pandemic is traced to the wet markets in China . Zoonotic disease emergence is demonstrably linked to the consumption of wildlife meat, exacerbated by human encroachment into natural habitats and amplified by the unsanitary conditions of wildlife markets. These markets, where diverse species converge, facilitate the mixing and transmission of pathogens, including those responsible for outbreaks of HIV-1, Ebola, and mpox , and potentially even the COVID-19 pandemic. Notably, small mammals often harbor a vast array of zoonotic bacteria and viruses, yet endemic bacterial transmission among wildlife remains largely unexplored. Therefore, accurately determining the pathogenic landscape of traded wildlife is crucial for guiding effective measures to combat zoonotic diseases and documenting the societal and environmental costs associated with this practice. Pets can transmit a number of diseases. Dogs and cats are routinely vaccinated against rabies . Pets can also transmit ringworm and Giardia , which are endemic in both animal and human populations. Toxoplasmosis is a common infection of cats; in humans it is a mild disease although it can be dangerous to pregnant women. Dirofilariasis is caused by Dirofilaria immitis through mosquitoes infected by mammals like dogs and cats. Cat-scratch disease is caused by Bartonella henselae and Bartonella quintana , which are transmitted by fleas that are endemic to cats. Toxocariasis is the infection of humans by any of species of roundworm , including species specific to dogs ( Toxocara canis ) or cats ( Toxocara cati ). Cryptosporidiosis can be spread to humans from pet lizards, such as the leopard gecko . Encephalitozoon cuniculi is a microsporidial parasite carried by many mammals, including rabbits, and is an important opportunistic pathogen in people immunocompromised by HIV/AIDS , organ transplantation , or CD4+ T-lymphocyte deficiency. Pets may also serve as a reservoir of viral disease and contribute to the chronic presence of certain viral diseases in the human population. For instance, approximately 20% of domestic dogs, cats, and horses carry anti-hepatitis E virus antibodies and thus these animals probably contribute to human hepatitis E burden as well. For non-vulnerable populations (e.g., people who are not immunocompromised) the associated disease burden is, however, small. [ citation needed ] Furthermore, the trade of non domestic animals such as wild animals as pets can also increase the risk of zoonosis spread. Outbreaks of zoonoses have been traced to human interaction with, and exposure to, other animals at fairs , live animal markets , petting zoos , and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians , include educational responsibilities of venue operators, limiting public animal contact, and animal care and management. Hunting involves humans tracking, chasing, and capturing wild animals, primarily for food or materials like fur. However, other reasons like pest control or managing wildlife populations can also exist. Transmission of zoonotic diseases, those leaping from animals to humans, can occur through various routes: direct physical contact, airborne droplets or particles, bites or vector transport by insects, oral ingestion, or even contact with contaminated environments. Wildlife activities like hunting and trade bring humans closer to dangerous zoonotic pathogens, threatening global health. According to the Center for Diseases Control and Prevention (CDC) hunting and consuming wild animal meat ("bushmeat") in regions like Africa can expose people to infectious diseases due to the types of animals involved, like bats and primates. Unfortunately, common preservation methods like smoking or drying aren't enough to eliminate these risks. Although bushmeat provides protein and income for many, the practice is intricately linked to numerous emerging infectious diseases like Ebola, HIV, and SARS , raising critical public health concerns. A review published in 2022 found evidence that zoonotic spillover linked to wildmeat consumption has been reported across all continents. Kate Jones , Chair of Ecology and Biodiversity at University College London , says zoonotic diseases are increasingly linked to environmental change and human behavior. The disruption of pristine forests driven by logging, mining, road building through remote places, rapid urbanization, and population growth is bringing people into closer contact with animal species they may never have been near before. The resulting transmission of disease from wildlife to humans, she says, is now "a hidden cost of human economic development". In a guest article, published by IPBES , President of the EcoHealth Alliance and zoologist Peter Daszak , along with three co-chairs of the 2019 Global Assessment Report on Biodiversity and Ecosystem Services , Josef Settele, Sandra Díaz , and Eduardo Brondizio, wrote that "rampant deforestation, uncontrolled expansion of agriculture, intensive farming , mining and infrastructure development, as well as the exploitation of wild species have created a 'perfect storm' for the spillover of diseases from wildlife to people." Joshua Moon, Clare Wenham, and Sophie Harman said that there is evidence that decreased biodiversity has an effect on the diversity of hosts and frequency of human-animal interactions with potential for pathogenic spillover. An April 2020 study, published in the Proceedings of the Royal Society ' s Part B journal, found that increased virus spillover events from animals to humans can be linked to biodiversity loss and environmental degradation , as humans further encroach on wildlands to engage in agriculture, hunting, and resource extraction they become exposed to pathogens which normally would remain in these areas. Such spillover events have been tripling every decade since 1980. An August 2020 study, published in Nature , concludes that the anthropogenic destruction of ecosystems for the purpose of expanding agriculture and human settlements reduces biodiversity and allows for smaller animals such as bats and rats, which are more adaptable to human pressures and also carry the most zoonotic diseases, to proliferate. This in turn can result in more pandemics. In October 2020, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services published its report on the 'era of pandemics' by 22 experts in a variety of fields and concluded that anthropogenic destruction of biodiversity is paving the way to the pandemic era and could result in as many as 850,000 viruses being transmitted from animals – in particular birds and mammals – to humans. The increased pressure on ecosystems is being driven by the "exponential rise" in consumption and trade of commodities such as meat, palm oil , and metals, largely facilitated by developed nations, and by a growing human population . According to Peter Daszak, the chair of the group who produced the report, "there is no great mystery about the cause of the Covid-19 pandemic, or of any modern pandemic. The same human activities that drive climate change and biodiversity loss also drive pandemic risk through their impacts on our environment." According to a report from the United Nations Environment Programme and International Livestock Research Institute , entitled "Preventing the next pandemic – Zoonotic diseases and how to break the chain of transmission", climate change is one of the 7 human-related causes of the increase in the number of zoonotic diseases. The University of Sydney issued a study, in March 2021, that examines factors increasing the likelihood of epidemics and pandemics like the COVID-19 pandemic. The researchers found that "pressure on ecosystems, climate change and economic development are key factors" in doing so. More zoonotic diseases were found in high-income countries . A 2022 study dedicated to the link between climate change and zoonosis found a strong link between climate change and the epidemic emergence in the last 15 years, as it caused a massive migration of species to new areas, and consequently contact between species which do not normally come in contact with one another. Even in a scenario with weak climatic changes, there will be 15,000 spillover of viruses to new hosts in the next decades. The areas with the most possibilities for spillover are the mountainous tropical regions of Africa and southeast Asia. Southeast Asia is especially vulnerable as it has a large number of bat species that generally do not mix, but could easily if climate change forced them to begin migrating. A 2021 study found possible links between climate change and transmission of COVID-19 through bats. The authors suggest that climate-driven changes in the distribution and robustness of bat species harboring coronaviruses may have occurred in eastern Asian hotspots (southern China, Myanmar, and Laos), constituting a driver behind the evolution and spread of the virus. The most significant zoonotic pathogens causing foodborne diseases are Escherichia coli O157:H7 , Campylobacter , Caliciviridae , and Salmonella . In 2006 a conference held in Berlin focused on the issue of zoonotic pathogen effects on food safety , urging government intervention and public vigilance against the risks of catching food-borne diseases from farm-to-table dining. Many food-borne outbreaks can be linked to zoonotic pathogens. Many different types of food that have an animal origin can become contaminated. Some common food items linked to zoonotic contaminations include eggs, seafood, meat, dairy, and even some vegetables. Outbreaks involving contaminated food should be handled in preparedness plans to prevent widespread outbreaks and to efficiently and effectively contain outbreaks. Contact with farm animals can lead to disease in farmers or others that come into contact with infected farm animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses , tanneries , and wool mills . Close contact with sheep who have recently given birth can lead to infection with the bacterium Chlamydia psittaci , causing chlamydiosis (and enzootic abortion in pregnant women), as well as increase the risk of Q fever , toxoplasmosis , and listeriosis , in the pregnant or otherwise immunocompromised . Echinococcosis is caused by a tapeworm, which can spread from infected sheep by food or water contaminated by feces or wool. Avian influenza is common in chickens, and, while it is rare in humans, the main public health worry is that a strain of avian influenza will recombine with a human influenza virus and cause a pandemic like the 1918 Spanish flu . [ citation needed ] In 2017, free-range chickens in the UK were temporarily ordered to remain inside due to the threat of avian influenza. Cattle are an important reservoir of cryptosporidiosis , which mainly affects the immunocompromised. Reports have shown mink can also become infected. In Western countries, hepatitis E burden is largely dependent on exposure to animal products, and pork is a significant source of infection, in this respect. Veterinarians are exposed to unique occupational hazards when it comes to zoonotic disease. In the US, studies have highlighted an increased risk of injuries and lack of veterinary awareness of these hazards. Research has proved the importance for continued clinical veterinarian education on occupational risks associated with musculoskeletal injuries, animal bites, needle-sticks, and cuts. A July 2020 report by the United Nations Environment Programme stated that the increase in zoonotic pandemics is directly attributable to anthropogenic destruction of nature and the increased global demand for meat and that the industrial farming of pigs and chickens in particular will be a primary risk factor for the spillover of zoonotic diseases in the future. Habitat loss of viral reservoir species has been identified as a significant source in at least one spillover event . The wildlife trade may increase spillover risk because it directly increases the number of interactions across animal species, sometimes in small spaces. The origin of the ongoing COVID-19 pandemic is traced to the wet markets in China . Zoonotic disease emergence is demonstrably linked to the consumption of wildlife meat, exacerbated by human encroachment into natural habitats and amplified by the unsanitary conditions of wildlife markets. These markets, where diverse species converge, facilitate the mixing and transmission of pathogens, including those responsible for outbreaks of HIV-1, Ebola, and mpox , and potentially even the COVID-19 pandemic. Notably, small mammals often harbor a vast array of zoonotic bacteria and viruses, yet endemic bacterial transmission among wildlife remains largely unexplored. Therefore, accurately determining the pathogenic landscape of traded wildlife is crucial for guiding effective measures to combat zoonotic diseases and documenting the societal and environmental costs associated with this practice.Pets can transmit a number of diseases. Dogs and cats are routinely vaccinated against rabies . Pets can also transmit ringworm and Giardia , which are endemic in both animal and human populations. Toxoplasmosis is a common infection of cats; in humans it is a mild disease although it can be dangerous to pregnant women. Dirofilariasis is caused by Dirofilaria immitis through mosquitoes infected by mammals like dogs and cats. Cat-scratch disease is caused by Bartonella henselae and Bartonella quintana , which are transmitted by fleas that are endemic to cats. Toxocariasis is the infection of humans by any of species of roundworm , including species specific to dogs ( Toxocara canis ) or cats ( Toxocara cati ). Cryptosporidiosis can be spread to humans from pet lizards, such as the leopard gecko . Encephalitozoon cuniculi is a microsporidial parasite carried by many mammals, including rabbits, and is an important opportunistic pathogen in people immunocompromised by HIV/AIDS , organ transplantation , or CD4+ T-lymphocyte deficiency. Pets may also serve as a reservoir of viral disease and contribute to the chronic presence of certain viral diseases in the human population. For instance, approximately 20% of domestic dogs, cats, and horses carry anti-hepatitis E virus antibodies and thus these animals probably contribute to human hepatitis E burden as well. For non-vulnerable populations (e.g., people who are not immunocompromised) the associated disease burden is, however, small. [ citation needed ] Furthermore, the trade of non domestic animals such as wild animals as pets can also increase the risk of zoonosis spread. Outbreaks of zoonoses have been traced to human interaction with, and exposure to, other animals at fairs , live animal markets , petting zoos , and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians , include educational responsibilities of venue operators, limiting public animal contact, and animal care and management.Hunting involves humans tracking, chasing, and capturing wild animals, primarily for food or materials like fur. However, other reasons like pest control or managing wildlife populations can also exist. Transmission of zoonotic diseases, those leaping from animals to humans, can occur through various routes: direct physical contact, airborne droplets or particles, bites or vector transport by insects, oral ingestion, or even contact with contaminated environments. Wildlife activities like hunting and trade bring humans closer to dangerous zoonotic pathogens, threatening global health. According to the Center for Diseases Control and Prevention (CDC) hunting and consuming wild animal meat ("bushmeat") in regions like Africa can expose people to infectious diseases due to the types of animals involved, like bats and primates. Unfortunately, common preservation methods like smoking or drying aren't enough to eliminate these risks. Although bushmeat provides protein and income for many, the practice is intricately linked to numerous emerging infectious diseases like Ebola, HIV, and SARS , raising critical public health concerns. A review published in 2022 found evidence that zoonotic spillover linked to wildmeat consumption has been reported across all continents. Kate Jones , Chair of Ecology and Biodiversity at University College London , says zoonotic diseases are increasingly linked to environmental change and human behavior. The disruption of pristine forests driven by logging, mining, road building through remote places, rapid urbanization, and population growth is bringing people into closer contact with animal species they may never have been near before. The resulting transmission of disease from wildlife to humans, she says, is now "a hidden cost of human economic development". In a guest article, published by IPBES , President of the EcoHealth Alliance and zoologist Peter Daszak , along with three co-chairs of the 2019 Global Assessment Report on Biodiversity and Ecosystem Services , Josef Settele, Sandra Díaz , and Eduardo Brondizio, wrote that "rampant deforestation, uncontrolled expansion of agriculture, intensive farming , mining and infrastructure development, as well as the exploitation of wild species have created a 'perfect storm' for the spillover of diseases from wildlife to people." Joshua Moon, Clare Wenham, and Sophie Harman said that there is evidence that decreased biodiversity has an effect on the diversity of hosts and frequency of human-animal interactions with potential for pathogenic spillover. An April 2020 study, published in the Proceedings of the Royal Society ' s Part B journal, found that increased virus spillover events from animals to humans can be linked to biodiversity loss and environmental degradation , as humans further encroach on wildlands to engage in agriculture, hunting, and resource extraction they become exposed to pathogens which normally would remain in these areas. Such spillover events have been tripling every decade since 1980. An August 2020 study, published in Nature , concludes that the anthropogenic destruction of ecosystems for the purpose of expanding agriculture and human settlements reduces biodiversity and allows for smaller animals such as bats and rats, which are more adaptable to human pressures and also carry the most zoonotic diseases, to proliferate. This in turn can result in more pandemics. In October 2020, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services published its report on the 'era of pandemics' by 22 experts in a variety of fields and concluded that anthropogenic destruction of biodiversity is paving the way to the pandemic era and could result in as many as 850,000 viruses being transmitted from animals – in particular birds and mammals – to humans. The increased pressure on ecosystems is being driven by the "exponential rise" in consumption and trade of commodities such as meat, palm oil , and metals, largely facilitated by developed nations, and by a growing human population . According to Peter Daszak, the chair of the group who produced the report, "there is no great mystery about the cause of the Covid-19 pandemic, or of any modern pandemic. The same human activities that drive climate change and biodiversity loss also drive pandemic risk through their impacts on our environment." According to a report from the United Nations Environment Programme and International Livestock Research Institute , entitled "Preventing the next pandemic – Zoonotic diseases and how to break the chain of transmission", climate change is one of the 7 human-related causes of the increase in the number of zoonotic diseases. The University of Sydney issued a study, in March 2021, that examines factors increasing the likelihood of epidemics and pandemics like the COVID-19 pandemic. The researchers found that "pressure on ecosystems, climate change and economic development are key factors" in doing so. More zoonotic diseases were found in high-income countries . A 2022 study dedicated to the link between climate change and zoonosis found a strong link between climate change and the epidemic emergence in the last 15 years, as it caused a massive migration of species to new areas, and consequently contact between species which do not normally come in contact with one another. Even in a scenario with weak climatic changes, there will be 15,000 spillover of viruses to new hosts in the next decades. The areas with the most possibilities for spillover are the mountainous tropical regions of Africa and southeast Asia. Southeast Asia is especially vulnerable as it has a large number of bat species that generally do not mix, but could easily if climate change forced them to begin migrating. A 2021 study found possible links between climate change and transmission of COVID-19 through bats. The authors suggest that climate-driven changes in the distribution and robustness of bat species harboring coronaviruses may have occurred in eastern Asian hotspots (southern China, Myanmar, and Laos), constituting a driver behind the evolution and spread of the virus. During most of human prehistory groups of hunter-gatherers were probably very small. Such groups probably made contact with other such bands only rarely. Such isolation would have caused epidemic diseases to be restricted to any given local population, because propagation and expansion of epidemics depend on frequent contact with other individuals who have not yet developed an adequate immune response . To persist in such a population, a pathogen either had to be a chronic infection, staying present and potentially infectious in the infected host for long periods, or it had to have other additional species as reservoir where it can maintain itself until further susceptible hosts are contacted and infected. In fact, for many "human" diseases, the human is actually better viewed as an accidental or incidental victim and a dead-end host . Examples include rabies, anthrax, tularemia, and West Nile fever. Thus, much of human exposure to infectious disease has been zoonotic. Many diseases, even epidemic ones, have zoonotic origin and measles , smallpox , influenza , HIV, and diphtheria are particular examples. Various forms of the common cold and tuberculosis also are adaptations of strains originating in other species. [ citation needed ] Some experts have suggested that all human viral infections were originally zoonotic. Zoonoses are of interest because they are often previously unrecognized diseases or have increased virulence in populations lacking immunity. The West Nile virus first appeared in the United States in 1999 , in the New York City area. Bubonic plague is a zoonotic disease, as are salmonellosis , Rocky Mountain spotted fever , and Lyme disease . A major factor contributing to the appearance of new zoonotic pathogens in human populations is increased contact between humans and wildlife. This can be caused either by encroachment of human activity into wilderness areas or by movement of wild animals into areas of human activity. An example of this is the outbreak of Nipah virus in peninsular Malaysia, in 1999, when intensive pig farming began within the habitat of infected fruit bats. The unidentified infection of these pigs amplified the force of infection, transmitting the virus to farmers, and eventually causing 105 human deaths. Similarly, in recent times avian influenza and West Nile virus have spilled over into human populations probably due to interactions between the carrier host and domestic animals. [ citation needed ] Highly mobile animals, such as bats and birds, may present a greater risk of zoonotic transmission than other animals due to the ease with which they can move into areas of human habitation. Because they depend on the human host for part of their life-cycle, diseases such as African schistosomiasis , river blindness , and elephantiasis are not defined as zoonotic, even though they may depend on transmission by insects or other vectors . The first vaccine against smallpox by Edward Jenner in 1800 was by infection of a zoonotic bovine virus which caused a disease called cowpox . Jenner had noticed that milkmaids were resistant to smallpox. Milkmaids contracted a milder version of the disease from infected cows that conferred cross immunity to the human disease. Jenner abstracted an infectious preparation of 'cowpox' and subsequently used it to inoculate persons against smallpox. As a result of vaccination, smallpox has been eradicated globally, and mass inoculation against this disease ceased in 1981. There are a variety of vaccine types, including traditional inactivated pathogen vaccines, subunit vaccines , live attenuated vaccines . There are also new vaccine technologies such as viral vector vaccines and DNA/RNA vaccines , which include many of the COVID-19 vaccines .

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Avian influenza

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2008 H5N1 outbreak in West Bengal

The 2008 bird flu outbreak in West Bengal was an occurrence of avian influenza in West Bengal , India which began on January 16, 2008. The infection was caused by the H5N1 subtype of the Influenza A virus and impacted at least thirteen districts, including Birbhum , Nadia , Murshidabad , Burdwan , Hooghly , Cooch Behar , Malda , Bankura , Purulia , Howrah , West Midnapore , South 24 Parganas and South Dinajpur . A range of precautions has been instituted including a large cull of chickens , eggs , and poultry birds, the imposition of segregation zones, and a disinfection programme for the plant. [ citation needed ] The government put a blanket ban on the movement of poultry birds from West Bengal. [ citation needed ]The initial causes were not determined, but a high poultry density followed by a moist cold climate had led to the quick spread of the virus. With the highest population density in India, West Bengal had a high risk of the deadly virus spreading to humans. As per other accounts,{cn} bird flu had spread to half of the state due to delayed action, bad planning and mismanagement by Government of West Bengal. In many villages, people led by ruling party leaders resisted culling operations. . Agriculture Minister Sharad Pawar had slammed the Communist Party of India (Marxist) government for not reporting the bird flu epidemic early on. Shortage of staff for culling operation is one of the other reasons.{cn}At least eleven districts of West Bengal, including Birbhum , Nadia , Murshidabad , Burdwan , Hooghly , Cooch Behar , Malda , Bankura , Purulia , Howrah , West Midnapore , South 24 Parganas and South Dinajpur were affected by bird flu.

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Avian influenza

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Poultry

Poultry ( / ˈ p oʊ l t r i / ) are domesticated birds kept by humans for the purpose of harvesting animal products such as meat , eggs or feathers . The practice of raising poultry is known as poultry farming . These birds are most typically members of the superorder Galloanserae ( fowl ), especially the order Galliformes (which includes chickens , quails , and turkeys ). The term also includes waterfowls of the family Anatidae ( ducks and geese ) but does not include wild birds hunted for food known as game or quarry . Recent genomic studies involving the four extant junglefowl species reveals that the domestication of chicken, the most populous poultry species, occurred around 8,000 years ago in Southeast Asia . This was previously believed to have occurred around 5,400 years ago, also in Southeast Asia. The process may have originally occurred as a result of people hatching and rearing young birds from eggs collected from the wild, but later involved keeping the birds permanently in captivity . Domesticated chickens may have been used for cockfighting at first and quail kept for their songs, but people soon realised the advantages of having a captive-bred source of food. Selective breeding for fast growth, egg-laying ability, conformation, plumage and docility took place over the centuries, and modern breeds often look very different from their wild ancestors. Although some birds are still kept in small flocks in extensive systems, most birds available in the market today are reared in intensive commercial enterprises. Together with pork , poultry is one of the two most widely-eaten types of meat globally, with over 70% of the meat supply in 2012 between them; poultry provides nutritionally beneficial food containing high-quality protein accompanied by a low proportion of fat. All poultry meat should be properly handled and sufficiently cooked in order to reduce the risk of food poisoning . Semi-vegetarians who consume poultry as the only source of meat are said to adhere to pollotarianism .The word "poultry" comes from Middle English pultry or pultrie , itself derived from Old French / Norman word pouletrie . The term for an immature poultry, pullet , like its doublet poult , comes from Middle English pulet and Old French polet , both from the Latin word pullus , meaning a young fowl or young animal. The word "fowl" is of Germanic origin (cf. Old English Fugol , German Vogel , Danish Fugl ). "Poultry" is a term used for any kind of domesticated bird, captive-raised for its utility, and traditionally the word has been used to refer to wildfowl ( Galliformes ) and waterfowl ( Anseriformes ) but not to cagebirds such as songbirds and parrots . "Poultry" can be defined as domestic fowls, including chickens, turkeys, geese and ducks, raised for the production of meat or eggs and the word is also used for the flesh of these birds used as food. The Encyclopædia Britannica lists the same bird groups but also includes guinea fowl and squabs (young pigeons). In R. D. Crawford's Poultry breeding and genetics , squabs are omitted but Japanese quail and common pheasant are added to the list, the latter frequently being bred in captivity and released into the wild. In his 1848 classic book on poultry, Ornamental and Domestic Poultry: Their History, and Management , Edmund Dixon included chapters on the peafowl , guinea fowl , mute swan , turkey , various types of geese , the muscovy duck, other ducks and all types of chickens including bantams. In colloquial speech, the term "fowl" is often used near-synonymously with "domesticated chicken" ( Gallus gallus ), or with "poultry" or even just "bird", and many languages do not distinguish between "poultry" and "fowl". Both words are also used for the flesh of these birds. Poultry can be distinguished from "game", defined as wild birds or mammals hunted for food or sport, a word also used to describe the meat of these when eaten. Chickens are medium-sized, chunky birds with an upright stance and characterised by fleshy red combs and wattles on their heads. Males, known as cocks, are usually larger, more boldly coloured, and have more exaggerated plumage than females (hens). Chickens are gregarious, omnivorous , ground-dwelling birds that in their natural surroundings search among the leaf litter for seeds, invertebrates, and other small animals. They seldom fly except as a result of perceived danger, preferring to run into the undergrowth if approached. Today's domestic chicken ( Gallus gallus domesticus ) is mainly descended from the wild red junglefowl of Asia, with some additional input from grey junglefowl , Sri Lankan junglefowl , and green junglefowl . Genomic studies estimate that the chicken was domesticated 8,000 years ago in Southeast Asia and spread to China and India 2000–3000 years later. Archaeological evidence supports domestic chickens in Southeast Asia well before 6000 BC, China by 6000 BC and India by 2000 BC. A landmark 2020 Nature study that fully sequenced 863 chickens across the world suggests that all domestic chickens originate from a single domestication event of red junglefowl whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. These domesticated chickens spread across Southeast and South Asia where they interbred with local wild species of junglefowl, forming genetically and geographically distinct groups. Analysis of the most popular commercial breed shows that the White Leghorn breed possesses a mosaic of divergent ancestries inherited from subspecies of red junglefowl. Chickens were one of the domesticated animals carried with the sea-borne Austronesian migrations into Taiwan , Island Southeast Asia , Island Melanesia , Madagascar , and the Pacific Islands ; starting from around 3500 to 2500 BC. By 2000 BC, chickens seem to have reached the Indus Valley and 250 years later, they arrived in Egypt. They were still used for fighting and were regarded as symbols of fertility. The Romans used them in divination , and the Egyptians made a breakthrough when they learned the difficult technique of artificial incubation . Since then, the keeping of chickens has spread around the world for the production of food with the domestic fowl being a valuable source of both eggs and meat. Since their domestication, a large number of breeds of chickens have been established, but with the exception of the white Leghorn , most commercial birds are of hybrid origin. In about 1800, chickens began to be kept on a larger scale, and modern high-output poultry farms were present in the United Kingdom from around 1920 and became established in the United States soon after the Second World War . By the mid-20th century, the poultry meat-producing industry was of greater importance than the egg-laying industry. Poultry breeding has produced breeds and strains to fulfil different needs; light-framed, egg-laying birds that can produce 300 eggs a year; fast-growing, fleshy birds destined for consumption at a young age, and utility birds which produce both an acceptable number of eggs and a well-fleshed carcase. Male birds are unwanted in the egg-laying industry and can often be identified as soon as they are hatch for subsequent culling. In meat breeds, these birds are sometimes castrated (often chemically) to prevent aggression. The resulting bird, called a capon , has more tender and flavorful meat, as well. A bantam is a small variety of domestic chicken, either a miniature version of a member of a standard breed , or a "true bantam" with no larger counterpart. The name derives from the town of Bantam in Java where European sailors bought the local small chickens for their shipboard supplies. Bantams may be a quarter to a third of the size of standard birds and lay similarly small eggs. They are kept by small-holders and hobbyists for egg production, use as broody hens, ornamental purposes, and showing. Cockfighting is said to be the world's oldest spectator sport. Two mature males (cocks or roosters) are set to fight each other, and will do so with great vigour until one is critically injured or killed. Cockfighting is extremely widespread in Island Southeast Asia , and often had ritual significance in addition to being a gambling sport. They also formed part of the cultures of ancient India, China, Persia, Greece, Rome, and large sums were won or lost depending on the outcome of an encounter. Breeds such as the Aseel were developed in the Indian subcontinent for their aggressive behaviour. Cockfighting has been banned in many countries during the last century on the grounds of cruelty to animals. Cockfighting is said to be the world's oldest spectator sport. Two mature males (cocks or roosters) are set to fight each other, and will do so with great vigour until one is critically injured or killed. Cockfighting is extremely widespread in Island Southeast Asia , and often had ritual significance in addition to being a gambling sport. They also formed part of the cultures of ancient India, China, Persia, Greece, Rome, and large sums were won or lost depending on the outcome of an encounter. Breeds such as the Aseel were developed in the Indian subcontinent for their aggressive behaviour. Cockfighting has been banned in many countries during the last century on the grounds of cruelty to animals. Ducks are medium-sized aquatic birds with broad bills, eyes on the side of the head, fairly long necks, short legs set far back on the body, and webbed feet. Males, known as drakes, are often larger than females (known as hens) and are differently coloured in some breeds. Domestic ducks are omnivores , eating a variety of animal and plant materials such as aquatic insects, molluscs, worms, small amphibians, waterweeds, and grasses. They feed in shallow water by dabbling, with their heads underwater and their tails upended. Most domestic ducks are too heavy to fly, and they are social birds, preferring to live and move around together in groups. They keep their plumage waterproof by preening, a process that spreads the secretions of the preen gland over their feathers. Clay models of ducks found in China dating back to 4000 BC may indicate the domestication of ducks took place there during the Yangshao culture . Even if this is not the case, domestication of the duck took place in the Far East at least 1500 years earlier than in the West. Lucius Columella , writing in the first century BC, advised those who sought to rear ducks to collect wildfowl eggs and put them under a broody hen, because when raised in this way, the ducks "lay aside their wild nature and without hesitation breed when shut up in the bird pen". Despite this, ducks did not appear in agricultural texts in Western Europe until about 810 AD, when they began to be mentioned alongside geese, chickens, and peafowl as being used for rental payments made by tenants to landowners. It is widely agreed that the mallard ( Anas platyrhynchos ) is the ancestor of all breeds of domestic duck (with the exception of the Muscovy duck ( Cairina moschata ), which is not closely related to other ducks). Ducks are farmed mainly for their meat, eggs, and down . As is the case with chickens, various breeds have been developed, selected for egg-laying ability, fast growth, and a well-covered carcase. The most common commercial breed in the United Kingdom and the United States is the Pekin duck , which can lay 200 eggs a year and can reach a weight of 3.5 kg (7 lb 11 oz) in 44 days. In the Western world , ducks are not as popular as chickens, because the latter produce larger quantities of white, lean meat and are easier to keep intensively, making the price of chicken meat lower than that of duck meat. While popular in haute cuisine , duck appears less frequently in the mass-market food industry. However, things are different in the East. Ducks are more popular there than chickens and are mostly still herded in the traditional way and selected for their ability to find sufficient food in harvested rice fields and other wet environments. The greylag goose ( Anser anser ) was domesticated by the Egyptians at least 3000 years ago, and a different wild species, the swan goose ( Anser cygnoides ), domesticated in Siberia about a thousand years later, is known as a Chinese goose . The two hybridise with each other and the large knob at the base of the beak, a noticeable feature of the Chinese goose, is present to a varying extent in these hybrids. The hybrids are fertile and have resulted in several of the modern breeds. Despite their early domestication, geese have never gained the commercial importance of chickens and ducks. Domestic geese are much larger than their wild counterparts and tend to have thick necks, an upright posture, and large bodies with broad rear ends. The greylag-derived birds are large and fleshy and used for meat, while the Chinese geese have smaller frames and are mainly used for egg production. The fine down of both is valued for use in pillows and padded garments. They forage on grass and weeds, supplementing this with small invertebrates, and one of the attractions of rearing geese is their ability to grow and thrive on a grass-based system. They are very gregarious and have good memories and can be allowed to roam widely in the knowledge that they will return home by dusk. The Chinese goose is more aggressive and noisy than other geese and can be used as a guard animal to warn of intruders. The flesh of meat geese is dark-coloured and high in protein, but they deposit fat subcutaneously, although this fat contains mostly monounsaturated fatty acids . The birds are killed either around 10 or about 24 weeks. Between these ages, problems with dressing the carcase occur because of the presence of developing pin feathers . In some countries, geese and ducks are force-fed to produce livers with an exceptionally high fat content for the production of foie gras . Over 75% of world production of this product occurs in France, with lesser industries in Hungary and Bulgaria and a growing production in China. Foie gras is considered a luxury in many parts of the world, but the process of feeding the birds in this way is banned in many countries on animal welfare grounds. Turkeys are large birds, their nearest relatives being the pheasant and the guineafowl. Males are larger than females and have spreading, fan-shaped tails and distinctive, fleshy wattles , called a snood , that hang from the top of the beak and are used in courtship display. Wild turkeys can fly, but seldom do so, preferring to run with a long, straddling gait. They roost in trees and forage on the ground, feeding on seeds, nuts, berries, grass, foliage, invertebrates, lizards, and small snakes. The modern domesticated turkey is descended from one of six subspecies of wild turkey ( Meleagris gallopavo ) found in the present Mexican states of Jalisco , Guerrero and Veracruz . Pre-Aztec tribes in south-central Mexico first domesticated the bird around 800 BC, and Pueblo Indians inhabiting the Colorado Plateau in the United States did likewise around 200 BC. They used the feathers for robes, blankets, and ceremonial purposes. More than 1,000 years later, they became an important food source. The first Europeans to encounter the bird misidentified it as a guineafowl, a bird known as a "turkey fowl" at that time because it had been introduced into Europe via Turkey. Commercial turkeys are usually reared indoors under controlled conditions. These are often large buildings, purpose-built to provide ventilation and low light intensities (this reduces the birds' activity and thereby increases the rate of weight gain). The lights can be switched on for 24 h/day, or a range of step-wise light regimens to encourage the birds to feed often and therefore grow rapidly. Females achieve slaughter weight at about 15 weeks of age and males at about 19. Mature commercial birds may be twice as heavy as their wild counterparts. Many different breeds have been developed, but the majority of commercial birds are white, as this improves the appearance of the dressed carcass, the pin feathers being less visible. Turkeys were at one time mainly consumed on special occasions such as Christmas (10 million birds in the United Kingdom) or Thanksgiving (60 million birds in the United States). However, they are increasingly becoming part of the everyday diet in many parts of the world. Guineafowl originated in southern Africa, and the species most often kept as poultry is the helmeted guineafowl ( Numida meleagris ). It is a medium-sized grey or speckled bird with a small naked head with colorful wattles and a knob on top, and was domesticated by the time of the ancient Greeks and Romans. Guineafowl are hardy, sociable birds that subsist mainly on insects, but also consume grasses and seeds. They will keep a vegetable garden clear of pests and will eat the ticks that carry Lyme disease . They happily roost in trees and give a loud vocal warning of the approach of predators. Their flesh and eggs can be eaten in the same way as chickens, young birds being ready for the table at the age of about four months. A squab is the name given to the young of domestic pigeons that are destined for the table. Like other domesticated pigeons, birds used for this purpose are descended from the rock dove ( Columba livia ). Special utility breeds with desirable characteristics are used. Two eggs are laid and incubated for about 17 days. When they hatch, the squabs are fed by both parents on "pigeon's milk", a thick secretion high in protein produced by the crop . Squabs grow rapidly, but are slow to fledge and are ready to leave the nest at 26 to 30 days weighing about 500 g (1 lb 2 oz) . By this time, the adult pigeons will have laid and be incubating another pair of eggs and a prolific pair should produce two squabs every four weeks during a breeding season lasting several months. Worldwide, more chickens are kept than any other type of poultry, with over 50 billion birds being raised each year as a source of meat and eggs. Traditionally, such birds would have been kept extensively in small flocks, foraging during the day and housed at night. This is still the case in developing countries, where the women often make important contributions to family livelihoods through keeping poultry. However, rising world populations and urbanization have led to the bulk of production being in larger, more intensive specialist units. These are often situated close to where the feed is grown or near to where the meat is needed, and result in cheap, safe food being made available for urban communities. Profitability of production depends very much on the price of feed, which has been rising. High feed costs could limit further development of poultry production. In free-range husbandry, the birds can roam freely outdoors for at least part of the day. Often, this is in large enclosures, but the birds have access to natural conditions and can exhibit their normal behaviours. A more intensive system is yarding , in which the birds have access to a fenced yard and poultry house at a higher stocking rate. Poultry can also be kept in a barn system, with no access to the open air, but with the ability to move around freely inside the building. The most intensive system for egg-laying chickens is battery cages , often set in multiple tiers. In these, several birds share a small cage which restricts their ability to move around and behave in a normal manner. The eggs are laid on the floor of the cage and roll into troughs outside for ease of collection. Battery cages for hens have been illegal in the EU since January 1, 2012. Chickens raised intensively for their meat are known as "broilers". Breeds have been developed that can grow to an acceptable carcass size ( 2 kg or 4 lb 7 oz ) in six weeks or less. Broilers grow so fast, their legs cannot always support their weight and their hearts and respiratory systems may not be able to supply enough oxygen to their developing muscles. Mortality rates at 1% are much higher than for less-intensively reared laying birds which take 18 weeks to reach similar weights. Processing the birds is done automatically with conveyor-belt efficiency. They are hung by their feet, stunned, killed, bled, scalded, plucked, have their heads and feet removed, eviscerated, washed, chilled, drained, weighed, and packed, all within the course of little over two hours. Both intensive and free-range farming have animal welfare concerns. In intensive systems, cannibalism , feather pecking and vent pecking can be common, with some farmers using beak trimming as a preventative measure. Diseases can also be common and spread rapidly through the flock. In extensive systems, the birds are exposed to adverse weather conditions and are vulnerable to predators and disease-carrying wild birds. Barn systems have been found to have the worst bird welfare. In Southeast Asia , a lack of disease control in free-range farming has been associated with outbreaks of avian influenza . In many countries, national and regional poultry shows are held where enthusiasts exhibit their birds which are judged on certain phenotypical breed traits as specified by their respective breed standards . The idea of poultry exhibition may have originated after cockfighting was made illegal, as a way of maintaining a competitive element in poultry husbandry. Breed standards were drawn up for egg-laying, meat-type, and purely ornamental birds, aiming for uniformity. Sometimes, poultry shows are part of general livestock shows , and sometimes they are separate events such as the annual "National Championship Show" in the United Kingdom organised by the Poultry Club of Great Britain . Poultry is the second most widely eaten type of meat in the world, accounting for about 30% of total meat production worldwide compared to pork at 38%. Sixteen billion birds are raised annually for consumption, more than half of these in industrialised, factory-like production units. Global broiler meat production rose to 84.6 million tonnes in 2013. The largest producers were the United States (20%), China (16.6%), Brazil (15.1%) and the European Union (11.3%). There are two distinct models of production; the European Union supply chain model seeks to supply products which can be traced back to the farm of origin. This model faces the increasing costs of implementing additional food safety requirements, welfare issues and environmental regulations. In contrast, the United States model turns the product into a commodity. World production of duck meat was about 4.2 million tonnes in 2011 with China producing two thirds of the total, some 1.7 billion birds. Other notable duck-producing countries in the Far East include Vietnam, Thailand, Malaysia, Myanmar, Indonesia and South Korea (12% in total). France (3.5%) is the largest producer in the West, followed by other EU nations (3%) and North America (1.7%). China was also by far the largest producer of goose and guinea fowl meat, with a 94% share of the 2.6 million tonne global market. Global egg production was expected to reach 65.5 million tonnes in 2013, surpassing all previous years. Between 2000 and 2010, egg production was growing globally at around 2% per year, but since then growth has slowed down to nearer 1%. In 2018, egg production reached 76.7 million tonnes, a huge 24% growth since 2008. Poultry is available fresh or frozen, as whole birds or as joints (cuts), bone-in or deboned, seasoned in various ways, raw or ready cooked. The meatiest parts of a bird are the flight muscles on its chest, called "breast" meat, and the walking muscles on the legs , called the "thigh" and "drumstick". The wings are also eaten ( Buffalo wings are a popular example in the United States) and may be split into three segments, the meatier "drumette", the "wingette" (also called the "flat"), and the wing tip (also called the "flapper"). In Japan, the wing is frequently separated, and these parts are referred to as æ‰‹ç¾½å ƒ ( teba-moto "wing base") and æ‰‹ç¾½å ˆ ( teba-saki "wing tip"). Dark meat, which avian myologists refer to as "red muscle", is used for sustained activity—chiefly walking, in the case of a chicken. The dark color comes from the protein myoglobin , which plays a key role in oxygen uptake and storage within cells. White muscle, in contrast, is suitable only for short bursts of activity such as, for chickens, flying. Thus, the chicken's leg and thigh meat are dark, while its breast meat (which makes up the primary flight muscles) is white. Other birds with breast muscle more suitable for sustained flight, such as ducks and geese, have red muscle (and therefore dark meat) throughout. Some cuts of meat including poultry expose the microscopic regular structure of intracellular muscle fibrils which can diffract light and produce iridescent colors, an optical phenomenon sometimes called structural coloration . Poultry is the second most widely eaten type of meat in the world, accounting for about 30% of total meat production worldwide compared to pork at 38%. Sixteen billion birds are raised annually for consumption, more than half of these in industrialised, factory-like production units. Global broiler meat production rose to 84.6 million tonnes in 2013. The largest producers were the United States (20%), China (16.6%), Brazil (15.1%) and the European Union (11.3%). There are two distinct models of production; the European Union supply chain model seeks to supply products which can be traced back to the farm of origin. This model faces the increasing costs of implementing additional food safety requirements, welfare issues and environmental regulations. In contrast, the United States model turns the product into a commodity. World production of duck meat was about 4.2 million tonnes in 2011 with China producing two thirds of the total, some 1.7 billion birds. Other notable duck-producing countries in the Far East include Vietnam, Thailand, Malaysia, Myanmar, Indonesia and South Korea (12% in total). France (3.5%) is the largest producer in the West, followed by other EU nations (3%) and North America (1.7%). China was also by far the largest producer of goose and guinea fowl meat, with a 94% share of the 2.6 million tonne global market. Global egg production was expected to reach 65.5 million tonnes in 2013, surpassing all previous years. Between 2000 and 2010, egg production was growing globally at around 2% per year, but since then growth has slowed down to nearer 1%. In 2018, egg production reached 76.7 million tonnes, a huge 24% growth since 2008. Poultry is available fresh or frozen, as whole birds or as joints (cuts), bone-in or deboned, seasoned in various ways, raw or ready cooked. The meatiest parts of a bird are the flight muscles on its chest, called "breast" meat, and the walking muscles on the legs , called the "thigh" and "drumstick". The wings are also eaten ( Buffalo wings are a popular example in the United States) and may be split into three segments, the meatier "drumette", the "wingette" (also called the "flat"), and the wing tip (also called the "flapper"). In Japan, the wing is frequently separated, and these parts are referred to as æ‰‹ç¾½å ƒ ( teba-moto "wing base") and æ‰‹ç¾½å ˆ ( teba-saki "wing tip"). Dark meat, which avian myologists refer to as "red muscle", is used for sustained activity—chiefly walking, in the case of a chicken. The dark color comes from the protein myoglobin , which plays a key role in oxygen uptake and storage within cells. White muscle, in contrast, is suitable only for short bursts of activity such as, for chickens, flying. Thus, the chicken's leg and thigh meat are dark, while its breast meat (which makes up the primary flight muscles) is white. Other birds with breast muscle more suitable for sustained flight, such as ducks and geese, have red muscle (and therefore dark meat) throughout. Some cuts of meat including poultry expose the microscopic regular structure of intracellular muscle fibrils which can diffract light and produce iridescent colors, an optical phenomenon sometimes called structural coloration . As of 2022, no clinical trials have assessed poultry intake on human health. Poultry meat and eggs provide nutritionally beneficial food containing protein of high quality. This is accompanied by low levels of fat which have a favourable mix of fatty acids. Chicken meat contains about two to three times as much polyunsaturated fat as most types of red meat when measured by weight. However, for boneless, skinless chicken breast, the amount is much lower. 100 grams (3.5 oz) of raw chicken breast contains 2 grams (0.071 oz) of fat and 22 grams (0.78 oz) of protein, compared to 9 grams (0.32 oz) of fat and 20 grams (0.71 oz) of protein for the same portion of raw beef flank steak. A 2011 study by the Translational Genomics Research Institute showed that 47% of the meat and poultry sold in United States grocery stores was contaminated with Staphylococcus aureus , and 52% of the bacteria concerned showed resistance to at least three groups of antibiotics. Thorough cooking of the product would kill these bacteria, but a risk of cross-contamination from improper handling of the raw product is still present. Also, some risk is present for consumers of poultry meat and eggs to bacterial infections such as Salmonella and Campylobacter . Poultry products may become contaminated by these bacteria during handling, processing, marketing, or storage, resulting in food-borne illness if the product is improperly cooked or handled. In general, avian influenza is a disease of birds caused by bird-specific influenza A virus that is not normally transferred to people; however, people in contact with live poultry are at the greatest risk of becoming infected with the virus and this is of particular concern in areas such as Southeast Asia, where the disease is endemic in the wild bird population and domestic poultry can become infected. The virus possibly could mutate to become highly virulent and infectious in humans and cause an influenza pandemic . Bacteria can be grown in the laboratory on nutrient culture media, but viruses need living cells in which to replicate. Many vaccines to infectious diseases can be grown in fertilised chicken eggs. Millions of eggs are used each year to generate the annual flu vaccine requirements, a complex process that takes about six months after the decision is made as to what strains of virus to include in the new vaccine. A problem with using eggs for this purpose is that people with egg allergies are unable to be immunised, but this disadvantage may be overcome as new techniques for cell-based rather than egg-based culture become available. Cell-based culture will also be useful in a pandemic when it may be difficult to acquire a sufficiently large quantity of suitable sterile, fertile eggs.

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Avian influenza

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National Avian Influenza Reference Laboratory

The National Avian Influenza Reference Laboratory (NAIRL) is a BSL3 facility in Harbin , China . In October 2019, scientists at the NAIRL reported on the development of a real-time RT-PCR test for the H5N6 virus. On 2 February 2021, the NAIRL reported an outbreak in Yuanmingyuan Ruins Park , Haidian District , Beijing of a highly pathogenic H5N8 variant, which had a mortality rate of 1 in 5 Cygnus atratus (Anatidae) animals.

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Avian influenza

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2024 in Thailand

← → Following is a list of events and scheduled events in the year 2024 in Thailand . The year 2024 is reckoned as the year 2567 in Buddhist Era , the Thai calendar.Source:

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Avian influenza

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Oriental magpie-robin

Gracula saularis Linnaeus, 1758 The Oriental magpie-robin ( Copsychus saularis ) is a small passerine bird that was formerly classed as a member of the thrush family Turdidae , but now considered an Old World flycatcher . They are distinctive black and white birds with a long tail that is held upright as they forage on the ground or perch conspicuously. Occurring across most of the Indian subcontinent and parts of Southeast Asia , they are common birds in urban gardens as well as forests. They are particularly well known for their songs and were once popular as cagebirds. The oriental magpie-robin is considered the national bird of Bangladesh .This species is 19 centimetres (7.5 in) long, including the long tail, which is usually held cocked upright when hopping on the ground. When they are singing a song the tail is normal like other birds. It is similar in shape to the smaller European robin , but is longer-tailed. The male has black upperparts, head and throat apart from a white shoulder patch. The underparts and the sides of the long tail are white. Females are greyish black above and greyish white under. Young birds have scaly brown upperparts and head. The nominate race is found on the Indian subcontinent and the females of this race are the palest. The females of the Andaman Islands race andamanensis are darker, heavier-billed and shorter-tailed. The Sri Lankan race ceylonensis (formerly included with the peninsular Indian populations south of the Kaveri River) and southern nominate individuals have the females nearly identical to the males in shade. The eastern populations, the ones in Bangladesh and Bhutan , have more black on the tail and were formerly named erimelas . The populations in Myanmar (Burma) and further south are named as the race musicus . A number of other races have been named across the range, including prosthopellus (Hong Kong), nesiotes , zacnecus , nesiarchus , masculus , pagiensis , javensis , problematicus , amoenus , adamsi , pluto , deuteronymus and mindanensis . However, many of these are not well-marked and the status of some of them is disputed. Some, like mindanensis , have now been usually recognized as full species (the Philippine magpie-robin ). There is more geographic variation in the plumage of females than in that of the males. It is mostly seen close to the ground, hopping along branches or foraging in leaf-litter on the ground with a cocked tail. Males sing loudly from the top of trees or other high perches during the breeding season. The Indian name of dhyal or dhayal has led to many confusions. It was first used by Eleazar Albin ("dialbird") in 1737 (Suppl. N. H. Birds, i. p. 17, pls. xvii. xviii.), and Levaillant (Ois. d'Afr. iii. p. 50) thought it referred to a sun dial and he called it Cadran . Thomas C. Jerdon wrote (B. India, ii. p. 1l6) that Linnaeus , thinking it had some connection with a sun-dial, called it solaris , by lapsus pennae , saularis. This was, however, identified by Edward Blyth as an incorrect interpretation and that it was a Latinization of the Hindi word saulary which means a "hundred songs". A male bird was sent with this Hindi name from Madras by surgeon Edward Bulkley to James Petiver , who first described the species ( Ray, Synops. Meth. Avium , p. 197). This magpie-robin is a resident breeder in tropical southern Asia from Nepal , Bangladesh , India , Sri Lanka and eastern Pakistan , eastern Indonesia , Thailand , south China , Malaysia , and Singapore . The Oriental magpie-robin is found in open woodland and cultivated areas often close to human habitations.Magpie-robins breed mainly from March to July in India and January to June in south-east Asia. Males sing from high perches during courtship. The display of the male involves puffing up the feathers, raising the bill, fanning the tail and strutting. They nest in tree hollows or niches in walls or building, often adopting nest boxes . They line the cavity with grass. The female is involved in most of the nest building, which happens about a week before the eggs are laid. Four or five eggs are laid at intervals of 24 hours and these are oval and usually pale blue green with brownish speckles that match the color of hay. The eggs are incubated by the female alone for 8 to 14 days. The nests are said to have a characteristic odour. [ citation needed ] Females spend more effort on feeding the young than males. Males are quite aggressive in the breeding season and will defend their territory. They respond to the singing of intruders and even their reflections. Males spend more time on nest defense. Studies of the bird song show dialects with neighbours varying in their songs. The calls of many other species may be imitated as part of their song. This may indicate that birds disperse and are not philopatric. Females may sing briefly in the presence of a male. Apart from their song, they use a range of calls including territorial calls, emergence and roosting calls, threat calls, submissive calls, begging calls and distress calls. The typical mobbing calls is a harsh hissing krshhh . The diet of magpie-robins includes mainly insects and other invertebrates. Although mainly insectivorous, they are known to occasionally take flower nectar, geckos, leeches, centipedes and even fish. They are often active late at dusk. They sometimes bathe in rainwater collected on the leaves of a tree. This species is considered one of " least concern " globally, but in some areas, it is declining. In Singapore, they were common in the 1920s; however, the population there declined in the 1970s, presumably due to competition from introduced common mynas . Poaching for the pet bird trade and habitat changes have also affected them and they are locally protected by law. This species has few avian predators. Several pathogens and parasites have been reported. Avian malaria parasites have been isolated from the species, while H4N3 and H5N1 infection has been noted in a few cases. Parasitic nematodes of the eye have been described. Oriental magpie-robins were widely kept as cage birds for their singing abilities and for fighting in India in the past. They continue to be sold in the pet trade in parts of Southeast Asia. The Oriental magpie-robin is the national bird of Bangladesh, where it is common and known as the doyel or doel (Bengali: দোয়েল ). Professor Kazi Zakir Hossain of Dhaka University proposed to consider the Oriental magpie-robin as the country's national bird. His reasoning behind this was that bird can be seen everywhere in towns and villages across the country. In that context, the Oriental magpie-robin was declared as the national bird of Bangladesh. It is a widely used symbol in Bangladesh, appearing on some currency notes; a landmark in the capital city of Dhaka is referred to as the Doel Chattar (meaning: Doel Square). In Sri Lanka, this bird is called Polkichcha . In southern Thailand , this bird is locally known as Binlha ( Thai : บินหลา — with another related bird, the white-rumped shama ). They are frequently mentioned in contemporary songs.

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Avian influenza

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Pasteurized eggs

Pasteurized eggs are eggs that have been pasteurized in order to reduce the risk of foodborne illness in dishes that are not cooked or are only lightly cooked. They may be sold as liquid egg products or pasteurized in the shell.The 2013 United States Food and Drug Administration Food Code defines regular shell eggs as a potentially hazardous food, i.e., "a food that requires time/temperature control for safety (TCS) to limit pathogenic microorganism growth or toxin formation." All egg products sold in the U.S that are pasteurized due to the risk of foodborne illnesses are done per U.S. Department of Agriculture rules. They also do not allow any egg products to be sold without going through the process of pasteurization. They also do not recommend eating shell eggs that are raw or undercooked due to the possibility that Salmonella bacteria may be present. Because of the risk of foodborne illness caused by Salmonella bacteria that may be present in raw eggs, the U.S. Department of Agriculture requires a safe-handling advisory statement on all packages of raw shell eggs that are not treated to destroy Salmonella as follows: "Safe Handling Instructions: To prevent illness from bacteria: Keep eggs refrigerated, cook eggs until yolks are firm, and cook foods containing eggs thoroughly." The primary risk associated with eggs is foodborne illness caused by Salmonella enteritidis bacteria. Salmonella enteritidis is a dangerous bacterium that can be transferred to humans through ingestion of raw or undercooked eggs. Nearly four out of five Salmonella -related foodborne illness cases share a common vehicle: raw or undercooked shell eggs. Salmonellosis , the illness that a Salmonella infection causes, is characterized by nausea, vomiting, abdominal cramps, diarrhea, fever, and headache. The onset of its symptoms begins between six hours and 72 hours after the consumption of food contaminated with Salmonella bacteria. As few as 15 bacterial cells can cause foodborne illness. While the Centers for Disease Control and Prevention estimate there are one million cases of salmonellosis per year in the US leading to 19,000 hospitalizations and 380 deaths, the U.S. Food and Drug Administration (FDA) estimates that only 79,000 cases each year are the result of consuming eggs contaminated with Salmonella , of which only 30 result in death. In Europe, all hens are required to be vaccinated against salmonellosis. Eggs are not washed (and, in some countries, not refrigerated) since condensation could lead to salmonellosis contamination. In the US, it is important to keep eggs refrigerated since not all hens are vaccinated. The process of pasteurizing eggs also destroys avian flu virus. The 2013 FDA Food Code states that in serving highly susceptible populations (preschool age children; older adults; individuals with compromised immune systems; and individuals who receive meals through custodial care-giving environments such as child or adult day care centers, kidney dialysis centers, hospitals, or nursing homes ): Pasteurized eggs or egg products shall be substituted for raw eggs in the preparation of Foods such as Caesar salad , hollandaise or Béarnaise sauce , mayonnaise , meringue , eggnog , ice cream , egg-fortified beverages and recipes in which more than one egg is broken and the eggs are combined. The FDA Food Code has gained adoption by health jurisdictions throughout the U.S. The primary risk associated with eggs is foodborne illness caused by Salmonella enteritidis bacteria. Salmonella enteritidis is a dangerous bacterium that can be transferred to humans through ingestion of raw or undercooked eggs. Nearly four out of five Salmonella -related foodborne illness cases share a common vehicle: raw or undercooked shell eggs. Salmonellosis , the illness that a Salmonella infection causes, is characterized by nausea, vomiting, abdominal cramps, diarrhea, fever, and headache. The onset of its symptoms begins between six hours and 72 hours after the consumption of food contaminated with Salmonella bacteria. As few as 15 bacterial cells can cause foodborne illness. While the Centers for Disease Control and Prevention estimate there are one million cases of salmonellosis per year in the US leading to 19,000 hospitalizations and 380 deaths, the U.S. Food and Drug Administration (FDA) estimates that only 79,000 cases each year are the result of consuming eggs contaminated with Salmonella , of which only 30 result in death. In Europe, all hens are required to be vaccinated against salmonellosis. Eggs are not washed (and, in some countries, not refrigerated) since condensation could lead to salmonellosis contamination. In the US, it is important to keep eggs refrigerated since not all hens are vaccinated.The process of pasteurizing eggs also destroys avian flu virus. The 2013 FDA Food Code states that in serving highly susceptible populations (preschool age children; older adults; individuals with compromised immune systems; and individuals who receive meals through custodial care-giving environments such as child or adult day care centers, kidney dialysis centers, hospitals, or nursing homes ): Pasteurized eggs or egg products shall be substituted for raw eggs in the preparation of Foods such as Caesar salad , hollandaise or Béarnaise sauce , mayonnaise , meringue , eggnog , ice cream , egg-fortified beverages and recipes in which more than one egg is broken and the eggs are combined. The FDA Food Code has gained adoption by health jurisdictions throughout the U.S. As distinct from whole shell eggs, "egg products" are defined by the U.S. Department of Agriculture (USDA) as "eggs that are removed from their shells for processing." The processing of egg products includes breaking eggs, filtering, mixing, stabilizing, blending, pasteurizing, cooling, freezing or drying, and packaging. This is done at USDA-inspected plants. Egg products include whole eggs, whites, yolks and various blends with or without non-egg ingredients that are processed and pasteurized and may be available in liquid, frozen, and dried forms. This is achieved by heating the products to a specified temperature for a specified period. Pre- separated egg and whole egg products may be used in commercial cooking and baking for saving time or for reducing food waste. In addition, the "potentially hazardous" designation for shell eggs does not apply.According to the U.S. Department of Agriculture, in-shell pasteurized eggs may be used safely without cooking. For example, they may safely be consumed raw (as in raw cookie dough or eggnog ) or in undercooked forms (such as a sunny-side up egg). Many food service and health care providers use these eggs to prevent cross-contamination in their kitchens. By traditional pasteurization methods, heating a raw shell egg to a high enough temperature to achieve pasteurization would also cook the egg. However, beginning in the early 1980s, Dr. James P. Cox and R.W. Duffy Cox of Lynden, Washington, began developing methods to pasteurize shell eggs. In the early 1990s, the Coxes were introduced to L. John Davidson. Davidson recognized the market need and opportunity for a safer egg option for consumers and food operations around the country. Davidson acquired a license agreement on the technology from the Cox Family and formed Pasteurized Egg Corporation to introduce safe egg technology to the consumer marketplace. The process for pasteurizing shell eggs has been patented. Currently, National Pasteurized Eggs Inc. of Lansing, Illinois, owns Dr. Cox's patent to the pasteurization process. Only National Pasteurized Eggs Inc. can provide pasteurized shell eggs produced through these patented processes. The eggs can be found in all U.S. states under the brand Davidson's Safest Choice, introduced in 2003. Pasteurizing eggs in their shells is achieved through a technique that uses precise time and temperature zones within water baths. Pasteurizing eggs in their shells can also be achieved through a process that involves treatment with ozone and reactive oxygen species under high and low pressures, followed by replacement with an inert gas, such as nitrogen . Currently, shell eggs pasteurized using the heating technique are the only commercially available pasteurized eggs. According to the U.S. Department of Agriculture, Shell eggs can be pasteurized by a processor if FDA accepted the process for the destruction of Salmonella. Pasteurized shell eggs are now available at some grocery stores and must be kept refrigerated to retain quality. The equipment to pasteurize shell eggs isn't available for home use, and it is very difficult to pasteurize shell eggs at home without cooking the contents of the egg. After pasteurization, the eggs are coated with food-grade wax to maintain freshness and prevent environmental contamination and stamped with a blue or red "P" in a circle to distinguish them from unpasteurized eggs. Opinion on the quality of pasteurized shell eggs is mixed, and sometimes depends on whether comparisons involve experimental processes or products that are actually on the market. Taste tests noted deficiencies in pasteurized shell eggs experimentally produced via a microwaved pasteurization process (not for commercially available pasteurized shell eggs). Using commercially available pasteurized shell eggs, a San Francisco Chronicle reporter noted a "slight chemical taste" for pasteurized shell eggs, and a Lifescript blogger noted a "barely detectable" flavor and aroma difference and stated the eggs were "worth" their price. Relish magazine states that pasteurized shell eggs "look like real eggs, act like real eggs and taste like real eggs." "Independent taste tests conducted in Good Housekeeping kitchens have not been able to tell any differences between raw and pasteurized eggs," according to Food Safety News , and in two out of three tastings a Chicago Tribune reporter preferred pasteurized eggs flavor over farmers market eggs. According to International Business Times , demand for pasteurized shell eggs within the food service industry is strong because, as of 2008, "states such as California, Iowa, Michigan, Wisconsin and Illinois have adopted the most recent FDA Food Code, in which pasteurized shell eggs shall be substituted for raw eggs to at-risk groups." The FDA Food Code exempts pasteurized shell eggs from the definition of "time/temperature control for safe food." requirement to carry a safe handling advisory statement. The U.S. Department of Agriculture also states, "In-shell pasteurized eggs may be used safely without cooking." By traditional pasteurization methods, heating a raw shell egg to a high enough temperature to achieve pasteurization would also cook the egg. However, beginning in the early 1980s, Dr. James P. Cox and R.W. Duffy Cox of Lynden, Washington, began developing methods to pasteurize shell eggs. In the early 1990s, the Coxes were introduced to L. John Davidson. Davidson recognized the market need and opportunity for a safer egg option for consumers and food operations around the country. Davidson acquired a license agreement on the technology from the Cox Family and formed Pasteurized Egg Corporation to introduce safe egg technology to the consumer marketplace. The process for pasteurizing shell eggs has been patented. Currently, National Pasteurized Eggs Inc. of Lansing, Illinois, owns Dr. Cox's patent to the pasteurization process. Only National Pasteurized Eggs Inc. can provide pasteurized shell eggs produced through these patented processes. The eggs can be found in all U.S. states under the brand Davidson's Safest Choice, introduced in 2003. Pasteurizing eggs in their shells is achieved through a technique that uses precise time and temperature zones within water baths. Pasteurizing eggs in their shells can also be achieved through a process that involves treatment with ozone and reactive oxygen species under high and low pressures, followed by replacement with an inert gas, such as nitrogen . Currently, shell eggs pasteurized using the heating technique are the only commercially available pasteurized eggs. According to the U.S. Department of Agriculture, Shell eggs can be pasteurized by a processor if FDA accepted the process for the destruction of Salmonella. Pasteurized shell eggs are now available at some grocery stores and must be kept refrigerated to retain quality. The equipment to pasteurize shell eggs isn't available for home use, and it is very difficult to pasteurize shell eggs at home without cooking the contents of the egg. After pasteurization, the eggs are coated with food-grade wax to maintain freshness and prevent environmental contamination and stamped with a blue or red "P" in a circle to distinguish them from unpasteurized eggs.Opinion on the quality of pasteurized shell eggs is mixed, and sometimes depends on whether comparisons involve experimental processes or products that are actually on the market. Taste tests noted deficiencies in pasteurized shell eggs experimentally produced via a microwaved pasteurization process (not for commercially available pasteurized shell eggs). Using commercially available pasteurized shell eggs, a San Francisco Chronicle reporter noted a "slight chemical taste" for pasteurized shell eggs, and a Lifescript blogger noted a "barely detectable" flavor and aroma difference and stated the eggs were "worth" their price. Relish magazine states that pasteurized shell eggs "look like real eggs, act like real eggs and taste like real eggs." "Independent taste tests conducted in Good Housekeeping kitchens have not been able to tell any differences between raw and pasteurized eggs," according to Food Safety News , and in two out of three tastings a Chicago Tribune reporter preferred pasteurized eggs flavor over farmers market eggs. According to International Business Times , demand for pasteurized shell eggs within the food service industry is strong because, as of 2008, "states such as California, Iowa, Michigan, Wisconsin and Illinois have adopted the most recent FDA Food Code, in which pasteurized shell eggs shall be substituted for raw eggs to at-risk groups." The FDA Food Code exempts pasteurized shell eggs from the definition of "time/temperature control for safe food." requirement to carry a safe handling advisory statement. The U.S. Department of Agriculture also states, "In-shell pasteurized eggs may be used safely without cooking."

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Avian influenza

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Robert Webster (virologist)

Robert Gordon Webster (b. 1932) is an avian influenza authority who correctly posited that pandemic strains of flu arise from genes in flu virus strains in nonhumans; for example, via a reassortment of genetic segments ( antigenic shift ) between viruses in humans and nonhumans (especially birds ) rather than by mutations ( antigenic drift ) in annual human flu strains. Robert Webster was born on 5 July 1932 in Balclutha, New Zealand , and grew up on a farm. He studied microbiology on leaving school, gaining his BSc from University of Otago, New Zealand in 1955, his MSc at the same university in 1957, and his PhD from the Australian National University , Canberra , Australia , in 1962. He worked as a virologist with the New Zealand Department of Agriculture in 1958 - 1959 before being appointed research fellow at the Department of Microbiology at ANU's John Curtin Medical School, for 1964 - 1966. He moved to U.S. in 1969 where he became a member of both the Department of Microbiology and the Department of Immunology at the St. Jude Children's Research Hospital in Memphis, Tennessee , a city where he has lived ever since and has held many research posts.Webster holds the Rose Marie Thomas Chair in Virology at St. Jude Children's Research Hospital. He is also director of the World Health Organization Collaborating Center on the Ecology of Influenza Viruses in Lower Animals and Birds, the world's only laboratory designed to study influenza at the animal-human interface. He is a Fellow of the Royal Society of London, the Royal Society of Medicine and the Royal Society of New Zealand, and a member of the National Academy of Sciences of the United States. In December 2002, he was presented with the Bristol-Myers Squibb Award for Distinguished Achievement in Infectious Diseases Research. Webster has been awarded membership of the National Academy of Sciences of the United States of America , and has been named a fellow of the Royal Society Te Apārangi and the Royal Society of London . He is also a member of the American Society for Microbiology , American Society for Virology , and the American Association for the Advancement of Science , and is a fellow of the Royal Society of Medicine. He heads the World Health Organization (WHO) collaborating laboratory on animal influenza. [ citation needed ]Webster's major discoveries relating to influenza include the likelihood that avians were most likely the culprit in other flu outbreaks. His work is also responsible for the method of human influenza vaccination that is commonly used. Before Webster and his colleagues separated the influenza virus into different particles, the entire influenza virus was injected into a patient as a vaccine - now, only certain parts of the virus are used to create the same response, lessening side effects of the vaccine. Webster's work with the avian flu began after a beach walk with fellow researcher Graeme Laver, on which the men noticed a large number of dead birds along the shoreline. Webster wondered whether it was possible that the birds had died from the avian flu, and subsequently traveled to an island to take samples from hundreds of birds. This led to more trips, and eventually Webster discovered a link between the avian flu and the human flu. He deduced that it is possible for the avian and human viruses to combine, creating a new virus that humans would have no antibodies to. In an interview with NBC, he said that when he first proposed this link, few paid attention to what he saw as a great danger. However, Webster theorizes that the only event that has to occur to begin a flu pandemic is the mixing of avian and human flu strains in the same mammalian cell - most likely in a pig. Pigs are similar enough in genetic makeup to humans that they are susceptible to the human flu; also, in many areas, pigs come in close contact with chickens or ducks, making it likely that they will catch the avian flu. Another danger that Webster has uncovered is the duck. Ducks, while capable of catching and transmitting the avian flu virus through contact with chickens, seldom sicken and die from the exposure. Being alive and quite healthy, the ducks are then capable of spreading the virus to other areas.

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Avian influenza

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Emergent virus

An emergent virus (or emerging virus ) is a virus that is either newly appeared , notably increasing in incidence / geographic range or has the potential to increase in the near future. Emergent viruses are a leading cause of emerging infectious diseases and raise public health challenges globally, given their potential to cause outbreaks of disease which can lead to epidemics and pandemics . As well as causing disease , emergent viruses can also have severe economic implications. Recent examples include the SARS-related coronaviruses , which have caused the 2002–2004 outbreak of SARS ( SARS-CoV-1 ) and the 2019–2023 pandemic of COVID-19 ( SARS-CoV-2 ). Other examples include the human immunodeficiency virus , which causes HIV/AIDS ; the viruses responsible for Ebola ; the H5N1 influenza virus responsible for avian influenza ; and H1N1/09 , which caused the 2009 swine flu pandemic (an earlier emergent strain of H1N1 caused the 1918 Spanish flu pandemic). Viral emergence in humans is often a consequence of zoonosis , which involves a cross-species jump of a viral disease into humans from other animals. As zoonotic viruses exist in animal reservoirs , they are much more difficult to eradicate and can therefore establish persistent infections in human populations. Emergent viruses should not be confused with re-emerging viruses or newly detected viruses. A re-emerging virus is generally considered to be a previously appeared virus that is experiencing a resurgence, for example measles . A newly detected virus is a previously unrecognized virus that had been circulating in the species as endemic or epidemic infections. Newly detected viruses may have escaped classification because they left no distinctive clues and/or could not be isolated or propagated in cell culture . Examples include human rhinovirus (a leading cause of common colds which was first identified in 1956), hepatitis C (eventually identified in 1989), and human metapneumovirus (first described in 2001, but thought to have been circulating since the 19th century). As the detection of such viruses is technology driven, the number reported is likely to expand.Given the rarity of spontaneous development of new virus species, the most frequent cause of emergent viruses in humans is zoonosis . This phenomenon is estimated to account for 73% of all emerging or re-emerging pathogens , with viruses playing a disproportionately large role. RNA viruses are particularly frequent, accounting for 37% of emerging and re-emerging pathogens. A broad range of animals — including wild birds, rodents, and bats — are associated with zoonotic viruses. It is not possible to predict specific zoonotic events that may be associated with a particular animal reservoir at any given time. Zoonotic spillover can either result in self-limited 'dead-end' infections, in which no further human-to-human transmission occurs (as with the rabies virus ), or in infectious cases, in which the zoonotic pathogen is able to sustain human-to-human transmission (as with the Ebola virus ). If the zoonotic virus is able to maintain successful human-to-human transmission, an outbreak may occur. Some spillover events can also result in the virus adapting exclusively for human infection (as occurred with the HIV virus ), in which case humans become a new reservoir for the pathogen. A successful zoonotic 'jump' depends on human contact with an animal harboring a virus variant that is able to infect humans. In order to overcome host-range restrictions and sustain efficient human-to-human transmission, viruses originating from an animal reservoir will normally undergo mutation , genetic recombination , and reassortment . Due to their rapid replication and high mutation rates, RNA viruses are more likely to successfully adapt for invasion of a new host population. While bats are essential members of many ecosystems, they are also frequently implicated as frequent sources of emerging virus infections. Their immune systems have evolved in such a way as to suppress any inflammatory response to viral infections, thereby allowing them to become tolerant hosts for evolving viruses, and consequently provide major reservoirs of zoonotic viruses. They are associated with more zoonotic viruses per host species than any other mammal, and molecular studies have demonstrated that they are the natural hosts for several high-profile zoonotic viruses, including severe acute respiratory syndrome – related coronaviruses and Ebola / Marburg hemorrhagic fever filoviruses. In terms of their potential for spillover events, bats have taken over the leading role previously assigned to rodents. Viruses can be transmitted from bats via several mechanisms, including bites, aerosolization of saliva (e.g., during echolocation ), and feces/urine. Due to their distinct ecology /behavior, bats are naturally more susceptible to viral infection and transmission. Several bat species (e.g., brown bats) aggregate in crowded roosts, which promotes intra- and interspecies viral transmission. Moreover, as bats are widespread in urban areas, humans occasionally encroach on their habitats which are contaminated with guano and urine. Their ability to fly and migration patterns also means that bats are able to spread disease over a large geographic area, while also acquiring new viruses. Additionally, bats experience persistent viral infections which, together with their extreme longevity (some bat species have lifespans of 35 years), helps to maintain viruses and transmit them to other species. Other bat characteristics which contribute to their potency as viral hosts include: their food choices, torpor / hibernation habits, and susceptibility to reinfection. While bats are essential members of many ecosystems, they are also frequently implicated as frequent sources of emerging virus infections. Their immune systems have evolved in such a way as to suppress any inflammatory response to viral infections, thereby allowing them to become tolerant hosts for evolving viruses, and consequently provide major reservoirs of zoonotic viruses. They are associated with more zoonotic viruses per host species than any other mammal, and molecular studies have demonstrated that they are the natural hosts for several high-profile zoonotic viruses, including severe acute respiratory syndrome – related coronaviruses and Ebola / Marburg hemorrhagic fever filoviruses. In terms of their potential for spillover events, bats have taken over the leading role previously assigned to rodents. Viruses can be transmitted from bats via several mechanisms, including bites, aerosolization of saliva (e.g., during echolocation ), and feces/urine. Due to their distinct ecology /behavior, bats are naturally more susceptible to viral infection and transmission. Several bat species (e.g., brown bats) aggregate in crowded roosts, which promotes intra- and interspecies viral transmission. Moreover, as bats are widespread in urban areas, humans occasionally encroach on their habitats which are contaminated with guano and urine. Their ability to fly and migration patterns also means that bats are able to spread disease over a large geographic area, while also acquiring new viruses. Additionally, bats experience persistent viral infections which, together with their extreme longevity (some bat species have lifespans of 35 years), helps to maintain viruses and transmit them to other species. Other bat characteristics which contribute to their potency as viral hosts include: their food choices, torpor / hibernation habits, and susceptibility to reinfection. While bats are essential members of many ecosystems, they are also frequently implicated as frequent sources of emerging virus infections. Their immune systems have evolved in such a way as to suppress any inflammatory response to viral infections, thereby allowing them to become tolerant hosts for evolving viruses, and consequently provide major reservoirs of zoonotic viruses. They are associated with more zoonotic viruses per host species than any other mammal, and molecular studies have demonstrated that they are the natural hosts for several high-profile zoonotic viruses, including severe acute respiratory syndrome – related coronaviruses and Ebola / Marburg hemorrhagic fever filoviruses. In terms of their potential for spillover events, bats have taken over the leading role previously assigned to rodents. Viruses can be transmitted from bats via several mechanisms, including bites, aerosolization of saliva (e.g., during echolocation ), and feces/urine. Due to their distinct ecology /behavior, bats are naturally more susceptible to viral infection and transmission. Several bat species (e.g., brown bats) aggregate in crowded roosts, which promotes intra- and interspecies viral transmission. Moreover, as bats are widespread in urban areas, humans occasionally encroach on their habitats which are contaminated with guano and urine. Their ability to fly and migration patterns also means that bats are able to spread disease over a large geographic area, while also acquiring new viruses. Additionally, bats experience persistent viral infections which, together with their extreme longevity (some bat species have lifespans of 35 years), helps to maintain viruses and transmit them to other species. Other bat characteristics which contribute to their potency as viral hosts include: their food choices, torpor / hibernation habits, and susceptibility to reinfection. Viral emergence is often a consequence of both nature and human activity . In particular, ecological changes can greatly facilitate the emergence and re-emergence of zoonotic viruses. Factors such as deforestation , reforestation , habitat fragmentation , and irrigation can all impact the ways in which humans come into contact with wild animal species and consequently promote virus emergence. In particular, habitat loss of reservoir host species plays a significant role in emerging zoonoses . Additionally, climate change can affect ecosystems and vector distribution, which in turn can affect the emergence of vector-borne viruses. Other ecological changes — for example, species introduction and predator loss — can also affect virus emergence and prevalence. Some agricultural practices — for example, livestock intensification and inappropriate management/disposal of farm animal feces — are also associated with an increased risk of zoonosis. Viruses may also emerge due to the establishment of human populations that are vulnerable to infection. For example, a virus may emerge following loss of cross-protective immunity , which may occur due to loss of a wild virus or termination of vaccination program. Well-developed countries also have higher proportions of aging citizens and obesity-related disease , thus meaning that their populations may be more immunosuppressed and therefore at risk of infection. Contrastingly, poorer nations may have immunocompromised populations due to malnutrition or chronic infection; these countries are also unlikely to have stable vaccination program. Additionally, changes in human demographics — for example, the birth and/or migration of immunologically naïve individuals — can lead to the development of a susceptible population that enables large-scale virus infection. Other factors which can promote viral emergence include globalization ; in particular, international trade and human travel/ migration can result in the introduction of viruses into new areas. Moreover, as densely populated cities promote rapid pathogen transmission, uncontrolled urbanization (i.e., the increased movement and settling of individuals in urban areas ) can promote viral emergence. Animal migration can also lead to the emergence of viruses, as was the case for the West Nile virus which was spread by migrating bird populations. Additionally, human practices regarding food production and consumption can also contribute to the risk of viral emergence. In particular, wet markets (i.e., live animal markets) are an ideal environment for virus transfer, due to the high density of people and wild/farmed animals present. Consumption of bushmeat is also associated with pathogen emergence. Control and prevention of zoonotic diseases depends on appropriate global surveillance at various levels, including identification of novel pathogens, public health surveillance (including serological surveys ), and analysis of the risks of transmission. The complexity of zoonotic events around the world predicates a multidisciplinary approach to prevention. The One Health Model has been proposed as a global strategy to help prevent the emergence of zoonotic diseases in humans, including novel viral diseases. The One Health concept aims to promote the health of animals, humans, and the environment, both locally and globally, by fostering understanding and collaboration between practitioners of different interrelated disciplines, including wildlife biology , veterinary science , medicine , agriculture , ecology , microbiology , epidemiology , and biomedical engineering . As hosts are immunologically naïve to pathogens they have not encountered before, emergent viruses are often extremely virulent in terms of their capacity to cause disease. Their high virulence is also due to a lack of adaptation to the new host; viruses normally exert strong selection pressure on the immune systems of their natural hosts, which in turn exerts a strong selection pressure on viruses. This coevolution means that the natural host is able to manage infection. However, when the virus jumps to a new host (e.g., humans), the new host is unable to deal with infection due to a lack of coevolution, which results in mismatch between host immunoeffectors and virus immunomodulators . [ citation needed ] Additionally, in order to maximize transmission, viruses often naturally undergo attenuation (i.e., virulence is reduced) so that infected animals can survive long enough to infect other animals more efficiently. However, as attenuation takes time to achieve, new host populations will not initially benefit from this phenomenon. Moreover, as zoonotic viruses also naturally exist in animal reservoirs , their survival is not dependent on transmission between new hosts; this means that emergent viruses are even more unlikely to attenuate for the purpose of maximal transmission, and they remain virulent. [ citation needed ] Although emergent viruses are frequently highly virulent, they are limited by several host factors including: innate immunity , natural antibodies , and receptor specificity . If the host has previously been infected by a pathogen that is similar to the emergent virus, the host may also benefit from cross-protective immunity . [ citation needed ]Influenza is a highly contagious respiratory infection, which affects approximately 9% of the global population and causes 300,000 to 500,000 deaths annually. Based on their core proteins, influenza viruses are classified into types A, B, C, and D. While both influenza A and B can cause epidemics in humans, influenza A also has pandemic potential and a higher mutation rate and is therefore most significant to public health. Influenza A viruses are further classified into subtypes, based on the combinations of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). The primary natural reservoir for most influenza A subtypes are wild aquatic birds; however, through a series of mutations, a small subset of these viruses have adapted for infection of humans (and other animals). A key determinant of whether a particular influenza A subtype can infect humans is its binding specificity. Avian influenza A preferentially binds to cell surface receptors with a terminal α2,3‐linked sialic acid , while human influenza A preferentially binds to cell surface receptors with a terminal α2,6‐linked sialic acid. Via mutation, some avian influenza A viruses have successfully altered their binding specificity from α2,3‐ to α2,6‐linked sialic acid. However, in order to emerge in humans, avian influenza A viruses must also adapt their RNA polymerases for function in mammalian cells, as well as mutating for stability in the acidic respiratory tract of humans. Following adaptation and host switch , influenza A viruses have the potential to cause epidemics and pandemics in humans. Minor changes in HA and NA structure ( antigenic drift ) occur frequently, which enables the virus to cause repetitive outbreaks (i.e., seasonal influenza ) by evading immune recognition. Major changes in HA and NA structure ( antigenic shift ), which are caused by genetic reassortment between different influenza A subtypes (e.g., between human and animal subtypes), can instead cause large regional/global pandemics . Due to the emergence of antigenically different influenza A strains in humans, four influenza pandemics occurred in the 20th century alone. Additionally, although animal influenza A viruses (e.g., swine influenza ) are distinct from human influenza viruses, they can still cause zoonotic infection in humans. These infections are largely acquired following direct contact with infected animals or contaminated environments, but do not result in efficient human-to-human transmission; examples of this include H5N1 influenza and H7N9 influenza . In 2002, a highly pathogenic SARS-CoV (severe acute respiratory syndrome coronavirus) strain emerged from a zoonotic reservoir; approximately 8,000 people were infected worldwide, and mortality rates approached 50% or more in the elderly. As SARS-CoV-1 is most contagious post-symptoms, the introduction of strict public health measures effectively halted the epidemic. The natural reservoir host for SARS-CoV-1 is thought to be horseshoe bats , although the virus has also been identified in several small carnivores (e.g., palm civets and racoon dogs ). The emergence of SARS-CoV-1 is believed to have been facilitated by Chinese wet markets, in which civets positive for the virus acted as intermediate hosts and passed SARS-CoV-1 onto humans (and other species). However, more recent analysis suggests that SARS-CoV-1 may have directly jumped from bats to humans, with subsequent cross-transmission between humans and civets. In order to infect cells, SARS-CoV-1 uses the spike surface glycoprotein to recognize and bind to host ACE-2 , which it uses as a cellular entry receptor; the development of this characteristic was crucial in enabling SARS-CoV-1 to 'jump' from bats to other species. First reported in 2012, MERS-CoV (Middle East respiratory syndrome coronavirus) marks the second known introduction of a highly pathogenic coronavirus from a zoonotic reservoir into humans. The case mortality rate of this emergent virus is approximately 35%, with 80% of all cases reported by Saudi Arabia. Although MERS-CoV is likely to have originated in bats, dromedary camels have been implicated as probable intermediate hosts. MERS-CoV is believed to have been circulating in these mammals for over 20 years, and it is thought that novel camel farming practices drove the spillover of MERS-CoV into humans. Studies have shown that humans can be infected with MERS-CoV via direct or indirect contact within infected dromedary camels, while human-to-human transmission is limited. MERS-CoV gains cellular entry by using a spike surface protein to bind to the host DPP4 surface receptor; the core subdomain of this spike surface protein shares similarities with that of SARS-CoV, but its receptor binding subdomain (RBSD) significantly differs. Bluetongue disease is a non-contagious vector-borne disease caused by bluetongue virus, which affects species of ruminants (particularly sheep ). Climate change has been implicated in the emergence and global spread of this disease, due to its impact on vector distribution. The natural vector of the bluetongue virus is the African midge C. imicola , which is normally limited to Africa and subtropical Asia. However, global warming has extended the geographic range of C. imicola , so that it now overlaps with a different vector ( C. pulcaris or C. obsoletus ) with a much more northward geographic range. This change enabled the bluetongue virus to jump vector, thus causing the northward spread of bluetongue disease into Europe. Influenza is a highly contagious respiratory infection, which affects approximately 9% of the global population and causes 300,000 to 500,000 deaths annually. Based on their core proteins, influenza viruses are classified into types A, B, C, and D. While both influenza A and B can cause epidemics in humans, influenza A also has pandemic potential and a higher mutation rate and is therefore most significant to public health. Influenza A viruses are further classified into subtypes, based on the combinations of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). The primary natural reservoir for most influenza A subtypes are wild aquatic birds; however, through a series of mutations, a small subset of these viruses have adapted for infection of humans (and other animals). A key determinant of whether a particular influenza A subtype can infect humans is its binding specificity. Avian influenza A preferentially binds to cell surface receptors with a terminal α2,3‐linked sialic acid , while human influenza A preferentially binds to cell surface receptors with a terminal α2,6‐linked sialic acid. Via mutation, some avian influenza A viruses have successfully altered their binding specificity from α2,3‐ to α2,6‐linked sialic acid. However, in order to emerge in humans, avian influenza A viruses must also adapt their RNA polymerases for function in mammalian cells, as well as mutating for stability in the acidic respiratory tract of humans. Following adaptation and host switch , influenza A viruses have the potential to cause epidemics and pandemics in humans. Minor changes in HA and NA structure ( antigenic drift ) occur frequently, which enables the virus to cause repetitive outbreaks (i.e., seasonal influenza ) by evading immune recognition. Major changes in HA and NA structure ( antigenic shift ), which are caused by genetic reassortment between different influenza A subtypes (e.g., between human and animal subtypes), can instead cause large regional/global pandemics . Due to the emergence of antigenically different influenza A strains in humans, four influenza pandemics occurred in the 20th century alone. Additionally, although animal influenza A viruses (e.g., swine influenza ) are distinct from human influenza viruses, they can still cause zoonotic infection in humans. These infections are largely acquired following direct contact with infected animals or contaminated environments, but do not result in efficient human-to-human transmission; examples of this include H5N1 influenza and H7N9 influenza . In 2002, a highly pathogenic SARS-CoV (severe acute respiratory syndrome coronavirus) strain emerged from a zoonotic reservoir; approximately 8,000 people were infected worldwide, and mortality rates approached 50% or more in the elderly. As SARS-CoV-1 is most contagious post-symptoms, the introduction of strict public health measures effectively halted the epidemic. The natural reservoir host for SARS-CoV-1 is thought to be horseshoe bats , although the virus has also been identified in several small carnivores (e.g., palm civets and racoon dogs ). The emergence of SARS-CoV-1 is believed to have been facilitated by Chinese wet markets, in which civets positive for the virus acted as intermediate hosts and passed SARS-CoV-1 onto humans (and other species). However, more recent analysis suggests that SARS-CoV-1 may have directly jumped from bats to humans, with subsequent cross-transmission between humans and civets. In order to infect cells, SARS-CoV-1 uses the spike surface glycoprotein to recognize and bind to host ACE-2 , which it uses as a cellular entry receptor; the development of this characteristic was crucial in enabling SARS-CoV-1 to 'jump' from bats to other species.First reported in 2012, MERS-CoV (Middle East respiratory syndrome coronavirus) marks the second known introduction of a highly pathogenic coronavirus from a zoonotic reservoir into humans. The case mortality rate of this emergent virus is approximately 35%, with 80% of all cases reported by Saudi Arabia. Although MERS-CoV is likely to have originated in bats, dromedary camels have been implicated as probable intermediate hosts. MERS-CoV is believed to have been circulating in these mammals for over 20 years, and it is thought that novel camel farming practices drove the spillover of MERS-CoV into humans. Studies have shown that humans can be infected with MERS-CoV via direct or indirect contact within infected dromedary camels, while human-to-human transmission is limited. MERS-CoV gains cellular entry by using a spike surface protein to bind to the host DPP4 surface receptor; the core subdomain of this spike surface protein shares similarities with that of SARS-CoV, but its receptor binding subdomain (RBSD) significantly differs. Bluetongue disease is a non-contagious vector-borne disease caused by bluetongue virus, which affects species of ruminants (particularly sheep ). Climate change has been implicated in the emergence and global spread of this disease, due to its impact on vector distribution. The natural vector of the bluetongue virus is the African midge C. imicola , which is normally limited to Africa and subtropical Asia. However, global warming has extended the geographic range of C. imicola , so that it now overlaps with a different vector ( C. pulcaris or C. obsoletus ) with a much more northward geographic range. This change enabled the bluetongue virus to jump vector, thus causing the northward spread of bluetongue disease into Europe.

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Avian influenza

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Veterinary Laboratories Agency

The Veterinary Laboratories Agency (VLA) was an executive agency of the UK government 's Department for Environment, Food and Rural Affairs (DEFRA). It carried out animal disease surveillance, diagnostic services and veterinary scientific research for government and commercial organisations. It was based in New Haw , though had offices and laboratories around the country, such as in Sutton Bonington . It was both an International Reference Laboratory and the EU Community Reference Laboratory for avian influenza .1894 - The Central Veterinary Laboratory (CVL) is established in a small basement room in Whitehall, London to deal with a swine fever epidemic. 1917 - The Laboratory moves to its current location in Weybridge. The site is still known as Weybridge today, although the postal address is now Addlestone. On 29 June 2010 DEFRA announced that the VLA would be merged with Animal Health . The merger was completed on 1 April 2011, forming the Animal Health and Veterinary Laboratories Agency .

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Avian influenza

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Subclinical infection

A subclinical infection —sometimes called a preinfection or inapparent infection —is an infection by a pathogen that causes few or no signs or symptoms of infection in the host . Subclinical infections can occur in both humans and animals. Depending on the pathogen, which can be a virus or intestinal parasite , the host may be infectious and able to transmit the pathogen without ever developing symptoms; such a host is called an asymptomatic carrier . Many pathogens, including HIV , typhoid fever , and coronaviruses such as COVID-19 spread in their host populations through subclinical infection. Not all hosts of asymptomatic subclinical infections will become asymptomatic carriers. For example, hosts of Mycobacterium tuberculosis bacteria will only develop active tuberculosis in approximately one-tenth of cases; the majority of those infected by Mtb bacteria have latent tuberculosis , a non-infectious type of tuberculosis that does not produce symptoms in individuals with sufficient immune responses . Because subclinical infections often occur without eventual overt sign, in some cases their presence is only identified by microbiological culture or DNA techniques such as polymerase chain reaction (PCR) tests. Many pathogens are transmitted through their host populations by hosts with few or no symptoms, including sexually transmitted infections such as syphilis and genital warts . In other cases, a host may develop more symptoms as the infection progresses beyond its incubation period . These hosts create a natural reservoir of individuals that can transmit a pathogen to other individuals. Because cases often do not come to clinical attention, health statistics frequently are unable to measure the true prevalence of an infection in a population . This prevents accurate modeling of its transmissibility. Some animal pathogens are also transmitted through subclinical infections. The A(H5) and A(H7) strains of avian influenza are divided into two categories: low pathogenicity avian influenza (LPAI) viruses, and highly pathogenic avian influenza (HPAI) viruses. While HPAI viruses have a very high mortality rate for chickens , LPAI viruses are very mild and produce few, if any symptoms; outbreaks in a flock may go undetected without ongoing testing. Wild ducks and other waterfowl are asymptomatic carriers of avian influenza, notably HPAI, and can be infected without showing signs of illness. The prevalence of subclinical HPAI infection in waterfowl has contributed to the international outbreak of highly lethal H5N8 virus that began in early 2020 . Many pathogens are transmitted through their host populations by hosts with few or no symptoms, including sexually transmitted infections such as syphilis and genital warts . In other cases, a host may develop more symptoms as the infection progresses beyond its incubation period . These hosts create a natural reservoir of individuals that can transmit a pathogen to other individuals. Because cases often do not come to clinical attention, health statistics frequently are unable to measure the true prevalence of an infection in a population . This prevents accurate modeling of its transmissibility. Some animal pathogens are also transmitted through subclinical infections. The A(H5) and A(H7) strains of avian influenza are divided into two categories: low pathogenicity avian influenza (LPAI) viruses, and highly pathogenic avian influenza (HPAI) viruses. While HPAI viruses have a very high mortality rate for chickens , LPAI viruses are very mild and produce few, if any symptoms; outbreaks in a flock may go undetected without ongoing testing. Wild ducks and other waterfowl are asymptomatic carriers of avian influenza, notably HPAI, and can be infected without showing signs of illness. The prevalence of subclinical HPAI infection in waterfowl has contributed to the international outbreak of highly lethal H5N8 virus that began in early 2020 . The following pathogens (together with their symptomatic illnesses) are known to be carried asymptomatically , often in a large percentage of the potential host population:

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Avian influenza

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Disease surveillance

Disease surveillance is an epidemiological practice by which the spread of disease is monitored in order to establish patterns of progression. The main role of disease surveillance is to predict, observe, and minimize the harm caused by outbreak , epidemic , and pandemic situations, as well as increase knowledge about which factors contribute to such circumstances. A key part of modern disease surveillance is the practice of disease case reporting . In modern times, reporting incidences of disease outbreaks has been transformed from manual record keeping, to instant worldwide internet communication. The number of cases could be gathered from hospitals – which would be expected to see most of the occurrences – collated, and eventually made public. With the advent of modern communication technology , this has changed dramatically. Organizations like the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) now can report cases and deaths from significant diseases within days – sometimes within hours – of the occurrence. Further, there is considerable public pressure to make this information available quickly and accurately. [ failed verification ]Formal reporting of notifiable infectious diseases is a requirement placed upon health care providers by many regional and national governments, and upon national governments by the World Health Organization to monitor spread as a result of the transmission of infectious agents. Since 1969, WHO has required that all cases of the following diseases be reported to the organization: cholera , plague , yellow fever , smallpox , relapsing fever and typhus . In 2005, the list was extended to include polio and SARS . Regional and national governments typically monitor a larger set of (around 80 in the U.S.) communicable diseases that can potentially threaten the general population. Tuberculosis , HIV , botulism , hantavirus , anthrax , and rabies are examples of such diseases. The incidence counts of diseases are often used as health indicators to describe the overall health of a population. [ citation needed ]The World Health Organization (WHO) is the lead agency for coordinating global response to major diseases. The WHO maintains Websites for a number of diseases and has active teams in many countries where these diseases occur. During the SARS outbreak in early 2004, for example, the Beijing staff of the WHO produced updates every few days for the duration of the outbreak. Beginning in January 2004, the WHO has produced similar updates for H5N1 . These results are widely reported and closely watched. [ citation needed ] WHO's Epidemic and Pandemic Alert and Response (EPR) to detect, verify rapidly and respond appropriately to epidemic-prone and emerging disease threats covers the following diseases: As the lead organization in global public health, the WHO occupies a delicate role in global politics . It must maintain good relationships with each of the many countries in which it is active. As a result, it may only report results within a particular country with the agreement of the country's government. Because some governments regard the release of any information on disease outbreaks as a state secret, this can place the WHO in a difficult position. [ citation needed ] The WHO coordinated International Outbreak Alert and Response is designed to ensure "outbreaks of potential international importance are rapidly verified and information is quickly shared within the Network" but not necessarily by the public; integrate and coordinate "activities to support national efforts" rather than challenge national authority within that nation in order to "respect the independence and objectivity of all partners". The commitment that "All Network responses will proceed with full respect for ethical standards, human rights, national and local laws, cultural sensitivities and tradition" ensures each nation that its security, financial, and other interests will be given full weight. Testing for a disease can be expensive, and distinguishing between two diseases can be prohibitively difficult in many countries. One standard means of determining if a person has had a particular disease is to test for the presence of antibodies that are particular to this disease. In the case of H5N1, for example, there is a low pathogenic H5N1 strain in wild birds in North America that a human could conceivably have antibodies against. It would be extremely difficult to distinguish between antibodies produced by this strain, and antibodies produced by Asian lineage HPAI A(H5N1) . Similar difficulties are common, and make it difficult to determine how widely a disease may have spread. [ citation needed ] There is currently little available data on the spread of H5N1 in wild birds in Africa and Asia. Without such data, predicting how the disease might spread in the future is difficult. Information that scientists and decision makers need to make useful medical products and informed decisions for health care, but currently lack include: [ citation needed ] Surveillance of wild bird populations Cell cultures of particular strains of diseasesSurveillance of H5N1 in humans, poultry, wild birds, cats and other animals remains very weak in many parts of Asia and Africa. Much remains unknown about the exact extent of its spread. [ citation needed ] H5N1 in China is less than fully reported. Blogs have described many discrepancies between official China government announcements concerning H5N1 and what people in China see with their own eyes. Many reports of total H5N1 cases have excluded China due to widespread disbelief in China's official numbers. (See Disease surveillance in China .) "Only half the world's human bird flu cases are being reported to the World Health Organization within two weeks of being detected, a response time that must be improved to avert a pandemic, a senior WHO official said Saturday. Shigeru Omi , WHO's regional director for the Western Pacific, said it is estimated that countries would have only two to three weeks to stamp out, or at least slow, a pandemic flu strain after it began spreading in humans." David Nabarro , chief avian flu coordinator for the United Nations , says avian flu has too many unanswered questions. CIDRAP reported on 25 August 2006 on a new US government Website that allows the public to view current information about testing of wild birds for H5N1 avian influenza, which is part of a national wild-bird surveillance plan that "includes five strategies for early detection of highly pathogenic avian influenza. Sample numbers from three of these will be available on HEDDS : live wild birds, subsistence hunter-killed birds, and investigations of sick and dead wild birds. The other two strategies involve domestic bird testing and environmental sampling of water and wild-bird droppings. [...] A map on the new USGS site shows that, 9327 birds from Alaska have been tested so far this year, with only a few from most other states. Last year, officials tested just 721 birds from Alaska and none from most other states, another map shows. The goal of the surveillance program for 2006 is to collect 75 000 to 100 000 samples from wild birds and 50 000 environmental samples, officials have said".

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Avian influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Sukhna_Lake/html

Sukhna Lake

Sukhna Lake in Chandigarh , India , is a reservoir at the foothills ( Shivalik hills ) of the Himalayas . This 3 km 2 rain fed lake was created in 1958 by damming the Sukhna Choe, a seasonal stream coming down from the Shivalik Hills. Originally, the seasonal flow entered the lake directly, causing heavy siltation . To check the inflow of silt, 25.42 km 2 of land was acquired in the catchment area and put under vegetation. In 1974, the Choe was diverted and made to bypass the lake completely, the lake being fed by three siltation pots, minimizing the silt into the lake itself. The lake was created by Le Corbusier and the Chief Engineer L Verma. To preserve its tranquillity, Corbusier insisted on two things: that it be forbidden for motorboats to circulate in the water, and for vehicular traffic to be prohibited on top of the dam (promenade). The lake is fringed by a golf course to the south, and Nek Chand 's famous Rock Garden of Chandigarh to its west.Sukhna is an inseparable part of the city of Chandigarh . The city planners were deeply attached to the lake. So much so that Pierre Jeanneret 's ashes were immersed in the lake in 1970 at his niece's request. The roof of the 'bandh' or dam has become a favourite promenade. Serious walkers pursue an exercise regime, families enjoy an evening stroll and nature lovers mingle with children on roller skates. Photographers and painters love to capture the scenic beauty of the setting sun or the heavily used monsoon sky, or the early morning mist in winter set amidst the tranquillity of the lake. Even anglers do not leave unrewarded. Sukhna has a membership-based Lake Club with lawns, a gym, indoor games, swimming pools (more than 4), and large tennis courts with both grass and synthetic courts. Boating, rowing, sculling, sailing, kayaking, and water-skiing can be enjoyed throughout the year. The lake, which was the venue for the Asian Rowing Championships, has the longest channel for rowing and yachting events in Asia. Sukhna is a sanctuary for many exotic migratory birds like the Siberian duck, storks and cranes , during the winter months. The lake has been declared a protected national wetland by the Government of India . During summers, there are streams of men, women, and children, from all walks of life offering voluntary service to desilt the lake bed for about three months. This annual ritual has been a regular feature since long ago. Sukhna Lake is the venue for many festive celebrations, too. The most popular is the Mango Festival held during the monsoons when scores of varieties of mangoes are on display. From time to time, time to time festivals featuring specialities from different Indian States are also held here, along with cultural performances.The Mera Chandigarh administration has made a decision not to allow fish more than 30 cm in size in the Sukhna Lake The Chandigarh Administration has finalized a new plan for Sukhna Lake and New Lake in Sector 42 with Rs 2.73 crore which has also been received from Union Government.B.A. The lake is facing serious issues like weed overgrowth, catchment adequacy and silting that are significantly shrinking its size and depth. A project team, under Parasu Ram Mishra , was deployed to address the issue and take remedial measures, which halted the sedimentation, for a while. Additionally, it has become the subject of litigation between Chandigarh and Punjab. Silting has taken its toll and the volume of the lake has been reduced to 56% of its original. The lake is shrinking rapidly due to siltation and lack of inflow. It was initially hoped that the work of desilting could be undertaken in summers at a war footing and dry dredging could be undertaken at a fraction of cost to save Sukhna in the coming years. Unfortunately, the ground realities seem to be different. Due to heavy rain in August and September, Sukhna was filled up again, and flood gates were being opened. In December 2014, there was an Avian Influenza —or commonly known as the Bird Flu scare —that led to a temporary ban on geese to take premises. The scare started after some migrant geese were found dead in the lake. However, the administration took great precautions and the domesticated geese were culled to check an infection. Workers who culled the geese went for a check to be sure that they were safe. The reason behind the death of the geese—whether there is a bird flu scare —remains unknown.

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Avian influenza

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List of mammals that can get H5N1

Although a wide variety of bird species have been shown to contract and spread Influenza A virus subtype H5N1 , from waterfowl to poultry and birds of prey , mammalian infections have been of particular interest to researchers due to their potential to develop mutations that increase the risk of mammal-to-mammal spread and transmission to and among humans. Other influenza strains are common among mammals, including humans, but this list only shows those who have been proven to carry H5N1. In October 2022, mink became the first detected mammal able to engage in mammal-to-mammal spread of H5N1 .

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Avian influenza

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List of human disease case fatality rates

Human infectious diseases may be characterized by their case fatality rate (CFR), the proportion of people diagnosed with a disease who die from it ( cf. mortality rate ). It should not be confused with the infection fatality rate (IFR), the estimated proportion of people infected by a disease-causing agent, including asymptomatic and undiagnosed infections, who die from the disease. IFR cannot be higher than the CFR and is often much lower, but is also much harder to calculate. This data is based on optimally treated patients and exclude isolated cases or minor outbreaks, unless otherwise indicated.

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Pandemic influenza

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Influenza pandemic

An influenza pandemic is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly. Influenza pandemics occur when a new strain of the influenza virus is transmitted to humans from another animal species. Species that are thought to be important in the emergence of new human strains are pigs , chickens and ducks . These novel strains are unaffected by any immunity people may have to older strains of human influenza and can therefore spread extremely rapidly and infect very large numbers of people. Influenza A viruses can occasionally be transmitted from wild birds to other species, causing outbreaks in domestic poultry, and may give rise to human influenza pandemics. The propagation of influenza viruses throughout the world is thought to be in part by bird migrations , though commercial shipments of live bird products might also be implicated, as well as human travel patterns. [ citation needed ] The World Health Organization (WHO) has produced a six-stage classification that describes the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. This starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people, and ends with a pandemic when infections from the new virus have spread worldwide. One strain of virus that may produce a pandemic in the future is a highly pathogenic variation of the H5N1 subtype of influenza A virus . On 11 June 2009, a new strain of H1N1 influenza was declared to be a pandemic (Stage 6) by the WHO after evidence of spreading in the southern hemisphere. The 13 November 2009 worldwide update by the WHO stated that "[a]s of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported [503,536] laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6,250 deaths." Influenza, commonly known as the flu, is an infectious disease of birds and mammals . It was thought to be caused by comets, earthquakes, volcanoes, cosmic dust, the rising and setting of the sun, vapors arising from the air and ground, or a blast from the stars. Now we know that it is caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). In humans, common symptoms of influenza infection are fever, sore throat, muscle pains , severe headache, coughing, and weakness and fatigue . In more serious cases, influenza causes pneumonia , which can be fatal, particularly in young children and the elderly. While sometimes confused with the common cold , influenza is a much more severe disease and is caused by a different type of virus. Although nausea and vomiting can be produced, especially in children, these symptoms are more characteristic of the unrelated gastroenteritis , which is sometimes called "stomach flu" or "24-hour flu." Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings . Influenza can also be transmitted by saliva , nasal secretions , feces, and blood. Healthy individuals can become infected if they breathe in a virus-laden aerosol directly, or if they touch their eyes, nose or mouth after touching any of the aforementioned bodily fluids (or surfaces contaminated with those fluids). Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F) , and indefinitely at very low temperatures (such as lakes in northeast Siberia ). Most influenza strains can be inactivated easily by disinfectants and detergents . Flu spreads around the world in seasonal epidemics. Ten pandemics were recorded before the Spanish flu of 1918. Three influenza pandemics occurred during the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species , so close proximity between humans and animals can promote epidemics. In addition, epidemiological factors, such as the WWI practice of packing soldiers with severe influenza illness into field hospitals while soldiers with mild illness stayed outside on the battlefield, are an important determinant of whether or not a new strain of influenza virus will spur a pandemic. (During the 1918 Spanish flu pandemic, this practice served to promote the evolution of more virulent viral strains over those that produced mild illness.) When it first killed humans in Asia in the 1990s, a deadly avian strain of H5N1 posed a great risk for a new influenza pandemic; however, this virus did not mutate to spread easily between people. [ permanent dead link ] Vaccinations against influenza are most commonly given to high-risk humans in industrialized countries and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine that contains purified and inactivated material from three viral strains. Typically this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective. [ citation needed ]Variants of Influenza A virus are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu virus like); according to their typical host (example Human flu virus); according to their subtype (example H3N2 ); and according to their deadliness (e.g., Low Pathogenic as discussed below). So, a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu. [ citation needed ] Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. Some variants named using this convention are: Avian variants have also sometimes been named according to their deadliness in poultry, especially chickens: Low Pathogenic Avian Influenza (LPAI) Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu The Influenza A virus subtypes are labeled according to an H number (for hemagglutinin ) and an N number (for neuraminidase ). Each subtype virus has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu . Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. "There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but recently two new types were isolated: a new type (H16) was isolated from black-headed gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005." "The other, H17, was isolated from fruit bats caught in Guatemala and reported in the literature in 2013." Some pandemics are relatively minor such as the one in 1957 called Asian flu (1–4 million dead, depending on source). Others have a higher Pandemic Severity Index whose severity warrants more comprehensive social isolation measures. The 1918 pandemic killed tens of millions and sickened hundreds of millions; the loss of this many people in the population caused upheaval and psychological damage to many people. There were not enough doctors, hospital rooms, or medical supplies for the living as they contracted the disease. Dead bodies were often left unburied as few people were available to deal with them. There can be great social disruption as well as a sense of fear. Efforts to deal with pandemics can leave a great deal to be desired because of human selfishness, lack of trust, illegal behavior, and ignorance. For example, in the 1918 pandemic: "This horrific disconnect between reassurances and reality destroyed the credibility of those in authority. People felt they had no one to turn to, no one to rely on, no one to trust." A letter from a physician at one U.S. Army camp in the 1918 pandemic said: It is only a matter of a few hours then until death comes [...]. It is horrible. One can stand it to see one, two or twenty men die, but to see these poor devils dropping like flies [...]. We have been averaging about 100 deaths per day [...]. Pneumonia means in about all cases death [...]. We have lost an outrageous number of Nurses and Drs. It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce [...]. Flu pandemics typically come in waves. The 1889–1890 and 1918–1920 flu pandemics each came in three or four waves of increasing lethality. Within a wave, mortality was greater at the beginning of the wave. Mortality varies widely in a pandemic. In the 1918 pandemic: In U.S. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9.6 percent, for Indian troops 21.9 percent. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population. Flu pandemics typically come in waves. The 1889–1890 and 1918–1920 flu pandemics each came in three or four waves of increasing lethality. Within a wave, mortality was greater at the beginning of the wave. Mortality varies widely in a pandemic. In the 1918 pandemic: In U.S. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9.6 percent, for Indian troops 21.9 percent. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population. A 1921 book lists nine influenza pandemics prior to the 1889–1890 flu, the first in 1510 . A more modern source lists six. The 1889–1890 pandemic, often referred to as the Asiatic flu or Russian flu , killed about 1 million people out of a world population of about 1.5 billion. It was long believed to be caused by an influenza A subtype (most often H2N2), but recent analysis largely brought on by the 2002-2004 SARS outbreak and the COVID-19 pandemic determined the outbreak to be more likely caused by a coronavirus. The 1918 flu pandemic, commonly referred to as the Spanish flu , was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1 . The Spanish flu pandemic lasted from 1918 to 1920. Various estimates say it killed between 17 million and 100 million people This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death , although the Black Death is estimated to have killed over a fifth of the world's population at the time, a significantly higher proportion. This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms . Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera , or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred." The majority of deaths were from bacterial pneumonia , a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung. The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands. The unusually severe disease killed between 10 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%. Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old. This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1920 pandemic is estimated to be between 17 and 100 million people, constituting approximately 1–6% of the world's population. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years . The Asian flu was a category 2 flu pandemic outbreak caused by a strain of H2N2 that originated in China in early 1957, lasting until 1958. The virus originated from a mutation in wild ducks combining with a pre-existing human strain. The virus was first identified in Guizhou in late February; by mid-March it had spread across the entire mainland. It was not until the virus had reached Hong Kong in April, however, that the world was alerted to the unusual situation, when the international press began to report on the outbreak. The World Health Organization was officially informed when the virus arrived in Singapore , which operated the only influenza surveillance laboratory in Southeast Asia , in early May. From that point on, as the virus continued to sweep the region, the WHO remained attuned to the developing outbreak and helped coordinate the global response for the duration of the pandemic. This was the first pandemic to occur during what is considered the "era of modern virology". One significant development since the 1918 pandemic was the identification of the causative agent behind the flu. Later, it was recognized that the influenza virus changes over time, typically only slightly (a process called " antigenic drift "), sometimes significantly enough to result in a new subtype (" antigenic shift "). Within weeks of the report out of Hong Kong, laboratories in the United States , the United Kingdom , and Australia had analyzed the virus and concluded that it was a novel strain of influenza A. Chinese researchers had already come to a similar conclusion in March, but as China was not a member of the WHO nor a part of its network of National Influenza Centers , this information did not reach the rest of the world, a fact which the WHO would lament after the pandemic. The virus swept across the Middle East , Africa , and the Southern Hemisphere in the middle months of the year, causing widespread outbreaks. By the end of September, nearly the entire inhabited world had been infected or at least seeded with the virus. Around this time, extensive epidemics developed in the Northern Hemisphere following the opening of schools, generally peaking in North America and Europe in October. Some countries experienced a second wave in the final months of the year; Japan experienced a particularly severe resurgence in October. Influenza activity had largely subsided by the end of the year and remained apparently low during the first months of 1958, though some countries, such as the United States, experienced another rise in mortality from respiratory disease, of unclear origin. The disease tended to resemble seasonal influenza in its presentation; the WHO described it at the time as "uniformly benign". However, there was the potential for complications, of which there was some variability. Most deaths were a result of bacterial pneumonia, though cases of this condition were attenuated through the use of antibiotics that did not exist in 1918. There were also detailed accounts of fatal primary influenza pneumonia, with no indication of bacterial infection. Those with underlying conditions such as cardiovascular disease were at greater risk of developing these pneumonias; pregnant women were also vulnerable to complications. In general, the elderly experienced the greatest rates of mortality. Estimates of worldwide deaths vary widely depending on the source, ranging from 1 million to 4 million. Mortality in the US has been estimated between 60,000 and 80,000 deaths. Pandemic impact continued over several years in many countries, with Latin America experiencing considerable excess mortality through 1959. Chile experienced notably severe mortality over the course of two waves during this period. This was the most publicized influenza epidemic at the time of its occurrence. As the first pandemic to occur in the context of a global surveillance network, it was also the first time that preparations could be made ahead of an anticipated epidemic. Vaccination efforts were undertaken in some countries such as the US, though it is doubtful how successful such campaigns were with altering the courses of individual epidemics, mainly due to the timing of when the vaccines became widely available and how many people were able to be effectively immunized before the peak. The Hong Kong flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift , in which genes from multiple subtypes reassorted to form a new virus. This pandemic killed an estimated 1–4 million people worldwide. Those over 65 had the greatest death rates. In the US, there were about 100,000 deaths. The 1977 Russian flu was a relatively benign flu pandemic, mostly affecting population younger than the age of 26 or 25. It is estimated that 700,000 people died due to the pandemic worldwide. The cause was H1N1 virus strain, which was not seen after 1957 until its re-appearance in China and the Soviet Union in 1977. Genetic analysis and several unusual characteristics of the pandemic have prompted speculation that the virus was released to the public through a laboratory accident. [ excessive citations ] An epidemic of influenza-like illness of unknown causation occurred in Mexico in March–April 2009 . On 24 April 2009, following the isolation of an A/H1N1 influenza in seven ill patients in the southwest US, the WHO issued a statement on the outbreak of "influenza like illness" that confirmed cases of A/H1N1 influenza had been reported in Mexico, and that 20 confirmed cases of the disease had been reported in the US. The next day, the number of confirmed cases rose to 40 in the US, 26 in Mexico, six in Canada, and one in Spain. The disease spread rapidly through the rest of the spring, and by 3 May, a total of 787 confirmed cases had been reported worldwide. On 11 June 2009, the ongoing outbreak of Influenza A/H1N1, commonly referred to as swine flu, was officially declared by the WHO to be the first influenza pandemic of the 21st century and a new strain of Influenza A virus subtype H1N1 first identified in April 2009. It is thought to be a mutation (reassortment) of four known strains of influenza A virus subtype H1N1: one endemic in humans, one endemic in birds, and two endemic in pigs (swine). The rapid spread of this new virus was likely due to a general lack of pre-existing antibody-mediated immunity in the human population. On 1 November 2009, a worldwide update by the WHO stated that "199 countries and overseas territories/communities have officially reported a total of over 482,300 laboratory confirmed cases of the influenza pandemic H1N1 infection, that included 6,071 deaths." By the end of the pandemic, declared on 10 August 2010, there were more than 18,000 laboratory-confirmed deaths from H1N1. Due to inadequate surveillance and lack of healthcare in many countries, the actual total of cases and deaths was likely much higher than reported. Experts, including the WHO, have since agreed that an estimated 284,500 people were killed by the disease, about 15 times the number of deaths in the initial death toll. The 1889–1890 pandemic, often referred to as the Asiatic flu or Russian flu , killed about 1 million people out of a world population of about 1.5 billion. It was long believed to be caused by an influenza A subtype (most often H2N2), but recent analysis largely brought on by the 2002-2004 SARS outbreak and the COVID-19 pandemic determined the outbreak to be more likely caused by a coronavirus. The 1918 flu pandemic, commonly referred to as the Spanish flu , was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1 . The Spanish flu pandemic lasted from 1918 to 1920. Various estimates say it killed between 17 million and 100 million people This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death , although the Black Death is estimated to have killed over a fifth of the world's population at the time, a significantly higher proportion. This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms . Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera , or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred." The majority of deaths were from bacterial pneumonia , a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung. The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands. The unusually severe disease killed between 10 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%. Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old. This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1920 pandemic is estimated to be between 17 and 100 million people, constituting approximately 1–6% of the world's population. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years . The Asian flu was a category 2 flu pandemic outbreak caused by a strain of H2N2 that originated in China in early 1957, lasting until 1958. The virus originated from a mutation in wild ducks combining with a pre-existing human strain. The virus was first identified in Guizhou in late February; by mid-March it had spread across the entire mainland. It was not until the virus had reached Hong Kong in April, however, that the world was alerted to the unusual situation, when the international press began to report on the outbreak. The World Health Organization was officially informed when the virus arrived in Singapore , which operated the only influenza surveillance laboratory in Southeast Asia , in early May. From that point on, as the virus continued to sweep the region, the WHO remained attuned to the developing outbreak and helped coordinate the global response for the duration of the pandemic. This was the first pandemic to occur during what is considered the "era of modern virology". One significant development since the 1918 pandemic was the identification of the causative agent behind the flu. Later, it was recognized that the influenza virus changes over time, typically only slightly (a process called " antigenic drift "), sometimes significantly enough to result in a new subtype (" antigenic shift "). Within weeks of the report out of Hong Kong, laboratories in the United States , the United Kingdom , and Australia had analyzed the virus and concluded that it was a novel strain of influenza A. Chinese researchers had already come to a similar conclusion in March, but as China was not a member of the WHO nor a part of its network of National Influenza Centers , this information did not reach the rest of the world, a fact which the WHO would lament after the pandemic. The virus swept across the Middle East , Africa , and the Southern Hemisphere in the middle months of the year, causing widespread outbreaks. By the end of September, nearly the entire inhabited world had been infected or at least seeded with the virus. Around this time, extensive epidemics developed in the Northern Hemisphere following the opening of schools, generally peaking in North America and Europe in October. Some countries experienced a second wave in the final months of the year; Japan experienced a particularly severe resurgence in October. Influenza activity had largely subsided by the end of the year and remained apparently low during the first months of 1958, though some countries, such as the United States, experienced another rise in mortality from respiratory disease, of unclear origin. The disease tended to resemble seasonal influenza in its presentation; the WHO described it at the time as "uniformly benign". However, there was the potential for complications, of which there was some variability. Most deaths were a result of bacterial pneumonia, though cases of this condition were attenuated through the use of antibiotics that did not exist in 1918. There were also detailed accounts of fatal primary influenza pneumonia, with no indication of bacterial infection. Those with underlying conditions such as cardiovascular disease were at greater risk of developing these pneumonias; pregnant women were also vulnerable to complications. In general, the elderly experienced the greatest rates of mortality. Estimates of worldwide deaths vary widely depending on the source, ranging from 1 million to 4 million. Mortality in the US has been estimated between 60,000 and 80,000 deaths. Pandemic impact continued over several years in many countries, with Latin America experiencing considerable excess mortality through 1959. Chile experienced notably severe mortality over the course of two waves during this period. This was the most publicized influenza epidemic at the time of its occurrence. As the first pandemic to occur in the context of a global surveillance network, it was also the first time that preparations could be made ahead of an anticipated epidemic. Vaccination efforts were undertaken in some countries such as the US, though it is doubtful how successful such campaigns were with altering the courses of individual epidemics, mainly due to the timing of when the vaccines became widely available and how many people were able to be effectively immunized before the peak. The Hong Kong flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift , in which genes from multiple subtypes reassorted to form a new virus. This pandemic killed an estimated 1–4 million people worldwide. Those over 65 had the greatest death rates. In the US, there were about 100,000 deaths. The 1977 Russian flu was a relatively benign flu pandemic, mostly affecting population younger than the age of 26 or 25. It is estimated that 700,000 people died due to the pandemic worldwide. The cause was H1N1 virus strain, which was not seen after 1957 until its re-appearance in China and the Soviet Union in 1977. Genetic analysis and several unusual characteristics of the pandemic have prompted speculation that the virus was released to the public through a laboratory accident. [ excessive citations ]An epidemic of influenza-like illness of unknown causation occurred in Mexico in March–April 2009 . On 24 April 2009, following the isolation of an A/H1N1 influenza in seven ill patients in the southwest US, the WHO issued a statement on the outbreak of "influenza like illness" that confirmed cases of A/H1N1 influenza had been reported in Mexico, and that 20 confirmed cases of the disease had been reported in the US. The next day, the number of confirmed cases rose to 40 in the US, 26 in Mexico, six in Canada, and one in Spain. The disease spread rapidly through the rest of the spring, and by 3 May, a total of 787 confirmed cases had been reported worldwide. On 11 June 2009, the ongoing outbreak of Influenza A/H1N1, commonly referred to as swine flu, was officially declared by the WHO to be the first influenza pandemic of the 21st century and a new strain of Influenza A virus subtype H1N1 first identified in April 2009. It is thought to be a mutation (reassortment) of four known strains of influenza A virus subtype H1N1: one endemic in humans, one endemic in birds, and two endemic in pigs (swine). The rapid spread of this new virus was likely due to a general lack of pre-existing antibody-mediated immunity in the human population. On 1 November 2009, a worldwide update by the WHO stated that "199 countries and overseas territories/communities have officially reported a total of over 482,300 laboratory confirmed cases of the influenza pandemic H1N1 infection, that included 6,071 deaths." By the end of the pandemic, declared on 10 August 2010, there were more than 18,000 laboratory-confirmed deaths from H1N1. Due to inadequate surveillance and lack of healthcare in many countries, the actual total of cases and deaths was likely much higher than reported. Experts, including the WHO, have since agreed that an estimated 284,500 people were killed by the disease, about 15 times the number of deaths in the initial death toll. "Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1, H1N2 , and H3N2 are the only known Influenza A virus subtypes currently circulating among humans. Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include: "About 52 key genetic changes distinguish avian influenza strains from those that spread easily among people, according to researchers in Taiwan, who analyzed the genes of more than 400 A type flu viruses." "How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict. We have examined sequences from the 1918 strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the 1918 pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses." Highly pathogenic H5N1 avian influenza kills 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are: [ citation needed ] H1N1 is currently endemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu pandemic that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919. Controversy arose in October 2005, after the H1N1 genome was published in the journal, Science . Many fear that this information could be used for bioterrorism . When he compared the 1918 virus with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person. In mid-April 2009, an H1N1 variant appeared in Mexico, with its center in Mexico City. By 26 April the variant had spread widely; with cases reported in Canada, the US, New Zealand, the UK, France, Spain and Israel. On 29 April the WHO raised the worldwide pandemic phase to 5. On 11 June 2009 the WHO raised the worldwide pandemic phase to 6, which means that the H1N1 swine flu has reached pandemic proportions, with nearly 30,000 confirmed cases worldwide. A 13 November 2009 worldwide update by the WHO states that "206 countries and overseas territories/communities have officially reported over 503,536 laboratory confirmed cases of the influenza pandemic H1N1 infection, including 6,250 deaths." The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which an influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths. [ citation needed ] H3N2 is currently endemic in both human and pig populations. It evolved from H2N2 by antigenic shift and caused the Hong Kong flu pandemic that killed up to 750,000. "An early-onset, severe form of influenza A H3N2 made headlines when it claimed the lives of several children in the United States in late 2003." The dominant strain of annual flu in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. [C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host. H7N7 has unusual zoonotic potential. In 2003 in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded. H1N2 is currently endemic in both human and pig populations. The new H1N2 strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the H1N2 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses. In 2014, the CDC adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of pandemics. The PSAF superseded the 2007 linear Pandemic Severity Index, which assumed 30% spread and measured case fatality rate (CFR) to assess the severity and evolution of the pandemic. Historically, measures of pandemic severity were based on the case fatality rate. However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because: Deaths may lag several weeks behind cases, making the case fatality rate an underestimate The total number of cases may not be known, making the case fatality rate an overestimate A single case fatality rate for the entire population may obscure the effect on vulnerable sub-populations, such as children, the elderly, those with chronic conditions, and members of certain racial and ethnic minorities Fatalities alone may not account for the full effects of the pandemic, such as absenteeism or demand on healthcare services To account for the limitations of measuring the case fatality rate alone, the PSAF rates severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. Each dimension can be measured using more than one measure, which are scaled to allow comparison of the different measures.In 2014, the CDC adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of pandemics. The PSAF superseded the 2007 linear Pandemic Severity Index, which assumed 30% spread and measured case fatality rate (CFR) to assess the severity and evolution of the pandemic. Historically, measures of pandemic severity were based on the case fatality rate. However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because: Deaths may lag several weeks behind cases, making the case fatality rate an underestimate The total number of cases may not be known, making the case fatality rate an overestimate A single case fatality rate for the entire population may obscure the effect on vulnerable sub-populations, such as children, the elderly, those with chronic conditions, and members of certain racial and ethnic minorities Fatalities alone may not account for the full effects of the pandemic, such as absenteeism or demand on healthcare services To account for the limitations of measuring the case fatality rate alone, the PSAF rates severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. Each dimension can be measured using more than one measure, which are scaled to allow comparison of the different measures.The World Health Organization (WHO) developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. This included a classification system for assessing the progress of an outbreak. Phases 1–3 correlate with preparedness, including capacity development and response planning activities, while phases 4–6 clearly signal the need for response and mitigation efforts. In February 2020, WHO announced that it no longer uses this six-phase classification model: "For the sake of clarification, WHO does not use the old system of 6 phases—that ranged from phase 1 (no reports of animal influenza causing human infections) to phase 6 (a pandemic)—that some people may be familiar with from H1N1 in 2009." In 2014, the United States Centers for Disease Control and Prevention (CDC) introduced the Pandemic Intervals Framework for assessing influenza outbreaks. It includes two pre-pandemic intervals: - Investigation Recognition and four pandemic intervals, Initiation Acceleration Deceleration Preparation This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations panel. If influenza remains an animal problem with limited human-to-human transmission it is not a pandemic, though it continues to pose a risk. To prevent the situation from progressing to a pandemic, the following short-term strategies have been put forward: [ citation needed ] Culling and vaccinating livestock Vaccinating poultry workers against common flu Limiting travel in areas where the virus is found The rationale for vaccinating poultry workers against common flu is that it reduces the probability of common influenza virus recombining with avian H5N1 virus to form a pandemic strain. Longer-term strategies proposed for regions where highly pathogenic H5N1 is endemic in wild birds have included: The main ways available to tackle a flu pandemic initially are behavioural. Doing so requires a good public health communication strategy and the ability to track public concerns, attitudes and behaviour. For example, the Flu TElephone Survey Template (FluTEST) was developed for the UK Department of Health as a set of questions for use in national surveys during a flu pandemic. The Institute of Medicine has published a number of reports and summaries of workshops on public policy issues related to influenza pandemics. They are collected in Pandemic Influenza: A Guide to Recent Institute of Medicine Studies and Workshops , and some strategies from these reports are included in the list above. Relevant learning from the 2009 flu pandemic in the UK was published in Health Technology Assessment , volume 14, issue 34. Asymptomatic transmission appears to play a small role, but was not well studied by 2009. There are two groups of antiviral drugs available for the treatment and prophylaxis of influenza: neuraminidase inhibitors such as Oseltamivir (trade name Tamiflu) and Zanamivir (trade name Relenza), and adamantanes such as amantadine and rimantadine. Due to the high rate of side effects and risk of antiviral resistance, use of adamantanes to fight influenza is limited. Many nations, as well as the World Health Organization, are working to stockpile antiviral drugs in preparation for a possible pandemic. Oseltamivir is the most commonly sought drug, since it is available in pill form. Zanamivir is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza. Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies. There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus. A vaccine probably would not be available in the initial stages of population infection. To date, there is no known mechanism to develop a vaccine to protect against a virus which does not yet exist. The avian flu virus H5N1 has the potential to mutate into a pandemic strain, but so do other types of flu virus. Once a potential virus is identified and a vaccine is approved, it normally takes five to six months before the vaccine becomes available. The capability to produce vaccines varies widely from country to country; only 19 countries are listed as "influenza vaccine manufacturers" according to the World Health Organization. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine to become immuno-competent. Distribution to and inside countries would probably be problematic. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country. Another concern is whether countries which do not manufacture vaccines themselves, including those where a pandemic strain is likely to originate, will be able to purchase vaccine to protect their population. Cost considerations aside, they fear that the countries with vaccine-manufacturing capability will reserve production to protect their own populations and not release vaccines to other countries until their own population is protected. Indonesia has refused to share samples of H5N1 strains which have infected and killed its citizens until it receives assurances that it will have access to vaccines produced with those samples. So far, it has not received those assurances. However, in September 2009, Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the UK, and the USA agreed to make 10 percent of their H1N1 vaccine supply available to less-developed countries. There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people. Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million. Trials using adjuvants such as alum , AS03 , AS04 or MF59 to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Vaccine research has mostly been focused on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus. [ citation needed ] Since 2009, most vaccine development efforts have been focused on the current pandemic influenza virus H1N1. As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus, and expected the initial vaccine lots to be available within the following month. The World Health Organization (WHO) developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. This included a classification system for assessing the progress of an outbreak. Phases 1–3 correlate with preparedness, including capacity development and response planning activities, while phases 4–6 clearly signal the need for response and mitigation efforts. In February 2020, WHO announced that it no longer uses this six-phase classification model: "For the sake of clarification, WHO does not use the old system of 6 phases—that ranged from phase 1 (no reports of animal influenza causing human infections) to phase 6 (a pandemic)—that some people may be familiar with from H1N1 in 2009." In 2014, the United States Centers for Disease Control and Prevention (CDC) introduced the Pandemic Intervals Framework for assessing influenza outbreaks. It includes two pre-pandemic intervals: - Investigation Recognition and four pandemic intervals, Initiation Acceleration Deceleration Preparation This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations panel. If influenza remains an animal problem with limited human-to-human transmission it is not a pandemic, though it continues to pose a risk. To prevent the situation from progressing to a pandemic, the following short-term strategies have been put forward: [ citation needed ] Culling and vaccinating livestock Vaccinating poultry workers against common flu Limiting travel in areas where the virus is found The rationale for vaccinating poultry workers against common flu is that it reduces the probability of common influenza virus recombining with avian H5N1 virus to form a pandemic strain. Longer-term strategies proposed for regions where highly pathogenic H5N1 is endemic in wild birds have included:The main ways available to tackle a flu pandemic initially are behavioural. Doing so requires a good public health communication strategy and the ability to track public concerns, attitudes and behaviour. For example, the Flu TElephone Survey Template (FluTEST) was developed for the UK Department of Health as a set of questions for use in national surveys during a flu pandemic. The Institute of Medicine has published a number of reports and summaries of workshops on public policy issues related to influenza pandemics. They are collected in Pandemic Influenza: A Guide to Recent Institute of Medicine Studies and Workshops , and some strategies from these reports are included in the list above. Relevant learning from the 2009 flu pandemic in the UK was published in Health Technology Assessment , volume 14, issue 34. Asymptomatic transmission appears to play a small role, but was not well studied by 2009. There are two groups of antiviral drugs available for the treatment and prophylaxis of influenza: neuraminidase inhibitors such as Oseltamivir (trade name Tamiflu) and Zanamivir (trade name Relenza), and adamantanes such as amantadine and rimantadine. Due to the high rate of side effects and risk of antiviral resistance, use of adamantanes to fight influenza is limited. Many nations, as well as the World Health Organization, are working to stockpile antiviral drugs in preparation for a possible pandemic. Oseltamivir is the most commonly sought drug, since it is available in pill form. Zanamivir is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza. Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies. There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus. A vaccine probably would not be available in the initial stages of population infection. To date, there is no known mechanism to develop a vaccine to protect against a virus which does not yet exist. The avian flu virus H5N1 has the potential to mutate into a pandemic strain, but so do other types of flu virus. Once a potential virus is identified and a vaccine is approved, it normally takes five to six months before the vaccine becomes available. The capability to produce vaccines varies widely from country to country; only 19 countries are listed as "influenza vaccine manufacturers" according to the World Health Organization. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine to become immuno-competent. Distribution to and inside countries would probably be problematic. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country. Another concern is whether countries which do not manufacture vaccines themselves, including those where a pandemic strain is likely to originate, will be able to purchase vaccine to protect their population. Cost considerations aside, they fear that the countries with vaccine-manufacturing capability will reserve production to protect their own populations and not release vaccines to other countries until their own population is protected. Indonesia has refused to share samples of H5N1 strains which have infected and killed its citizens until it receives assurances that it will have access to vaccines produced with those samples. So far, it has not received those assurances. However, in September 2009, Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the UK, and the USA agreed to make 10 percent of their H1N1 vaccine supply available to less-developed countries. There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people. Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million. Trials using adjuvants such as alum , AS03 , AS04 or MF59 to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Vaccine research has mostly been focused on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus. [ citation needed ] Since 2009, most vaccine development efforts have been focused on the current pandemic influenza virus H1N1. As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus, and expected the initial vaccine lots to be available within the following month. The main ways available to tackle a flu pandemic initially are behavioural. Doing so requires a good public health communication strategy and the ability to track public concerns, attitudes and behaviour. For example, the Flu TElephone Survey Template (FluTEST) was developed for the UK Department of Health as a set of questions for use in national surveys during a flu pandemic. The Institute of Medicine has published a number of reports and summaries of workshops on public policy issues related to influenza pandemics. They are collected in Pandemic Influenza: A Guide to Recent Institute of Medicine Studies and Workshops , and some strategies from these reports are included in the list above. Relevant learning from the 2009 flu pandemic in the UK was published in Health Technology Assessment , volume 14, issue 34. Asymptomatic transmission appears to play a small role, but was not well studied by 2009. There are two groups of antiviral drugs available for the treatment and prophylaxis of influenza: neuraminidase inhibitors such as Oseltamivir (trade name Tamiflu) and Zanamivir (trade name Relenza), and adamantanes such as amantadine and rimantadine. Due to the high rate of side effects and risk of antiviral resistance, use of adamantanes to fight influenza is limited. Many nations, as well as the World Health Organization, are working to stockpile antiviral drugs in preparation for a possible pandemic. Oseltamivir is the most commonly sought drug, since it is available in pill form. Zanamivir is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza. Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies. There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus.A vaccine probably would not be available in the initial stages of population infection. To date, there is no known mechanism to develop a vaccine to protect against a virus which does not yet exist. The avian flu virus H5N1 has the potential to mutate into a pandemic strain, but so do other types of flu virus. Once a potential virus is identified and a vaccine is approved, it normally takes five to six months before the vaccine becomes available. The capability to produce vaccines varies widely from country to country; only 19 countries are listed as "influenza vaccine manufacturers" according to the World Health Organization. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine to become immuno-competent. Distribution to and inside countries would probably be problematic. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country. Another concern is whether countries which do not manufacture vaccines themselves, including those where a pandemic strain is likely to originate, will be able to purchase vaccine to protect their population. Cost considerations aside, they fear that the countries with vaccine-manufacturing capability will reserve production to protect their own populations and not release vaccines to other countries until their own population is protected. Indonesia has refused to share samples of H5N1 strains which have infected and killed its citizens until it receives assurances that it will have access to vaccines produced with those samples. So far, it has not received those assurances. However, in September 2009, Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the UK, and the USA agreed to make 10 percent of their H1N1 vaccine supply available to less-developed countries. There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people. Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million. Trials using adjuvants such as alum , AS03 , AS04 or MF59 to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Vaccine research has mostly been focused on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus. [ citation needed ] Since 2009, most vaccine development efforts have been focused on the current pandemic influenza virus H1N1. As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus, and expected the initial vaccine lots to be available within the following month. According to The New York Times as of March 2006, "governments worldwide have spent billions planning for a potential influenza pandemic: buying medicines, running disaster drills, [and] developing strategies for tighter border controls" due to the H5N1 threat. [T]he United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Departments of State , Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government. Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness". Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the CDC, the ECDC , the World Health Organization, the European Commission , the National Influenza Centers, and others. [ failed verification ] In September 2005, David Nabarro , a lead UN health official, warned that a bird flu outbreak could happen at any time and had the potential to kill 5–150 million people. The World Health Organization (WHO), believing that the world was closer to another influenza pandemic than it has been any time since 1968, when the last of the 20th century's three pandemics swept the globe, has developed guidelines on pandemic influenza preparedness and response. The March 2005 plan includes guidance on roles and responsibilities in preparedness and response; information on pandemic phases; and recommended actions for before, during, and after a pandemic. "[E]fforts by the federal government to prepare for pandemic influenza at the national level include a $100 million DHHS initiative in 2003 to build U.S. vaccine production. Several agencies within Department of Health and Human Services (DHHS)—including the Office of the Secretary, the Food and Drug Administration (FDA), CDC , and the National Institute of Allergy and Infectious Diseases (NIAID)—are in the process of working with vaccine manufacturers to facilitate production of pilot vaccine lots for both H5N1 and H9N2 strains as well as contracting for the manufacturing of 2 million doses of an H5N1 vaccine. This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic." Each state and territory of the United States has a specific pandemic flu plan which covers avian flu, swine flu (H1N1), and other potential influenza epidemics. The state plans together with a professionally vetted search engine of flu related research, policies, and plans, is available at the current portal: Pandemic Flu Search Archived 18 November 2019 at the Wayback Machine . On 26 August 2004, Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan, which outlined a coordinated national strategy to prepare for and respond to an influenza pandemic. Public comments were accepted for 60 days. In a speech before the United Nations General Assembly on 14 September 2005, President George W. Bush announced the creation of the International Partnership on Avian and Pandemic Influenza . The Partnership brings together nations and international organizations to improve global readiness by: elevating the issue on national agendas; coordinating efforts among donor and affected nations; mobilizing and leveraging resources; increasing transparency in disease reporting and surveillance; and building capacity to identify, contain and respond to a pandemic influenza. On 5 October 2005, Democratic Senators Harry Reid , Evan Bayh , Dick Durbin , Ted Kennedy , Barack Obama , and Tom Harkin introduced the Pandemic Preparedness and Response Act as a proposal to deal with a possible outbreak. On 27 October 2005, the Department of Health and Human Services awarded a $62.5 million contract to Chiron Corporation to manufacture an avian influenza vaccine designed to protect against the H5N1 influenza virus strain. This followed a previous awarded $100 million contract to Sanofi Pasteur , the vaccines business of Sanofi , for avian flu vaccine. In October 2005, Bush urged bird flu vaccine manufacturers to increase their production. On 1 November 2005, Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza. He also submitted a request to Congress for $7.1 billion to begin implementing the plan. The request includes $251 million to detect and contain outbreaks before they spread around the world; $2.8 billion to accelerate development of cell-culture technology; $800 million for development of new treatments and vaccines; $1.519 billion for the Departments of Health and Human Services ( HHS ) and Defense to purchase influenza vaccines; $1.029 billion to stockpile antiviral medications; and $644 million to ensure that all levels of government are prepared to respond to a pandemic outbreak. On 6 March 2006, Mike Leavitt , Secretary of Health and Human Services, said U.S. health agencies are continuing to develop vaccine alternatives that will protect against the evolving avian influenza virus. The U.S. government, bracing for the possibility that migrating birds could carry a deadly strain of bird flu to North America, plans to test nearly eight times as many wild birds starting in April 2006 as have been tested in the past decade. On 8 March 2006, Dr. David Nabarro , senior UN coordinator for avian and human influenza, said that given the flight patterns of wild birds that have been spreading avian influenza (bird flu) from Asia to Europe and Africa, birds infected with the H5N1 virus could reach the Americas within the next six to 12 months. July 5, 2006, ( CIDRAP News) – "In an update on pandemic influenza preparedness efforts, the federal government said last week it had stockpiled enough vaccine against H5N1 avian influenza virus to inoculate about 4 million people and enough antiviral medication to treat about 6.3 million." The Public Health Agency of Canada follows the WHO's categories, but has expanded them. The avian flu scare of 2006 prompted The Canadian Public Health Agency to release an updated Pandemic Influenza Plan for Health Officials. This document was created to address the growing concern over the hazards faced by public health officials when exposed to sick or dying patients. [ citation needed ] Since the Nipah virus outbreak in 1999, the Malaysian Health Ministry have put in place processes to be better prepared to protect the Malaysian population from the threat of infectious diseases. Malaysia was fully prepared during the severe acute respiratory syndrome (SARS) situation (Malaysia was not a SARS-affected country) and the episode of the H5N1 outbreak in 2004. The Malaysian government has developed a National Influenza Pandemic Preparedness Plan (NIPPP) which serves as a time bound guide for preparedness and response plan for influenza pandemic. It provides a policy and strategic framework for a multisectoral response and contains specific advice and actions to be undertaken by the Ministry of Health at the different levels, other governmental departments and agencies and non-governmental organizations to ensure that resources are mobilized and used most efficiently before, during and after a pandemic episode.In September 2005, David Nabarro , a lead UN health official, warned that a bird flu outbreak could happen at any time and had the potential to kill 5–150 million people. The World Health Organization (WHO), believing that the world was closer to another influenza pandemic than it has been any time since 1968, when the last of the 20th century's three pandemics swept the globe, has developed guidelines on pandemic influenza preparedness and response. The March 2005 plan includes guidance on roles and responsibilities in preparedness and response; information on pandemic phases; and recommended actions for before, during, and after a pandemic. "[E]fforts by the federal government to prepare for pandemic influenza at the national level include a $100 million DHHS initiative in 2003 to build U.S. vaccine production. Several agencies within Department of Health and Human Services (DHHS)—including the Office of the Secretary, the Food and Drug Administration (FDA), CDC , and the National Institute of Allergy and Infectious Diseases (NIAID)—are in the process of working with vaccine manufacturers to facilitate production of pilot vaccine lots for both H5N1 and H9N2 strains as well as contracting for the manufacturing of 2 million doses of an H5N1 vaccine. This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic." Each state and territory of the United States has a specific pandemic flu plan which covers avian flu, swine flu (H1N1), and other potential influenza epidemics. The state plans together with a professionally vetted search engine of flu related research, policies, and plans, is available at the current portal: Pandemic Flu Search Archived 18 November 2019 at the Wayback Machine . On 26 August 2004, Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan, which outlined a coordinated national strategy to prepare for and respond to an influenza pandemic. Public comments were accepted for 60 days. In a speech before the United Nations General Assembly on 14 September 2005, President George W. Bush announced the creation of the International Partnership on Avian and Pandemic Influenza . The Partnership brings together nations and international organizations to improve global readiness by: elevating the issue on national agendas; coordinating efforts among donor and affected nations; mobilizing and leveraging resources; increasing transparency in disease reporting and surveillance; and building capacity to identify, contain and respond to a pandemic influenza. On 5 October 2005, Democratic Senators Harry Reid , Evan Bayh , Dick Durbin , Ted Kennedy , Barack Obama , and Tom Harkin introduced the Pandemic Preparedness and Response Act as a proposal to deal with a possible outbreak. On 27 October 2005, the Department of Health and Human Services awarded a $62.5 million contract to Chiron Corporation to manufacture an avian influenza vaccine designed to protect against the H5N1 influenza virus strain. This followed a previous awarded $100 million contract to Sanofi Pasteur , the vaccines business of Sanofi , for avian flu vaccine. In October 2005, Bush urged bird flu vaccine manufacturers to increase their production. On 1 November 2005, Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza. He also submitted a request to Congress for $7.1 billion to begin implementing the plan. The request includes $251 million to detect and contain outbreaks before they spread around the world; $2.8 billion to accelerate development of cell-culture technology; $800 million for development of new treatments and vaccines; $1.519 billion for the Departments of Health and Human Services ( HHS ) and Defense to purchase influenza vaccines; $1.029 billion to stockpile antiviral medications; and $644 million to ensure that all levels of government are prepared to respond to a pandemic outbreak. On 6 March 2006, Mike Leavitt , Secretary of Health and Human Services, said U.S. health agencies are continuing to develop vaccine alternatives that will protect against the evolving avian influenza virus. The U.S. government, bracing for the possibility that migrating birds could carry a deadly strain of bird flu to North America, plans to test nearly eight times as many wild birds starting in April 2006 as have been tested in the past decade. On 8 March 2006, Dr. David Nabarro , senior UN coordinator for avian and human influenza, said that given the flight patterns of wild birds that have been spreading avian influenza (bird flu) from Asia to Europe and Africa, birds infected with the H5N1 virus could reach the Americas within the next six to 12 months. July 5, 2006, ( CIDRAP News) – "In an update on pandemic influenza preparedness efforts, the federal government said last week it had stockpiled enough vaccine against H5N1 avian influenza virus to inoculate about 4 million people and enough antiviral medication to treat about 6.3 million." The Public Health Agency of Canada follows the WHO's categories, but has expanded them. The avian flu scare of 2006 prompted The Canadian Public Health Agency to release an updated Pandemic Influenza Plan for Health Officials. This document was created to address the growing concern over the hazards faced by public health officials when exposed to sick or dying patients. [ citation needed ]Since the Nipah virus outbreak in 1999, the Malaysian Health Ministry have put in place processes to be better prepared to protect the Malaysian population from the threat of infectious diseases. Malaysia was fully prepared during the severe acute respiratory syndrome (SARS) situation (Malaysia was not a SARS-affected country) and the episode of the H5N1 outbreak in 2004. The Malaysian government has developed a National Influenza Pandemic Preparedness Plan (NIPPP) which serves as a time bound guide for preparedness and response plan for influenza pandemic. It provides a policy and strategic framework for a multisectoral response and contains specific advice and actions to be undertaken by the Ministry of Health at the different levels, other governmental departments and agencies and non-governmental organizations to ensure that resources are mobilized and used most efficiently before, during and after a pandemic episode.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Spanish_flu/html

Spanish flu

The 1918–1920 flu pandemic , also known as the Great Influenza epidemic or by the common misnomer Spanish flu , was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus . The earliest documented case was March 1918 in the state of Kansas in the United States, with further cases recorded in France, Germany and the United Kingdom in April. Two years later, nearly a third of the global population, or an estimated 500 million people, had been infected in four successive waves. Estimates of deaths range from 17 million to 50 million, and possibly as high as 100 million, making it one of the deadliest pandemics in history . The pandemic broke out near the end of World War I , when wartime censors in the belligerent countries suppressed bad news to maintain morale , but newspapers freely reported the outbreak in neutral Spain , creating a false impression of Spain as the epicenter and leading to the "Spanish flu" misnomer. Limited historical epidemiological data make the pandemic's geographic origin indeterminate, with competing hypotheses on the initial spread. Most influenza outbreaks disproportionately kill the young and old, with a higher survival rate in-between, but this pandemic had unusually high mortality for young adults. Scientists offer several explanations for the high mortality, including a six-year climate anomaly affecting migration of disease vectors with increased likelihood of spread through bodies of water. The virus was particularly deadly because it triggered a cytokine storm , ravaging the stronger immune system of young adults, although the viral infection was apparently no more aggressive than previous influenza strains. However, the claim that young adults had a high mortality during the pandemic has been contested. Malnourishment, overcrowded medical camps and hospitals, and poor hygiene , exacerbated by the war, promoted bacterial superinfection , killing most of the victims after a typically prolonged death bed. The 1918 Spanish flu was the first of three flu pandemics caused by H1N1 influenza A virus ; the most recent one was the 2009 swine flu pandemic . The 1977 Russian flu was also caused by H1N1 virus. This pandemic was known by many different names—some old, some new—depending on place, time, and context. The etymology of alternative names historicises the scourge and its effects on people who would only learn years later that invisible viruses caused influenza . The lack of scientific answers led the Sierra Leone Weekly News ( Freetown ) to suggest a biblical framing in July 1918, using an interrogative from Exodus 16 in ancient Hebrew : [lower-alpha 1] "One thing is for certain—the doctors are at present flabbergasted; and we suggest that rather than calling the disease influenza they should for the present until they have it in hand, say Man hu —'What is it?'" Outbreaks of influenza-like illness were documented in 1916–17 at British military hospitals in Étaples , France , and just across the English Channel at Aldershot , England . Clinical indications in common with the 1918 pandemic included rapid symptom progression to a "dusky" heliotrope cyanosis of the face. This characteristic blue-violet cyanosis in expiring patients led to the name 'purple death'. The Aldershot physicians later wrote in The Lancet , "the influenza pneumococcal purulent bronchitis we and others described in 1916 and 1917 is fundamentally the same condition as the influenza of this present pandemic." This " purulent bronchitis " is not yet linked to the same A/H1N1 virus, but it may be a precursor. In 1918, ' epidemic influenza ' ( Italian : influenza , influence ), also known at the time as 'the grip' ( French : la grippe , grasp), appeared in Kansas in the U.S. during late spring, and early reports from Spain began appearing on 21 May. Reports from both places called it 'three-day fever' ( fiebre de los tres días ). Many alternative names are exonyms in the practice of making new infectious diseases seem foreign. This pattern was observed even before the 1889–1890 pandemic , also known as the 'Russian flu', when the Russians already called epidemic influenza the 'Chinese catarrh', the Germans called it the 'Russian pest', while the Italians in turn called it the 'German disease'. These epithets were re-used in the 1918 pandemic, along with new ones. Outside Spain, the disease was soon misnamed 'Spanish influenza'. In a 2 June 1918 The Times of London dispatch titled, "The Spanish Epidemic," a correspondent in Madrid reported over 100,000 victims of, "The unknown disease…clearly of a gripal character," without referring to "Spanish influenza" directly. Three weeks later The Times reported that, "Everybody thinks of it as the 'Spanish' influenza to-day." Three days after that an advertisement appeared in The Times for Formamint tablets to prevent "Spanish influenza". When it reached Moscow, Pravda announced, " Ispánka (the Spanish lady) is in town," making 'the Spanish lady' another common name. The outbreak did not originate in Spain (see below ), but reporting did, due to wartime censorship in belligerent nations. Spain was a neutral country unconcerned with appearances of combat readiness , and without a wartime propaganda machine to prop up morale ; so its newspapers freely reported epidemic effects, including King Alfonso XIII 's illness, making Spain the apparent locus of the epidemic. The censorship was so effective that Spain's health officials were unaware its neighboring countries were similarly affected. In an October 1918 "Madrid Letter" to the Journal of the American Medical Association , a Spanish official protested, "we were surprised to learn that the disease was making ravages in other countries, and that people there were calling it the 'Spanish grip'. And wherefore Spanish? …this epidemic was not born in Spain, and this should be recorded as a historic vindication." But before this letter could be published, The Serbian Newspaper ( Corfu ) said, "Various countries have been assigning the origin of this imposing guest to each other for quite some time, and at one point in time they agreed to assign its origin to the kind and neutral Spain…" French press initially used 'American flu', but adopted 'Spanish flu' in lieu of antagonizing an ally. In the spring of 1918, British soldiers called it 'Flanders flu', while German soldiers used ' Flandern-Fieber ' (Flemish fever), both after a famous battlefield in Belgium where many soldiers on both sides fell ill. In Senegal it was named 'Brazilian flu', and in Brazil , 'German flu'. In Spain it was also known as the 'French flu' ( gripe francesa ), or the 'Naples Soldier' ( Soldado de Nápoles ), after a popular song from a zarzuela . [lower-alpha 2] Spanish flu ( gripe española ) is now a common name in Spain, but remains controversial there. Other names derived from geopolitical borders and social boundaries. In Poland it was the ' Bolshevik disease', while the Bolsheviks referred to it as the ' Kirghiz disease'. Some Africans called it a 'white man's sickness', but in South Africa , white men also used the ethnophaulism 'kaffersiekte' (lit. negro disease). Japan blamed sumo wrestlers for bringing the disease home from a match in Taiwan by calling it 'sumo flu' ( Sumo Kaze ), even though three top wrestlers died there. World Health Organization 'best practices' first published in 2015 now aim to prevent social stigma by no longer associating culturally significant names with new diseases, listing "Spanish flu" under "examples to be avoided". Many authors now eschew calling this the Spanish flu, instead using variations of '1918–19/20 flu/influenza pandemic'. Some language endonyms did not name specific regions or groups of people. Examples specific to this pandemic include: Northern Ndebele : 'Malibuzwe' (let enquiries be made concerning it), Swahili : 'Ugonjo huo kichwa na kukohoa na kiuno' (the disease of head and coughing and spine), Yao : 'chipindupindu' (disease from seeking to make a profit in wartime), Otjiherero : 'kaapitohanga' (disease which passes through like a bullet), and Persian : 'nakhushi-yi bad' (disease of the wind). This outbreak was also commonly known as the 'great influenza epidemic', after the 'great war', a common name for World War I before World War II . French military doctors originally called it 'disease 11' ( maladie onze ). German doctors downplayed the severity by calling it 'pseudo influenza' ( Latin: pseudo , false), while in Africa, doctors tried to get patients to take it more seriously by calling it 'influenza vera' ( Latin: vera , true). A children's song from the 1889–90 flu pandemic was shortened and adapted into a skipping-rope rhyme popular in 1918. It is a metaphor for the transmissibility of 'Influenza', where that name was clipped to the apheresis 'Enza': I had a little bird, its name was Enza. I opened the window, and in-flu-enza.Outbreaks of influenza-like illness were documented in 1916–17 at British military hospitals in Étaples , France , and just across the English Channel at Aldershot , England . Clinical indications in common with the 1918 pandemic included rapid symptom progression to a "dusky" heliotrope cyanosis of the face. This characteristic blue-violet cyanosis in expiring patients led to the name 'purple death'. The Aldershot physicians later wrote in The Lancet , "the influenza pneumococcal purulent bronchitis we and others described in 1916 and 1917 is fundamentally the same condition as the influenza of this present pandemic." This " purulent bronchitis " is not yet linked to the same A/H1N1 virus, but it may be a precursor. In 1918, ' epidemic influenza ' ( Italian : influenza , influence ), also known at the time as 'the grip' ( French : la grippe , grasp), appeared in Kansas in the U.S. during late spring, and early reports from Spain began appearing on 21 May. Reports from both places called it 'three-day fever' ( fiebre de los tres días ). Many alternative names are exonyms in the practice of making new infectious diseases seem foreign. This pattern was observed even before the 1889–1890 pandemic , also known as the 'Russian flu', when the Russians already called epidemic influenza the 'Chinese catarrh', the Germans called it the 'Russian pest', while the Italians in turn called it the 'German disease'. These epithets were re-used in the 1918 pandemic, along with new ones. Outside Spain, the disease was soon misnamed 'Spanish influenza'. In a 2 June 1918 The Times of London dispatch titled, "The Spanish Epidemic," a correspondent in Madrid reported over 100,000 victims of, "The unknown disease…clearly of a gripal character," without referring to "Spanish influenza" directly. Three weeks later The Times reported that, "Everybody thinks of it as the 'Spanish' influenza to-day." Three days after that an advertisement appeared in The Times for Formamint tablets to prevent "Spanish influenza". When it reached Moscow, Pravda announced, " Ispánka (the Spanish lady) is in town," making 'the Spanish lady' another common name. The outbreak did not originate in Spain (see below ), but reporting did, due to wartime censorship in belligerent nations. Spain was a neutral country unconcerned with appearances of combat readiness , and without a wartime propaganda machine to prop up morale ; so its newspapers freely reported epidemic effects, including King Alfonso XIII 's illness, making Spain the apparent locus of the epidemic. The censorship was so effective that Spain's health officials were unaware its neighboring countries were similarly affected. In an October 1918 "Madrid Letter" to the Journal of the American Medical Association , a Spanish official protested, "we were surprised to learn that the disease was making ravages in other countries, and that people there were calling it the 'Spanish grip'. And wherefore Spanish? …this epidemic was not born in Spain, and this should be recorded as a historic vindication." But before this letter could be published, The Serbian Newspaper ( Corfu ) said, "Various countries have been assigning the origin of this imposing guest to each other for quite some time, and at one point in time they agreed to assign its origin to the kind and neutral Spain…" French press initially used 'American flu', but adopted 'Spanish flu' in lieu of antagonizing an ally. In the spring of 1918, British soldiers called it 'Flanders flu', while German soldiers used ' Flandern-Fieber ' (Flemish fever), both after a famous battlefield in Belgium where many soldiers on both sides fell ill. In Senegal it was named 'Brazilian flu', and in Brazil , 'German flu'. In Spain it was also known as the 'French flu' ( gripe francesa ), or the 'Naples Soldier' ( Soldado de Nápoles ), after a popular song from a zarzuela . [lower-alpha 2] Spanish flu ( gripe española ) is now a common name in Spain, but remains controversial there. Other names derived from geopolitical borders and social boundaries. In Poland it was the ' Bolshevik disease', while the Bolsheviks referred to it as the ' Kirghiz disease'. Some Africans called it a 'white man's sickness', but in South Africa , white men also used the ethnophaulism 'kaffersiekte' (lit. negro disease). Japan blamed sumo wrestlers for bringing the disease home from a match in Taiwan by calling it 'sumo flu' ( Sumo Kaze ), even though three top wrestlers died there. World Health Organization 'best practices' first published in 2015 now aim to prevent social stigma by no longer associating culturally significant names with new diseases, listing "Spanish flu" under "examples to be avoided". Many authors now eschew calling this the Spanish flu, instead using variations of '1918–19/20 flu/influenza pandemic'. Outside Spain, the disease was soon misnamed 'Spanish influenza'. In a 2 June 1918 The Times of London dispatch titled, "The Spanish Epidemic," a correspondent in Madrid reported over 100,000 victims of, "The unknown disease…clearly of a gripal character," without referring to "Spanish influenza" directly. Three weeks later The Times reported that, "Everybody thinks of it as the 'Spanish' influenza to-day." Three days after that an advertisement appeared in The Times for Formamint tablets to prevent "Spanish influenza". When it reached Moscow, Pravda announced, " Ispánka (the Spanish lady) is in town," making 'the Spanish lady' another common name. The outbreak did not originate in Spain (see below ), but reporting did, due to wartime censorship in belligerent nations. Spain was a neutral country unconcerned with appearances of combat readiness , and without a wartime propaganda machine to prop up morale ; so its newspapers freely reported epidemic effects, including King Alfonso XIII 's illness, making Spain the apparent locus of the epidemic. The censorship was so effective that Spain's health officials were unaware its neighboring countries were similarly affected. In an October 1918 "Madrid Letter" to the Journal of the American Medical Association , a Spanish official protested, "we were surprised to learn that the disease was making ravages in other countries, and that people there were calling it the 'Spanish grip'. And wherefore Spanish? …this epidemic was not born in Spain, and this should be recorded as a historic vindication." But before this letter could be published, The Serbian Newspaper ( Corfu ) said, "Various countries have been assigning the origin of this imposing guest to each other for quite some time, and at one point in time they agreed to assign its origin to the kind and neutral Spain…" French press initially used 'American flu', but adopted 'Spanish flu' in lieu of antagonizing an ally. In the spring of 1918, British soldiers called it 'Flanders flu', while German soldiers used ' Flandern-Fieber ' (Flemish fever), both after a famous battlefield in Belgium where many soldiers on both sides fell ill. In Senegal it was named 'Brazilian flu', and in Brazil , 'German flu'. In Spain it was also known as the 'French flu' ( gripe francesa ), or the 'Naples Soldier' ( Soldado de Nápoles ), after a popular song from a zarzuela . [lower-alpha 2] Spanish flu ( gripe española ) is now a common name in Spain, but remains controversial there. Other names derived from geopolitical borders and social boundaries. In Poland it was the ' Bolshevik disease', while the Bolsheviks referred to it as the ' Kirghiz disease'. Some Africans called it a 'white man's sickness', but in South Africa , white men also used the ethnophaulism 'kaffersiekte' (lit. negro disease). Japan blamed sumo wrestlers for bringing the disease home from a match in Taiwan by calling it 'sumo flu' ( Sumo Kaze ), even though three top wrestlers died there. World Health Organization 'best practices' first published in 2015 now aim to prevent social stigma by no longer associating culturally significant names with new diseases, listing "Spanish flu" under "examples to be avoided". Many authors now eschew calling this the Spanish flu, instead using variations of '1918–19/20 flu/influenza pandemic'. Some language endonyms did not name specific regions or groups of people. Examples specific to this pandemic include: Northern Ndebele : 'Malibuzwe' (let enquiries be made concerning it), Swahili : 'Ugonjo huo kichwa na kukohoa na kiuno' (the disease of head and coughing and spine), Yao : 'chipindupindu' (disease from seeking to make a profit in wartime), Otjiherero : 'kaapitohanga' (disease which passes through like a bullet), and Persian : 'nakhushi-yi bad' (disease of the wind). This outbreak was also commonly known as the 'great influenza epidemic', after the 'great war', a common name for World War I before World War II . French military doctors originally called it 'disease 11' ( maladie onze ). German doctors downplayed the severity by calling it 'pseudo influenza' ( Latin: pseudo , false), while in Africa, doctors tried to get patients to take it more seriously by calling it 'influenza vera' ( Latin: vera , true). A children's song from the 1889–90 flu pandemic was shortened and adapted into a skipping-rope rhyme popular in 1918. It is a metaphor for the transmissibility of 'Influenza', where that name was clipped to the apheresis 'Enza': I had a little bird, its name was Enza. I opened the window, and in-flu-enza.The pandemic is conventionally marked as having begun on 4 March 1918 with the recording of the case of Albert Gitchell, an army cook at Camp Funston in Kansas , United States, despite there having been cases before him. The disease had already been observed 200 miles (320 km) away in Haskell County as early as January 1918, prompting local doctor Loring Miner to warn the editors of the U.S. Public Health Service 's academic journal Public Health Reports . Within days of the 4 March first case at Camp Funston, 522 men at the camp had reported sick. By 11 March 1918, the virus had reached Queens , New York. Failure to take preventive measures in March/April was later criticized. As the U.S. had entered World War I, the disease quickly spread from Camp Funston, a major training ground for troops of the American Expeditionary Forces , to other U.S. Army camps and Europe, becoming an epidemic in the Midwest , East Coast , and French ports by April 1918, and reaching the Western Front by the middle of the month. It then quickly spread to the rest of France, Great Britain, Italy, and Spain and in May reached Wrocław and Odessa . After the signing of the Treaty of Brest-Litovsk (March 1918), Germany started releasing Russian prisoners of war, who then brought the disease to their country. It reached North Africa, India, and Japan in May, and soon after had likely gone around the world as there had been recorded cases in Southeast Asia in April. In June an outbreak was reported in China . After reaching Australia in July, the wave started to recede. The first wave of the flu lasted from the first quarter of 1918 and was relatively mild. Mortality rates were not appreciably above normal; in the United States ~75,000 flu-related deaths were reported in the first six months of 1918, compared to ~63,000 deaths during the same time period in 1915. In Madrid, Spain, fewer than 1,000 people died from influenza between May and June 1918. There were no reported quarantines during the first quarter of 1918. However, the first wave caused a significant disruption in the military operations of World War I , with three-quarters of French troops, half the British forces, and over 900,000 German soldiers sick. The second wave began in the second half of August 1918, probably spreading to Boston , Massachusetts and Freetown , Sierra Leone , by ships from Brest , where it had likely arrived with American troops or French recruits for naval training. From the Boston Navy Yard and Camp Devens (later renamed Fort Devens ), about 30 miles west of Boston, other U.S. military sites were soon afflicted, as were troops being transported to Europe. Helped by troop movements, it spread over the next two months to all of North America, and then to Central and South America , also reaching Brazil and the Caribbean on ships. In July 1918, the Ottoman Empire saw its first cases in some soldiers. From Freetown, the pandemic continued to spread through West Africa along the coast, rivers, and the colonial railways, and from railheads to more remote communities, while South Africa received it in September on ships bringing back members of the South African Native Labour Corps returning from France. From there it spread around southern Africa and beyond the Zambezi , reaching Ethiopia in November. On 15 September, New York City saw its first fatality from influenza. The Philadelphia Liberty Loans Parade , held in Philadelphia , Pennsylvania , on 28 September 1918 to promote government bonds for World War I, resulted in 12,000 deaths after a major outbreak of the illness spread among people who had attended the parade. From Europe, the second wave swept through Russia in a southwest–northeast diagonal front, as well as being brought to Arkhangelsk by the North Russia intervention , and then spread throughout Asia following the Russian Civil War and the Trans-Siberian railway , reaching Iran (where it spread through the holy city of Mashhad ), and then later India in September, as well as China and Japan in October. The celebrations of the Armistice of 11 November 1918 also caused outbreaks in Lima and Nairobi , but by December the wave was mostly over. The second wave of the 1918 pandemic was much more deadly than the first. The first wave had resembled typical flu epidemics; those most at risk were the sick and elderly, while younger, healthier people recovered easily. October 1918 was the month with the highest fatality rate of the whole pandemic. In the United States, ~292,000 deaths were reported between September–December 1918, compared to ~26,000 during the same time period in 1915. The Netherlands reported over 40,000 deaths from influenza and acute respiratory disease. Bombay reported ~15,000 deaths in a population of 1.1 million. The 1918 flu pandemic in India was especially deadly, with an estimated 12.5–20 million deaths in the last quarter of 1918 alone. [ page needed ] Pandemic activity persisted, in general, into 1919 in many places. This persistence in activity is possibly attributable to climate, specifically in the Northern Hemisphere , where it was winter and thus the usual time for influenza activity. The pandemic nonetheless continued into 1919 largely independent of region and climate. Cases began to rise again in some parts of the United States as early as late November 1918, with the Public Health Service issuing its first report of a "recrudescence of the disease" being felt in "widely scattered localities" in early December. This resurgent activity varied across the country, however, possibly on account of differing restrictions. Michigan , for example, experienced a swift resurgence of influenza that reached its peak in December, possibly as a result of the lifting of the ban on public gatherings. Pandemic interventions, such as bans on public gatherings and the closing of schools, were reimposed in many places in an attempt to suppress the spread. There was "a very sudden and very marked rise in general death rate" in most cities in January 1919; nearly all experienced "some degree of recrudescence" of the flu in January and February. : 153–154 Significant outbreaks occurred in cities including Los Angeles , New York City, Memphis , Nashville , San Francisco , and St. Louis . By 21 February, with some local variation, influenza activity was reported to have been declining since mid-January in all parts of the country. Following this "first great epidemic period" that had commenced in October 1918, deaths from pneumonia and influenza were "somewhat below average" in the large cities of the United States between May 1919 and January 1920. : 158 Nonetheless, nearly 160,000 deaths were attributed to these causes in the first six months of 1919. It was not until later in the winter and into the spring that a clearer resurgence appeared in Europe. A significant third wave had developed in England and Wales by mid-February, peaking in early March, though it did not fully subside until May. France also experienced a significant wave that peaked in February, alongside the Netherlands. Norway , Finland , and Switzerland saw recrudescences of pandemic activity in March, and Sweden in April. Much of Spain was affected by "a substantial recrudescent wave" of influenza between January and April 1919. Portugal experienced a resurgence in pandemic activity that lasted from March to September 1919, with the greatest impact being felt on the west coast and in the north of the country; all districts were affected between April and May specifically. Influenza entered Australia for the first time in January 1919 after a strict maritime quarantine had shielded the country through the latter part of 1918. It assumed epidemic proportions first in Melbourne , peaking in mid-February. The flu soon appeared in neighboring New South Wales and South Australia and then spread across the country throughout the year. New South Wales experienced its first wave of infection between mid-March and late May, while a second, more severe wave occurred in Victoria between April and June. Land quarantine measures hindered the spread of the disease, resulting in varied experiences of exposures and outbreaks among the various states. Queensland was not infected until late April; Western Australia avoided the disease until early June, and Tasmania remained free from it until mid-August. Out of the six states, Victoria and New South Wales experienced generally more extensive epidemics. Each experienced another significant wave of illness over the winter. The second epidemic in New South Wales was more severe than the first, while Victoria saw a third wave that was somewhat less extensive than its second, more akin to its first. The disease also reached other parts of the world for the first time in 1919, such as Madagascar , which saw its first cases in April; the outbreak had spread to practically all sections of the island by June. In other parts, influenza recurred in the form of a true "third wave". Hong Kong experienced another outbreak in June, as did South Africa during its fall and winter months in the Southern Hemisphere . New Zealand also experienced some cases in May. Parts of South America experienced a resurgence of pandemic activity throughout 1919. A third wave hit Brazil between January and June. Between July 1919 and February 1920, Chile , which had been affected for the first time just in October 1918, experienced a severe second wave, with mortality peaking in August 1919. Montevideo similarly experienced a second outbreak between July and September. The third wave particularly affected Spain, Serbia , Mexico and Great Britain, resulting in hundreds of thousands of deaths. It was in general less severe than the second wave but still much more deadly than the initial first wave. In the Northern Hemisphere, fears of a "recurrence" of the flu grew as fall approached. Experts cited the history of past flu epidemics, such as that of 1889–1890, to predict that such a recurrence a year later was not unlikely, though not all agreed. In September 1919, U.S. Surgeon General Rupert Blue said a return of the flu later in the year would "probably, but by no means certainly," occur. France had readied a public information campaign before the end of the summer, and Britain began preparations in the fall with the manufacture of vaccine. In Japan, the flu broke out again in December and spread rapidly throughout the country, a fact attributed at the time to the coming of cold weather. Pandemic-related measures were renewed to check the spread of the outbreak, and health authorities recommended the use of masks. The epidemic intensified in the latter part of December before swiftly peaking in January. Between October 1919 and 23 January 1920, 780,000 cases were reported across the country, with at least 20,000 deaths recorded by that date. This apparently reflected "a condition of severity three times greater than for the corresponding period of" 1918–1919, during Japan's first epidemic. Nonetheless, the disease was regarded as being milder than it had been the year before, albeit more infectious. Despite its rapid peak at the beginning of the year, the outbreak persisted throughout the winter, before subsiding in the spring. In the United States, there were "almost continuously isolated or solitary cases" of flu throughout the spring and summer months of 1919. An increase in scattered cases became apparent as early as September, but Chicago experienced one of the first major outbreaks of the flu beginning in the middle of January. The Public Health Service announced it would take steps to "localize the epidemic", but the disease was already causing a simultaneous outbreak in Kansas City and quickly spread outward from the center of the country in no clear direction. A few days after its first announcement, PHS issued another assuring that the disease was under the control of state health authorities and that an outbreak of epidemic proportions was not expected. It became apparent within days of the start of Chicago's explosive growth in cases that the flu was spreading in the city at an even faster rate than in winter 1919, though fewer were dying. Within a week, new cases in the city had surpassed its peak during the 1919 wave. Around the same time, New York City began to see its own sudden increase in cases, and other cities around the country were soon to follow. Certain pandemic restrictions, such as the closing of schools and theaters and the staggering of business hours to avoid congestion, were reimposed in cities like Chicago, Memphis, and New York City. As they had during the epidemic in fall 1918, schools in New York City remained open, while those in Memphis were shuttered as part of more general restrictions on public gatherings. The fourth wave in the United States subsided as swiftly as it had appeared, reaching a peak in early February. "An epidemic of considerable proportions marked the early months of 1920", the U.S. Mortality Statistics would later note; according to data at this time, the epidemic resulted in one third as many deaths as the 1918–1919 experience. New York City alone reported 6,374 deaths between December 1919 and April 1920, almost twice the number of the first wave in spring 1918. Other U.S. cities including Detroit, Milwaukee, Kansas City, Minneapolis, and St. Louis were hit particularly hard, with death rates higher than all of 1918. The Territory of Hawaii experienced its peak of the pandemic in early 1920, recording 1,489 deaths from flu-related causes, compared with 615 in 1918 and 796 in 1919. Poland experienced a devastating outbreak during the winter months, with its capital Warsaw reaching a peak of 158 deaths in a single week, compared to the peak of 92 reached in December 1918; however, the 1920 epidemic passed in a matter of weeks, while the 1918–1919 wave had developed over the entire second half of 1918. By contrast, the outbreak in western Europe was considered "benign", with the age distribution of deaths beginning to take on that of seasonal flu . Five countries in Europe (Spain, Denmark, Finland, Germany and Switzerland) recorded a late peak between January–April 1920. Mexico experienced a fourth wave between February and March. In South America, Peru experienced "asynchronous recrudescent waves" throughout the year. A severe third wave hit Lima , the capital city, between January and March, resulting in an all-cause excess mortality rate approximately four times greater than that of the 1918–1919 wave. Ica similarly experienced another severe pandemic wave in 1920, between July and October. A fourth wave also occurred in Brazil, in February. Korea and Taiwan , both colonies of Japan at this time, also experienced pronounced outbreaks in late 1919 and early 1920. By mid-1920, the pandemic was largely considered to be "over" by the public as well as governments. Though parts of Chile experienced a third, milder wave between November 1920 and March 1921, the flu seemed to be mostly absent through the winter of 1920–1921. : 167 In the United States, for example, deaths from pneumonia and influenza were "very much lower than for many years". : 167 Influenza began to be reported again from many places in 1921. : 168 The pandemic continued to be felt in Chile, where a fourth wave affected seven of its 24 provinces between June and December 1921. The winter of 1921–1922 was the first major reappearance of influenza in the Northern Hemisphere, in many parts its most significant occurrence since the main pandemic in late 1918. Northwestern Europe was particularly affected. All-cause mortality in the Netherlands approximately doubled in January 1922 alone. : 168 In Helsinki , a major epidemic (the fifth since 1918) prevailed between November and December 1921. The flu was also widespread in the United States, its prevalence in California reportedly greater in early March 1922 than at any point since 1920. : 172 In the years after 1920, the disease, a novel one in 1918, assumed a more familiar nature, coming to represent at least one form of the "seasonal flu". The virus, H1N1, remained endemic, occasionally causing more severe or otherwise notable outbreaks as it gradually evolved over the years. The period since its initial appearance in 1918 has been termed a "pandemic era", in which all flu pandemics since its emergence have been caused by its own descendants. Following the first of these post-1918 pandemics , in 1957, the virus was totally displaced by the novel H2N2 , the reassortant product of the human H1N1 and an avian influenza virus, which thereafter became the active influenza A virus in humans. In 1977, an influenza virus bearing a very close resemblance to the seasonal H1N1, which had not been seen since the 1950s, appeared in Russia and subsequently initiated a "technical" pandemic that principally affected those 26 years of age and younger. While some natural explanations, such as the virus remaining in some frozen state for 20 years, have been proposed to explain this unprecedented phenomenon, the nature of influenza itself has been cited in favor of human involvement of some kind, such as an accidental leak from a lab where the old virus had been preserved for research purposes. Following this miniature pandemic, the reemerged H1N1 became endemic once again but did not displace the other active influenza A virus, H3N2 (which itself had displaced H2N2 through a pandemic in 1968 ). For the first time, two influenza A viruses were observed in cocirculation. This state of affairs has persisted even after 2009, when a novel H1N1 virus emerged, sparked a pandemic , and thereafter took the place of the seasonal H1N1 to circulate alongside H3N2. Despite its name, historical and epidemiological data cannot identify the geographic origin of the Spanish flu. However, several theories have been proposed. The first confirmed cases originated in the United States. Historian Alfred W. Crosby stated in 2003 that the flu originated in Kansas , and author John M. Barry described a January 1918 outbreak in Haskell County, Kansas , as the point of origin in his 2004 article. A 2018 study of tissue slides and medical reports led by evolutionary biology professor Michael Worobey found evidence against the disease originating from Kansas, as those cases were milder and had fewer deaths compared to the infections in New York City in the same period. The study did find evidence through phylogenetic analyses that the virus likely had a North American origin, though it was not conclusive. In addition, the haemagglutinin glycoproteins of the virus suggest that it originated long before 1918, and other studies suggest that the reassortment of the H1N1 virus likely occurred in or around 1915. The major U.K. troop staging and hospital camp in Étaples in France has been theorized by virologist John Oxford as being at the center of the Spanish flu. His study found that in late 1916 the Étaples camp was hit by the onset of a new disease with high mortality that caused symptoms similar to the flu. According to Oxford, a similar outbreak occurred in March 1917 at army barracks in Aldershot , and military pathologists later recognized these early outbreaks as the same disease as the Spanish flu. The overcrowded camp and hospital at Étaples was an ideal environment for the spread of a respiratory virus. The hospital treated thousands of victims of poison gas attacks, and other casualties of war, and 100,000 soldiers passed through the camp every day. It also was home to a piggery and poultry was regularly brought in from surrounding villages to feed the camp. Oxford and his team postulated that a precursor virus, harbored in birds, mutated and then migrated to pigs kept near the front. A report published in 2016 in the Journal of the Chinese Medical Association found evidence that the 1918 virus had been circulating in the European armies for months and possibly years before the 1918 pandemic. Political scientist Andrew Price-Smith published data from the Austrian archives suggesting the influenza began in Austria in early 1917. A 2009 study in Influenza and Other Respiratory Viruses found that Spanish flu mortality simultaneously peaked within the two-month period of October and November 1918 in all fourteen European countries analyzed, which is inconsistent with the pattern that researchers would expect if the virus had originated somewhere in Europe and then spread outwards. In 1993, Claude Hannoun, the leading expert on the Spanish flu at the Pasteur Institute , asserted the precursor virus was likely to have come from China and then mutated in the United States near Boston and from there spread to Brest , France, Europe's battlefields, the rest of Europe, and the rest of the world, with Allied soldiers and sailors as the main disseminators. Hannoun considered several alternative hypotheses of origin, such as Spain, Kansas, and Brest, as being possible, but not likely. In 2014, historian Mark Humphries argued that the mobilization of 96,000 Chinese laborers to work behind the British and French lines might have been the source of the pandemic. Humphries, of the Memorial University of Newfoundland in St. John's , based his conclusions on newly unearthed records. He found archival evidence that a respiratory illness that struck northern China (where the laborers came from) in November 1917 was identified a year later by Chinese health officials as identical to the Spanish flu. Unfortunately, no tissue samples have survived for modern comparison. Nevertheless, there were some reports of respiratory illness on parts of the path the laborers took to get to Europe, which also passed through North America. China was one of the few regions of the world seemingly less affected by the Spanish flu pandemic, where several studies have documented a comparatively mild flu season in 1918. (Although this is disputed due to lack of data during the Warlord Period , see Around the globe .) This has led to speculation that the Spanish flu pandemic originated in China, as the lower rates of flu mortality may be explained by the Chinese population's previously acquired immunity to the flu virus. In the Guangdong Province it was reported that early outbreaks of influenza in 1918 disproportionately impacted young men. The June outbreak infected children and adolescents between 11 and 20 years of age, while the October outbreak was most common in those aged 11 to 15. A report published in 2016 in the Journal of the Chinese Medical Association found no evidence that the 1918 virus was imported to Europe via Chinese and Southeast Asian soldiers and workers and instead found evidence of its circulation in Europe before the pandemic. The 2016 study found that the low flu mortality rate (an estimated one in a thousand) recorded among the Chinese and Southeast Asian workers in Europe suggests that the Asian units were not different from other Allied military units in France at the end of 1918 and, thus, were not a likely source of a new lethal virus. Further evidence against the disease being spread by Chinese workers was that workers entered Europe through other routes that did not result in a detectable spread, making them unlikely to have been the original hosts. The pandemic is conventionally marked as having begun on 4 March 1918 with the recording of the case of Albert Gitchell, an army cook at Camp Funston in Kansas , United States, despite there having been cases before him. The disease had already been observed 200 miles (320 km) away in Haskell County as early as January 1918, prompting local doctor Loring Miner to warn the editors of the U.S. Public Health Service 's academic journal Public Health Reports . Within days of the 4 March first case at Camp Funston, 522 men at the camp had reported sick. By 11 March 1918, the virus had reached Queens , New York. Failure to take preventive measures in March/April was later criticized. As the U.S. had entered World War I, the disease quickly spread from Camp Funston, a major training ground for troops of the American Expeditionary Forces , to other U.S. Army camps and Europe, becoming an epidemic in the Midwest , East Coast , and French ports by April 1918, and reaching the Western Front by the middle of the month. It then quickly spread to the rest of France, Great Britain, Italy, and Spain and in May reached Wrocław and Odessa . After the signing of the Treaty of Brest-Litovsk (March 1918), Germany started releasing Russian prisoners of war, who then brought the disease to their country. It reached North Africa, India, and Japan in May, and soon after had likely gone around the world as there had been recorded cases in Southeast Asia in April. In June an outbreak was reported in China . After reaching Australia in July, the wave started to recede. The first wave of the flu lasted from the first quarter of 1918 and was relatively mild. Mortality rates were not appreciably above normal; in the United States ~75,000 flu-related deaths were reported in the first six months of 1918, compared to ~63,000 deaths during the same time period in 1915. In Madrid, Spain, fewer than 1,000 people died from influenza between May and June 1918. There were no reported quarantines during the first quarter of 1918. However, the first wave caused a significant disruption in the military operations of World War I , with three-quarters of French troops, half the British forces, and over 900,000 German soldiers sick. The second wave began in the second half of August 1918, probably spreading to Boston , Massachusetts and Freetown , Sierra Leone , by ships from Brest , where it had likely arrived with American troops or French recruits for naval training. From the Boston Navy Yard and Camp Devens (later renamed Fort Devens ), about 30 miles west of Boston, other U.S. military sites were soon afflicted, as were troops being transported to Europe. Helped by troop movements, it spread over the next two months to all of North America, and then to Central and South America , also reaching Brazil and the Caribbean on ships. In July 1918, the Ottoman Empire saw its first cases in some soldiers. From Freetown, the pandemic continued to spread through West Africa along the coast, rivers, and the colonial railways, and from railheads to more remote communities, while South Africa received it in September on ships bringing back members of the South African Native Labour Corps returning from France. From there it spread around southern Africa and beyond the Zambezi , reaching Ethiopia in November. On 15 September, New York City saw its first fatality from influenza. The Philadelphia Liberty Loans Parade , held in Philadelphia , Pennsylvania , on 28 September 1918 to promote government bonds for World War I, resulted in 12,000 deaths after a major outbreak of the illness spread among people who had attended the parade. From Europe, the second wave swept through Russia in a southwest–northeast diagonal front, as well as being brought to Arkhangelsk by the North Russia intervention , and then spread throughout Asia following the Russian Civil War and the Trans-Siberian railway , reaching Iran (where it spread through the holy city of Mashhad ), and then later India in September, as well as China and Japan in October. The celebrations of the Armistice of 11 November 1918 also caused outbreaks in Lima and Nairobi , but by December the wave was mostly over. The second wave of the 1918 pandemic was much more deadly than the first. The first wave had resembled typical flu epidemics; those most at risk were the sick and elderly, while younger, healthier people recovered easily. October 1918 was the month with the highest fatality rate of the whole pandemic. In the United States, ~292,000 deaths were reported between September–December 1918, compared to ~26,000 during the same time period in 1915. The Netherlands reported over 40,000 deaths from influenza and acute respiratory disease. Bombay reported ~15,000 deaths in a population of 1.1 million. The 1918 flu pandemic in India was especially deadly, with an estimated 12.5–20 million deaths in the last quarter of 1918 alone. [ page needed ] Pandemic activity persisted, in general, into 1919 in many places. This persistence in activity is possibly attributable to climate, specifically in the Northern Hemisphere , where it was winter and thus the usual time for influenza activity. The pandemic nonetheless continued into 1919 largely independent of region and climate. Cases began to rise again in some parts of the United States as early as late November 1918, with the Public Health Service issuing its first report of a "recrudescence of the disease" being felt in "widely scattered localities" in early December. This resurgent activity varied across the country, however, possibly on account of differing restrictions. Michigan , for example, experienced a swift resurgence of influenza that reached its peak in December, possibly as a result of the lifting of the ban on public gatherings. Pandemic interventions, such as bans on public gatherings and the closing of schools, were reimposed in many places in an attempt to suppress the spread. There was "a very sudden and very marked rise in general death rate" in most cities in January 1919; nearly all experienced "some degree of recrudescence" of the flu in January and February. : 153–154 Significant outbreaks occurred in cities including Los Angeles , New York City, Memphis , Nashville , San Francisco , and St. Louis . By 21 February, with some local variation, influenza activity was reported to have been declining since mid-January in all parts of the country. Following this "first great epidemic period" that had commenced in October 1918, deaths from pneumonia and influenza were "somewhat below average" in the large cities of the United States between May 1919 and January 1920. : 158 Nonetheless, nearly 160,000 deaths were attributed to these causes in the first six months of 1919. It was not until later in the winter and into the spring that a clearer resurgence appeared in Europe. A significant third wave had developed in England and Wales by mid-February, peaking in early March, though it did not fully subside until May. France also experienced a significant wave that peaked in February, alongside the Netherlands. Norway , Finland , and Switzerland saw recrudescences of pandemic activity in March, and Sweden in April. Much of Spain was affected by "a substantial recrudescent wave" of influenza between January and April 1919. Portugal experienced a resurgence in pandemic activity that lasted from March to September 1919, with the greatest impact being felt on the west coast and in the north of the country; all districts were affected between April and May specifically. Influenza entered Australia for the first time in January 1919 after a strict maritime quarantine had shielded the country through the latter part of 1918. It assumed epidemic proportions first in Melbourne , peaking in mid-February. The flu soon appeared in neighboring New South Wales and South Australia and then spread across the country throughout the year. New South Wales experienced its first wave of infection between mid-March and late May, while a second, more severe wave occurred in Victoria between April and June. Land quarantine measures hindered the spread of the disease, resulting in varied experiences of exposures and outbreaks among the various states. Queensland was not infected until late April; Western Australia avoided the disease until early June, and Tasmania remained free from it until mid-August. Out of the six states, Victoria and New South Wales experienced generally more extensive epidemics. Each experienced another significant wave of illness over the winter. The second epidemic in New South Wales was more severe than the first, while Victoria saw a third wave that was somewhat less extensive than its second, more akin to its first. The disease also reached other parts of the world for the first time in 1919, such as Madagascar , which saw its first cases in April; the outbreak had spread to practically all sections of the island by June. In other parts, influenza recurred in the form of a true "third wave". Hong Kong experienced another outbreak in June, as did South Africa during its fall and winter months in the Southern Hemisphere . New Zealand also experienced some cases in May. Parts of South America experienced a resurgence of pandemic activity throughout 1919. A third wave hit Brazil between January and June. Between July 1919 and February 1920, Chile , which had been affected for the first time just in October 1918, experienced a severe second wave, with mortality peaking in August 1919. Montevideo similarly experienced a second outbreak between July and September. The third wave particularly affected Spain, Serbia , Mexico and Great Britain, resulting in hundreds of thousands of deaths. It was in general less severe than the second wave but still much more deadly than the initial first wave. In the Northern Hemisphere, fears of a "recurrence" of the flu grew as fall approached. Experts cited the history of past flu epidemics, such as that of 1889–1890, to predict that such a recurrence a year later was not unlikely, though not all agreed. In September 1919, U.S. Surgeon General Rupert Blue said a return of the flu later in the year would "probably, but by no means certainly," occur. France had readied a public information campaign before the end of the summer, and Britain began preparations in the fall with the manufacture of vaccine. In Japan, the flu broke out again in December and spread rapidly throughout the country, a fact attributed at the time to the coming of cold weather. Pandemic-related measures were renewed to check the spread of the outbreak, and health authorities recommended the use of masks. The epidemic intensified in the latter part of December before swiftly peaking in January. Between October 1919 and 23 January 1920, 780,000 cases were reported across the country, with at least 20,000 deaths recorded by that date. This apparently reflected "a condition of severity three times greater than for the corresponding period of" 1918–1919, during Japan's first epidemic. Nonetheless, the disease was regarded as being milder than it had been the year before, albeit more infectious. Despite its rapid peak at the beginning of the year, the outbreak persisted throughout the winter, before subsiding in the spring. In the United States, there were "almost continuously isolated or solitary cases" of flu throughout the spring and summer months of 1919. An increase in scattered cases became apparent as early as September, but Chicago experienced one of the first major outbreaks of the flu beginning in the middle of January. The Public Health Service announced it would take steps to "localize the epidemic", but the disease was already causing a simultaneous outbreak in Kansas City and quickly spread outward from the center of the country in no clear direction. A few days after its first announcement, PHS issued another assuring that the disease was under the control of state health authorities and that an outbreak of epidemic proportions was not expected. It became apparent within days of the start of Chicago's explosive growth in cases that the flu was spreading in the city at an even faster rate than in winter 1919, though fewer were dying. Within a week, new cases in the city had surpassed its peak during the 1919 wave. Around the same time, New York City began to see its own sudden increase in cases, and other cities around the country were soon to follow. Certain pandemic restrictions, such as the closing of schools and theaters and the staggering of business hours to avoid congestion, were reimposed in cities like Chicago, Memphis, and New York City. As they had during the epidemic in fall 1918, schools in New York City remained open, while those in Memphis were shuttered as part of more general restrictions on public gatherings. The fourth wave in the United States subsided as swiftly as it had appeared, reaching a peak in early February. "An epidemic of considerable proportions marked the early months of 1920", the U.S. Mortality Statistics would later note; according to data at this time, the epidemic resulted in one third as many deaths as the 1918–1919 experience. New York City alone reported 6,374 deaths between December 1919 and April 1920, almost twice the number of the first wave in spring 1918. Other U.S. cities including Detroit, Milwaukee, Kansas City, Minneapolis, and St. Louis were hit particularly hard, with death rates higher than all of 1918. The Territory of Hawaii experienced its peak of the pandemic in early 1920, recording 1,489 deaths from flu-related causes, compared with 615 in 1918 and 796 in 1919. Poland experienced a devastating outbreak during the winter months, with its capital Warsaw reaching a peak of 158 deaths in a single week, compared to the peak of 92 reached in December 1918; however, the 1920 epidemic passed in a matter of weeks, while the 1918–1919 wave had developed over the entire second half of 1918. By contrast, the outbreak in western Europe was considered "benign", with the age distribution of deaths beginning to take on that of seasonal flu . Five countries in Europe (Spain, Denmark, Finland, Germany and Switzerland) recorded a late peak between January–April 1920. Mexico experienced a fourth wave between February and March. In South America, Peru experienced "asynchronous recrudescent waves" throughout the year. A severe third wave hit Lima , the capital city, between January and March, resulting in an all-cause excess mortality rate approximately four times greater than that of the 1918–1919 wave. Ica similarly experienced another severe pandemic wave in 1920, between July and October. A fourth wave also occurred in Brazil, in February. Korea and Taiwan , both colonies of Japan at this time, also experienced pronounced outbreaks in late 1919 and early 1920. By mid-1920, the pandemic was largely considered to be "over" by the public as well as governments. Though parts of Chile experienced a third, milder wave between November 1920 and March 1921, the flu seemed to be mostly absent through the winter of 1920–1921. : 167 In the United States, for example, deaths from pneumonia and influenza were "very much lower than for many years". : 167 Influenza began to be reported again from many places in 1921. : 168 The pandemic continued to be felt in Chile, where a fourth wave affected seven of its 24 provinces between June and December 1921. The winter of 1921–1922 was the first major reappearance of influenza in the Northern Hemisphere, in many parts its most significant occurrence since the main pandemic in late 1918. Northwestern Europe was particularly affected. All-cause mortality in the Netherlands approximately doubled in January 1922 alone. : 168 In Helsinki , a major epidemic (the fifth since 1918) prevailed between November and December 1921. The flu was also widespread in the United States, its prevalence in California reportedly greater in early March 1922 than at any point since 1920. : 172 In the years after 1920, the disease, a novel one in 1918, assumed a more familiar nature, coming to represent at least one form of the "seasonal flu". The virus, H1N1, remained endemic, occasionally causing more severe or otherwise notable outbreaks as it gradually evolved over the years. The period since its initial appearance in 1918 has been termed a "pandemic era", in which all flu pandemics since its emergence have been caused by its own descendants. Following the first of these post-1918 pandemics , in 1957, the virus was totally displaced by the novel H2N2 , the reassortant product of the human H1N1 and an avian influenza virus, which thereafter became the active influenza A virus in humans. In 1977, an influenza virus bearing a very close resemblance to the seasonal H1N1, which had not been seen since the 1950s, appeared in Russia and subsequently initiated a "technical" pandemic that principally affected those 26 years of age and younger. While some natural explanations, such as the virus remaining in some frozen state for 20 years, have been proposed to explain this unprecedented phenomenon, the nature of influenza itself has been cited in favor of human involvement of some kind, such as an accidental leak from a lab where the old virus had been preserved for research purposes. Following this miniature pandemic, the reemerged H1N1 became endemic once again but did not displace the other active influenza A virus, H3N2 (which itself had displaced H2N2 through a pandemic in 1968 ). For the first time, two influenza A viruses were observed in cocirculation. This state of affairs has persisted even after 2009, when a novel H1N1 virus emerged, sparked a pandemic , and thereafter took the place of the seasonal H1N1 to circulate alongside H3N2. The pandemic is conventionally marked as having begun on 4 March 1918 with the recording of the case of Albert Gitchell, an army cook at Camp Funston in Kansas , United States, despite there having been cases before him. The disease had already been observed 200 miles (320 km) away in Haskell County as early as January 1918, prompting local doctor Loring Miner to warn the editors of the U.S. Public Health Service 's academic journal Public Health Reports . Within days of the 4 March first case at Camp Funston, 522 men at the camp had reported sick. By 11 March 1918, the virus had reached Queens , New York. Failure to take preventive measures in March/April was later criticized. As the U.S. had entered World War I, the disease quickly spread from Camp Funston, a major training ground for troops of the American Expeditionary Forces , to other U.S. Army camps and Europe, becoming an epidemic in the Midwest , East Coast , and French ports by April 1918, and reaching the Western Front by the middle of the month. It then quickly spread to the rest of France, Great Britain, Italy, and Spain and in May reached Wrocław and Odessa . After the signing of the Treaty of Brest-Litovsk (March 1918), Germany started releasing Russian prisoners of war, who then brought the disease to their country. It reached North Africa, India, and Japan in May, and soon after had likely gone around the world as there had been recorded cases in Southeast Asia in April. In June an outbreak was reported in China . After reaching Australia in July, the wave started to recede. The first wave of the flu lasted from the first quarter of 1918 and was relatively mild. Mortality rates were not appreciably above normal; in the United States ~75,000 flu-related deaths were reported in the first six months of 1918, compared to ~63,000 deaths during the same time period in 1915. In Madrid, Spain, fewer than 1,000 people died from influenza between May and June 1918. There were no reported quarantines during the first quarter of 1918. However, the first wave caused a significant disruption in the military operations of World War I , with three-quarters of French troops, half the British forces, and over 900,000 German soldiers sick. The second wave began in the second half of August 1918, probably spreading to Boston , Massachusetts and Freetown , Sierra Leone , by ships from Brest , where it had likely arrived with American troops or French recruits for naval training. From the Boston Navy Yard and Camp Devens (later renamed Fort Devens ), about 30 miles west of Boston, other U.S. military sites were soon afflicted, as were troops being transported to Europe. Helped by troop movements, it spread over the next two months to all of North America, and then to Central and South America , also reaching Brazil and the Caribbean on ships. In July 1918, the Ottoman Empire saw its first cases in some soldiers. From Freetown, the pandemic continued to spread through West Africa along the coast, rivers, and the colonial railways, and from railheads to more remote communities, while South Africa received it in September on ships bringing back members of the South African Native Labour Corps returning from France. From there it spread around southern Africa and beyond the Zambezi , reaching Ethiopia in November. On 15 September, New York City saw its first fatality from influenza. The Philadelphia Liberty Loans Parade , held in Philadelphia , Pennsylvania , on 28 September 1918 to promote government bonds for World War I, resulted in 12,000 deaths after a major outbreak of the illness spread among people who had attended the parade. From Europe, the second wave swept through Russia in a southwest–northeast diagonal front, as well as being brought to Arkhangelsk by the North Russia intervention , and then spread throughout Asia following the Russian Civil War and the Trans-Siberian railway , reaching Iran (where it spread through the holy city of Mashhad ), and then later India in September, as well as China and Japan in October. The celebrations of the Armistice of 11 November 1918 also caused outbreaks in Lima and Nairobi , but by December the wave was mostly over. The second wave of the 1918 pandemic was much more deadly than the first. The first wave had resembled typical flu epidemics; those most at risk were the sick and elderly, while younger, healthier people recovered easily. October 1918 was the month with the highest fatality rate of the whole pandemic. In the United States, ~292,000 deaths were reported between September–December 1918, compared to ~26,000 during the same time period in 1915. The Netherlands reported over 40,000 deaths from influenza and acute respiratory disease. Bombay reported ~15,000 deaths in a population of 1.1 million. The 1918 flu pandemic in India was especially deadly, with an estimated 12.5–20 million deaths in the last quarter of 1918 alone. [ page needed ]Pandemic activity persisted, in general, into 1919 in many places. This persistence in activity is possibly attributable to climate, specifically in the Northern Hemisphere , where it was winter and thus the usual time for influenza activity. The pandemic nonetheless continued into 1919 largely independent of region and climate. Cases began to rise again in some parts of the United States as early as late November 1918, with the Public Health Service issuing its first report of a "recrudescence of the disease" being felt in "widely scattered localities" in early December. This resurgent activity varied across the country, however, possibly on account of differing restrictions. Michigan , for example, experienced a swift resurgence of influenza that reached its peak in December, possibly as a result of the lifting of the ban on public gatherings. Pandemic interventions, such as bans on public gatherings and the closing of schools, were reimposed in many places in an attempt to suppress the spread. There was "a very sudden and very marked rise in general death rate" in most cities in January 1919; nearly all experienced "some degree of recrudescence" of the flu in January and February. : 153–154 Significant outbreaks occurred in cities including Los Angeles , New York City, Memphis , Nashville , San Francisco , and St. Louis . By 21 February, with some local variation, influenza activity was reported to have been declining since mid-January in all parts of the country. Following this "first great epidemic period" that had commenced in October 1918, deaths from pneumonia and influenza were "somewhat below average" in the large cities of the United States between May 1919 and January 1920. : 158 Nonetheless, nearly 160,000 deaths were attributed to these causes in the first six months of 1919. It was not until later in the winter and into the spring that a clearer resurgence appeared in Europe. A significant third wave had developed in England and Wales by mid-February, peaking in early March, though it did not fully subside until May. France also experienced a significant wave that peaked in February, alongside the Netherlands. Norway , Finland , and Switzerland saw recrudescences of pandemic activity in March, and Sweden in April. Much of Spain was affected by "a substantial recrudescent wave" of influenza between January and April 1919. Portugal experienced a resurgence in pandemic activity that lasted from March to September 1919, with the greatest impact being felt on the west coast and in the north of the country; all districts were affected between April and May specifically. Influenza entered Australia for the first time in January 1919 after a strict maritime quarantine had shielded the country through the latter part of 1918. It assumed epidemic proportions first in Melbourne , peaking in mid-February. The flu soon appeared in neighboring New South Wales and South Australia and then spread across the country throughout the year. New South Wales experienced its first wave of infection between mid-March and late May, while a second, more severe wave occurred in Victoria between April and June. Land quarantine measures hindered the spread of the disease, resulting in varied experiences of exposures and outbreaks among the various states. Queensland was not infected until late April; Western Australia avoided the disease until early June, and Tasmania remained free from it until mid-August. Out of the six states, Victoria and New South Wales experienced generally more extensive epidemics. Each experienced another significant wave of illness over the winter. The second epidemic in New South Wales was more severe than the first, while Victoria saw a third wave that was somewhat less extensive than its second, more akin to its first. The disease also reached other parts of the world for the first time in 1919, such as Madagascar , which saw its first cases in April; the outbreak had spread to practically all sections of the island by June. In other parts, influenza recurred in the form of a true "third wave". Hong Kong experienced another outbreak in June, as did South Africa during its fall and winter months in the Southern Hemisphere . New Zealand also experienced some cases in May. Parts of South America experienced a resurgence of pandemic activity throughout 1919. A third wave hit Brazil between January and June. Between July 1919 and February 1920, Chile , which had been affected for the first time just in October 1918, experienced a severe second wave, with mortality peaking in August 1919. Montevideo similarly experienced a second outbreak between July and September. The third wave particularly affected Spain, Serbia , Mexico and Great Britain, resulting in hundreds of thousands of deaths. It was in general less severe than the second wave but still much more deadly than the initial first wave.In the Northern Hemisphere, fears of a "recurrence" of the flu grew as fall approached. Experts cited the history of past flu epidemics, such as that of 1889–1890, to predict that such a recurrence a year later was not unlikely, though not all agreed. In September 1919, U.S. Surgeon General Rupert Blue said a return of the flu later in the year would "probably, but by no means certainly," occur. France had readied a public information campaign before the end of the summer, and Britain began preparations in the fall with the manufacture of vaccine. In Japan, the flu broke out again in December and spread rapidly throughout the country, a fact attributed at the time to the coming of cold weather. Pandemic-related measures were renewed to check the spread of the outbreak, and health authorities recommended the use of masks. The epidemic intensified in the latter part of December before swiftly peaking in January. Between October 1919 and 23 January 1920, 780,000 cases were reported across the country, with at least 20,000 deaths recorded by that date. This apparently reflected "a condition of severity three times greater than for the corresponding period of" 1918–1919, during Japan's first epidemic. Nonetheless, the disease was regarded as being milder than it had been the year before, albeit more infectious. Despite its rapid peak at the beginning of the year, the outbreak persisted throughout the winter, before subsiding in the spring. In the United States, there were "almost continuously isolated or solitary cases" of flu throughout the spring and summer months of 1919. An increase in scattered cases became apparent as early as September, but Chicago experienced one of the first major outbreaks of the flu beginning in the middle of January. The Public Health Service announced it would take steps to "localize the epidemic", but the disease was already causing a simultaneous outbreak in Kansas City and quickly spread outward from the center of the country in no clear direction. A few days after its first announcement, PHS issued another assuring that the disease was under the control of state health authorities and that an outbreak of epidemic proportions was not expected. It became apparent within days of the start of Chicago's explosive growth in cases that the flu was spreading in the city at an even faster rate than in winter 1919, though fewer were dying. Within a week, new cases in the city had surpassed its peak during the 1919 wave. Around the same time, New York City began to see its own sudden increase in cases, and other cities around the country were soon to follow. Certain pandemic restrictions, such as the closing of schools and theaters and the staggering of business hours to avoid congestion, were reimposed in cities like Chicago, Memphis, and New York City. As they had during the epidemic in fall 1918, schools in New York City remained open, while those in Memphis were shuttered as part of more general restrictions on public gatherings. The fourth wave in the United States subsided as swiftly as it had appeared, reaching a peak in early February. "An epidemic of considerable proportions marked the early months of 1920", the U.S. Mortality Statistics would later note; according to data at this time, the epidemic resulted in one third as many deaths as the 1918–1919 experience. New York City alone reported 6,374 deaths between December 1919 and April 1920, almost twice the number of the first wave in spring 1918. Other U.S. cities including Detroit, Milwaukee, Kansas City, Minneapolis, and St. Louis were hit particularly hard, with death rates higher than all of 1918. The Territory of Hawaii experienced its peak of the pandemic in early 1920, recording 1,489 deaths from flu-related causes, compared with 615 in 1918 and 796 in 1919. Poland experienced a devastating outbreak during the winter months, with its capital Warsaw reaching a peak of 158 deaths in a single week, compared to the peak of 92 reached in December 1918; however, the 1920 epidemic passed in a matter of weeks, while the 1918–1919 wave had developed over the entire second half of 1918. By contrast, the outbreak in western Europe was considered "benign", with the age distribution of deaths beginning to take on that of seasonal flu . Five countries in Europe (Spain, Denmark, Finland, Germany and Switzerland) recorded a late peak between January–April 1920. Mexico experienced a fourth wave between February and March. In South America, Peru experienced "asynchronous recrudescent waves" throughout the year. A severe third wave hit Lima , the capital city, between January and March, resulting in an all-cause excess mortality rate approximately four times greater than that of the 1918–1919 wave. Ica similarly experienced another severe pandemic wave in 1920, between July and October. A fourth wave also occurred in Brazil, in February. Korea and Taiwan , both colonies of Japan at this time, also experienced pronounced outbreaks in late 1919 and early 1920. By mid-1920, the pandemic was largely considered to be "over" by the public as well as governments. Though parts of Chile experienced a third, milder wave between November 1920 and March 1921, the flu seemed to be mostly absent through the winter of 1920–1921. : 167 In the United States, for example, deaths from pneumonia and influenza were "very much lower than for many years". : 167 Influenza began to be reported again from many places in 1921. : 168 The pandemic continued to be felt in Chile, where a fourth wave affected seven of its 24 provinces between June and December 1921. The winter of 1921–1922 was the first major reappearance of influenza in the Northern Hemisphere, in many parts its most significant occurrence since the main pandemic in late 1918. Northwestern Europe was particularly affected. All-cause mortality in the Netherlands approximately doubled in January 1922 alone. : 168 In Helsinki , a major epidemic (the fifth since 1918) prevailed between November and December 1921. The flu was also widespread in the United States, its prevalence in California reportedly greater in early March 1922 than at any point since 1920. : 172 In the years after 1920, the disease, a novel one in 1918, assumed a more familiar nature, coming to represent at least one form of the "seasonal flu". The virus, H1N1, remained endemic, occasionally causing more severe or otherwise notable outbreaks as it gradually evolved over the years. The period since its initial appearance in 1918 has been termed a "pandemic era", in which all flu pandemics since its emergence have been caused by its own descendants. Following the first of these post-1918 pandemics , in 1957, the virus was totally displaced by the novel H2N2 , the reassortant product of the human H1N1 and an avian influenza virus, which thereafter became the active influenza A virus in humans. In 1977, an influenza virus bearing a very close resemblance to the seasonal H1N1, which had not been seen since the 1950s, appeared in Russia and subsequently initiated a "technical" pandemic that principally affected those 26 years of age and younger. While some natural explanations, such as the virus remaining in some frozen state for 20 years, have been proposed to explain this unprecedented phenomenon, the nature of influenza itself has been cited in favor of human involvement of some kind, such as an accidental leak from a lab where the old virus had been preserved for research purposes. Following this miniature pandemic, the reemerged H1N1 became endemic once again but did not displace the other active influenza A virus, H3N2 (which itself had displaced H2N2 through a pandemic in 1968 ). For the first time, two influenza A viruses were observed in cocirculation. This state of affairs has persisted even after 2009, when a novel H1N1 virus emerged, sparked a pandemic , and thereafter took the place of the seasonal H1N1 to circulate alongside H3N2. Despite its name, historical and epidemiological data cannot identify the geographic origin of the Spanish flu. However, several theories have been proposed. The first confirmed cases originated in the United States. Historian Alfred W. Crosby stated in 2003 that the flu originated in Kansas , and author John M. Barry described a January 1918 outbreak in Haskell County, Kansas , as the point of origin in his 2004 article. A 2018 study of tissue slides and medical reports led by evolutionary biology professor Michael Worobey found evidence against the disease originating from Kansas, as those cases were milder and had fewer deaths compared to the infections in New York City in the same period. The study did find evidence through phylogenetic analyses that the virus likely had a North American origin, though it was not conclusive. In addition, the haemagglutinin glycoproteins of the virus suggest that it originated long before 1918, and other studies suggest that the reassortment of the H1N1 virus likely occurred in or around 1915. The major U.K. troop staging and hospital camp in Étaples in France has been theorized by virologist John Oxford as being at the center of the Spanish flu. His study found that in late 1916 the Étaples camp was hit by the onset of a new disease with high mortality that caused symptoms similar to the flu. According to Oxford, a similar outbreak occurred in March 1917 at army barracks in Aldershot , and military pathologists later recognized these early outbreaks as the same disease as the Spanish flu. The overcrowded camp and hospital at Étaples was an ideal environment for the spread of a respiratory virus. The hospital treated thousands of victims of poison gas attacks, and other casualties of war, and 100,000 soldiers passed through the camp every day. It also was home to a piggery and poultry was regularly brought in from surrounding villages to feed the camp. Oxford and his team postulated that a precursor virus, harbored in birds, mutated and then migrated to pigs kept near the front. A report published in 2016 in the Journal of the Chinese Medical Association found evidence that the 1918 virus had been circulating in the European armies for months and possibly years before the 1918 pandemic. Political scientist Andrew Price-Smith published data from the Austrian archives suggesting the influenza began in Austria in early 1917. A 2009 study in Influenza and Other Respiratory Viruses found that Spanish flu mortality simultaneously peaked within the two-month period of October and November 1918 in all fourteen European countries analyzed, which is inconsistent with the pattern that researchers would expect if the virus had originated somewhere in Europe and then spread outwards. In 1993, Claude Hannoun, the leading expert on the Spanish flu at the Pasteur Institute , asserted the precursor virus was likely to have come from China and then mutated in the United States near Boston and from there spread to Brest , France, Europe's battlefields, the rest of Europe, and the rest of the world, with Allied soldiers and sailors as the main disseminators. Hannoun considered several alternative hypotheses of origin, such as Spain, Kansas, and Brest, as being possible, but not likely. In 2014, historian Mark Humphries argued that the mobilization of 96,000 Chinese laborers to work behind the British and French lines might have been the source of the pandemic. Humphries, of the Memorial University of Newfoundland in St. John's , based his conclusions on newly unearthed records. He found archival evidence that a respiratory illness that struck northern China (where the laborers came from) in November 1917 was identified a year later by Chinese health officials as identical to the Spanish flu. Unfortunately, no tissue samples have survived for modern comparison. Nevertheless, there were some reports of respiratory illness on parts of the path the laborers took to get to Europe, which also passed through North America. China was one of the few regions of the world seemingly less affected by the Spanish flu pandemic, where several studies have documented a comparatively mild flu season in 1918. (Although this is disputed due to lack of data during the Warlord Period , see Around the globe .) This has led to speculation that the Spanish flu pandemic originated in China, as the lower rates of flu mortality may be explained by the Chinese population's previously acquired immunity to the flu virus. In the Guangdong Province it was reported that early outbreaks of influenza in 1918 disproportionately impacted young men. The June outbreak infected children and adolescents between 11 and 20 years of age, while the October outbreak was most common in those aged 11 to 15. A report published in 2016 in the Journal of the Chinese Medical Association found no evidence that the 1918 virus was imported to Europe via Chinese and Southeast Asian soldiers and workers and instead found evidence of its circulation in Europe before the pandemic. The 2016 study found that the low flu mortality rate (an estimated one in a thousand) recorded among the Chinese and Southeast Asian workers in Europe suggests that the Asian units were not different from other Allied military units in France at the end of 1918 and, thus, were not a likely source of a new lethal virus. Further evidence against the disease being spread by Chinese workers was that workers entered Europe through other routes that did not result in a detectable spread, making them unlikely to have been the original hosts. The first confirmed cases originated in the United States. Historian Alfred W. Crosby stated in 2003 that the flu originated in Kansas , and author John M. Barry described a January 1918 outbreak in Haskell County, Kansas , as the point of origin in his 2004 article. A 2018 study of tissue slides and medical reports led by evolutionary biology professor Michael Worobey found evidence against the disease originating from Kansas, as those cases were milder and had fewer deaths compared to the infections in New York City in the same period. The study did find evidence through phylogenetic analyses that the virus likely had a North American origin, though it was not conclusive. In addition, the haemagglutinin glycoproteins of the virus suggest that it originated long before 1918, and other studies suggest that the reassortment of the H1N1 virus likely occurred in or around 1915. The major U.K. troop staging and hospital camp in Étaples in France has been theorized by virologist John Oxford as being at the center of the Spanish flu. His study found that in late 1916 the Étaples camp was hit by the onset of a new disease with high mortality that caused symptoms similar to the flu. According to Oxford, a similar outbreak occurred in March 1917 at army barracks in Aldershot , and military pathologists later recognized these early outbreaks as the same disease as the Spanish flu. The overcrowded camp and hospital at Étaples was an ideal environment for the spread of a respiratory virus. The hospital treated thousands of victims of poison gas attacks, and other casualties of war, and 100,000 soldiers passed through the camp every day. It also was home to a piggery and poultry was regularly brought in from surrounding villages to feed the camp. Oxford and his team postulated that a precursor virus, harbored in birds, mutated and then migrated to pigs kept near the front. A report published in 2016 in the Journal of the Chinese Medical Association found evidence that the 1918 virus had been circulating in the European armies for months and possibly years before the 1918 pandemic. Political scientist Andrew Price-Smith published data from the Austrian archives suggesting the influenza began in Austria in early 1917. A 2009 study in Influenza and Other Respiratory Viruses found that Spanish flu mortality simultaneously peaked within the two-month period of October and November 1918 in all fourteen European countries analyzed, which is inconsistent with the pattern that researchers would expect if the virus had originated somewhere in Europe and then spread outwards. In 1993, Claude Hannoun, the leading expert on the Spanish flu at the Pasteur Institute , asserted the precursor virus was likely to have come from China and then mutated in the United States near Boston and from there spread to Brest , France, Europe's battlefields, the rest of Europe, and the rest of the world, with Allied soldiers and sailors as the main disseminators. Hannoun considered several alternative hypotheses of origin, such as Spain, Kansas, and Brest, as being possible, but not likely. In 2014, historian Mark Humphries argued that the mobilization of 96,000 Chinese laborers to work behind the British and French lines might have been the source of the pandemic. Humphries, of the Memorial University of Newfoundland in St. John's , based his conclusions on newly unearthed records. He found archival evidence that a respiratory illness that struck northern China (where the laborers came from) in November 1917 was identified a year later by Chinese health officials as identical to the Spanish flu. Unfortunately, no tissue samples have survived for modern comparison. Nevertheless, there were some reports of respiratory illness on parts of the path the laborers took to get to Europe, which also passed through North America. China was one of the few regions of the world seemingly less affected by the Spanish flu pandemic, where several studies have documented a comparatively mild flu season in 1918. (Although this is disputed due to lack of data during the Warlord Period , see Around the globe .) This has led to speculation that the Spanish flu pandemic originated in China, as the lower rates of flu mortality may be explained by the Chinese population's previously acquired immunity to the flu virus. In the Guangdong Province it was reported that early outbreaks of influenza in 1918 disproportionately impacted young men. The June outbreak infected children and adolescents between 11 and 20 years of age, while the October outbreak was most common in those aged 11 to 15. A report published in 2016 in the Journal of the Chinese Medical Association found no evidence that the 1918 virus was imported to Europe via Chinese and Southeast Asian soldiers and workers and instead found evidence of its circulation in Europe before the pandemic. The 2016 study found that the low flu mortality rate (an estimated one in a thousand) recorded among the Chinese and Southeast Asian workers in Europe suggests that the Asian units were not different from other Allied military units in France at the end of 1918 and, thus, were not a likely source of a new lethal virus. Further evidence against the disease being spread by Chinese workers was that workers entered Europe through other routes that did not result in a detectable spread, making them unlikely to have been the original hosts. The basic reproduction number of the virus was between 2 and 3. The close quarters and massive troop movements of World War I hastened the pandemic, and probably both increased transmission and augmented mutation. The war may also have reduced people's resistance to the virus. Some speculate the soldiers' immune systems were weakened by malnourishment, as well as the stresses of combat and chemical attacks, increasing their susceptibility. A large factor in the worldwide occurrence of the flu was increased travel. Modern transportation systems made it easier for soldiers, sailors, and civilian travelers to spread the disease. Another was lies and denial by governments, leaving the population ill-prepared to handle the outbreaks. The severity of the second wave has been attributed to the circumstances of the First World War. In civilian life, natural selection favors a mild strain. Those who get very ill stay home, and those mildly ill continue with their lives, preferentially spreading the mild strain. In the trenches, natural selection was reversed. Soldiers with a mild strain stayed where they were, while the severely ill were sent on crowded trains to crowded field hospitals, spreading the deadlier virus. The second wave began, and the flu quickly spread around the world again. Consequently, during modern pandemics, health officials look for deadlier strains of a virus when it reaches places with social upheaval. The fact that most of those who recovered from first-wave infections had become immune showed that it must have been the same strain of flu. This was most dramatically illustrated in Copenhagen , which escaped with a combined mortality rate of just 0.29% (0.02% in the first wave and 0.27% in the second wave) because of exposure to the less-lethal first wave. For the rest of the population, the second wave was far more deadly; the most vulnerable people were those like the soldiers in the trenches – adults who were young and fit. After the lethal second wave struck in late 1918, new cases dropped abruptly. In Philadelphia, for example, 4,597 people died in the week ending 16 October, but by 11 November, influenza had almost disappeared from the city. One explanation for the rapid decline in the lethality of the disease is that doctors became more effective in the prevention and treatment of pneumonia that developed after the victims had contracted the virus. However, John Barry stated in his 2004 book The Great Influenza: The Epic Story of the Deadliest Plague In History that researchers have found no evidence to support this position. Another theory holds that the 1918 virus mutated extremely rapidly to a less lethal strain. Such evolution of influenza is a common occurrence: there is a tendency for pathogenic viruses to become less lethal with time, as the hosts of more dangerous strains tend to die out. Fatal cases did continue into 1919, however. One notable example was that of ice hockey player Joe Hall , who, while playing for the Montreal Canadiens , fell victim to the flu in April after an outbreak that resulted in the cancellation of the 1919 Stanley Cup Finals . The majority of the infected experienced only the typical flu symptoms of sore throat, headache, and fever, especially during the first wave. However, during the second wave, the disease was much more serious, often complicated by bacterial pneumonia , which was often the cause of death. This more serious type would cause heliotrope cyanosis to develop, whereby the skin would first develop two mahogany spots over the cheekbones which would then over a few hours spread to color the entire face blue, followed by black coloration first in the extremities and then further spreading to the limbs and the torso. After this, death would follow within hours or days due to the lungs being filled with fluids. Other signs and symptoms reported included spontaneous mouth and nosebleeds, miscarriages for pregnant women, a peculiar smell, teeth and hair falling out, delirium , dizziness, insomnia, loss of hearing or smell, and impaired vision. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes , especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred". The severity of the symptoms was believed to be caused by cytokine storms . The majority of deaths were from bacterial pneumonia , a common secondary infection associated with influenza. This pneumonia was itself caused by common upper respiratory-tract bacteria, which were able to get into the lungs via the damaged bronchial tubes of the victims. The virus also killed people directly by causing massive hemorrhages and edema in the lungs. Modern analysis has shown the virus to be particularly deadly because it triggers a cytokine storm (overreaction of the body's immune system). One group of researchers recovered the virus from the bodies of frozen victims and transfected animals with it. The animals suffered rapidly progressive respiratory failure and death through a cytokine storm. The strong immune reactions of young adults were postulated to have ravaged the body, whereas the weaker immune reactions of children and middle-aged adults resulted in fewer deaths among those groups. Because the virus that caused the disease was too small to be seen under a microscope at the time, there were problems with correctly diagnosing it. The bacterium Haemophilus influenzae was instead mistakenly thought to be the cause, as it was big enough to be seen and was present in many, though not all, patients. For this reason, a vaccine that was used against that bacillus did not make an infection rarer but did decrease the death rate. During the deadly second wave there were also fears that it was in fact plague , dengue fever , or cholera . Another common misdiagnosis was typhus , which was common in circumstances of social upheaval, and was therefore also affecting Russia in the aftermath of the October Revolution . In Chile , the view of the country's elite was that the nation was in severe decline, and therefore doctors assumed that the disease was typhus caused by poor hygiene, and not an infectious one, causing a mismanaged response which did not ban mass gatherings. Studies have shown that the immune system of Spanish flu victims was weakened by adverse climate conditions which were particularly unseasonably cold and wet for extended periods of time during the duration of the pandemic. This affected especially WWI troops exposed to incessant rains and lower-than-average temperatures for the duration of the conflict, and especially during the second wave of the pandemic. Ultra-high-resolution climate data combined with highly detailed mortality records analyzed at Harvard University and the Climate Change Institute at the University of Maine identified a severe climate anomaly that impacted Europe from 1914 to 1919, with several environmental indicators directly influencing the severity and spread of the Spanish flu pandemic. Specifically, a significant increase in precipitation affected all of Europe during the second wave of the pandemic, from September to December 1918. Mortality figures follow closely the concurrent increase in precipitation and decrease in temperatures. Several explanations have been proposed for this, including the fact that lower temperatures and increased precipitation provided ideal conditions for virus replication and transmission, while also negatively affecting the immune systems of soldiers and other people exposed to the inclement weather, a factor proven to increase likelihood of infection by both viruses and pneumococcal co-morbid infections documented to have affected a large percentage of pandemic victims (one fifth of them, with a 36% mortality rate). A six-year climate anomaly (1914–1919) brought cold, marine air to Europe, drastically changing its weather, as documented by eyewitness accounts and instrumental records, reaching as far as the Gallipoli campaign , in Turkey, where ANZAC troops suffered extremely cold temperatures despite the normally Mediterranean climate of the region. The climate anomaly likely influenced the migration of H1N1 avian vectors which contaminate bodies of water with their droppings, reaching 60% infection rates in autumn. The climate anomaly has been associated with an anthropogenic increase in atmospheric dust, due to the incessant bombardment; increased nucleation due to dust particles ( cloud condensation nuclei ) contributed to increased precipitation. The basic reproduction number of the virus was between 2 and 3. The close quarters and massive troop movements of World War I hastened the pandemic, and probably both increased transmission and augmented mutation. The war may also have reduced people's resistance to the virus. Some speculate the soldiers' immune systems were weakened by malnourishment, as well as the stresses of combat and chemical attacks, increasing their susceptibility. A large factor in the worldwide occurrence of the flu was increased travel. Modern transportation systems made it easier for soldiers, sailors, and civilian travelers to spread the disease. Another was lies and denial by governments, leaving the population ill-prepared to handle the outbreaks. The severity of the second wave has been attributed to the circumstances of the First World War. In civilian life, natural selection favors a mild strain. Those who get very ill stay home, and those mildly ill continue with their lives, preferentially spreading the mild strain. In the trenches, natural selection was reversed. Soldiers with a mild strain stayed where they were, while the severely ill were sent on crowded trains to crowded field hospitals, spreading the deadlier virus. The second wave began, and the flu quickly spread around the world again. Consequently, during modern pandemics, health officials look for deadlier strains of a virus when it reaches places with social upheaval. The fact that most of those who recovered from first-wave infections had become immune showed that it must have been the same strain of flu. This was most dramatically illustrated in Copenhagen , which escaped with a combined mortality rate of just 0.29% (0.02% in the first wave and 0.27% in the second wave) because of exposure to the less-lethal first wave. For the rest of the population, the second wave was far more deadly; the most vulnerable people were those like the soldiers in the trenches – adults who were young and fit. After the lethal second wave struck in late 1918, new cases dropped abruptly. In Philadelphia, for example, 4,597 people died in the week ending 16 October, but by 11 November, influenza had almost disappeared from the city. One explanation for the rapid decline in the lethality of the disease is that doctors became more effective in the prevention and treatment of pneumonia that developed after the victims had contracted the virus. However, John Barry stated in his 2004 book The Great Influenza: The Epic Story of the Deadliest Plague In History that researchers have found no evidence to support this position. Another theory holds that the 1918 virus mutated extremely rapidly to a less lethal strain. Such evolution of influenza is a common occurrence: there is a tendency for pathogenic viruses to become less lethal with time, as the hosts of more dangerous strains tend to die out. Fatal cases did continue into 1919, however. One notable example was that of ice hockey player Joe Hall , who, while playing for the Montreal Canadiens , fell victim to the flu in April after an outbreak that resulted in the cancellation of the 1919 Stanley Cup Finals . The majority of the infected experienced only the typical flu symptoms of sore throat, headache, and fever, especially during the first wave. However, during the second wave, the disease was much more serious, often complicated by bacterial pneumonia , which was often the cause of death. This more serious type would cause heliotrope cyanosis to develop, whereby the skin would first develop two mahogany spots over the cheekbones which would then over a few hours spread to color the entire face blue, followed by black coloration first in the extremities and then further spreading to the limbs and the torso. After this, death would follow within hours or days due to the lungs being filled with fluids. Other signs and symptoms reported included spontaneous mouth and nosebleeds, miscarriages for pregnant women, a peculiar smell, teeth and hair falling out, delirium , dizziness, insomnia, loss of hearing or smell, and impaired vision. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes , especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred". The severity of the symptoms was believed to be caused by cytokine storms . The majority of deaths were from bacterial pneumonia , a common secondary infection associated with influenza. This pneumonia was itself caused by common upper respiratory-tract bacteria, which were able to get into the lungs via the damaged bronchial tubes of the victims. The virus also killed people directly by causing massive hemorrhages and edema in the lungs. Modern analysis has shown the virus to be particularly deadly because it triggers a cytokine storm (overreaction of the body's immune system). One group of researchers recovered the virus from the bodies of frozen victims and transfected animals with it. The animals suffered rapidly progressive respiratory failure and death through a cytokine storm. The strong immune reactions of young adults were postulated to have ravaged the body, whereas the weaker immune reactions of children and middle-aged adults resulted in fewer deaths among those groups. Because the virus that caused the disease was too small to be seen under a microscope at the time, there were problems with correctly diagnosing it. The bacterium Haemophilus influenzae was instead mistakenly thought to be the cause, as it was big enough to be seen and was present in many, though not all, patients. For this reason, a vaccine that was used against that bacillus did not make an infection rarer but did decrease the death rate. During the deadly second wave there were also fears that it was in fact plague , dengue fever , or cholera . Another common misdiagnosis was typhus , which was common in circumstances of social upheaval, and was therefore also affecting Russia in the aftermath of the October Revolution . In Chile , the view of the country's elite was that the nation was in severe decline, and therefore doctors assumed that the disease was typhus caused by poor hygiene, and not an infectious one, causing a mismanaged response which did not ban mass gatherings. Studies have shown that the immune system of Spanish flu victims was weakened by adverse climate conditions which were particularly unseasonably cold and wet for extended periods of time during the duration of the pandemic. This affected especially WWI troops exposed to incessant rains and lower-than-average temperatures for the duration of the conflict, and especially during the second wave of the pandemic. Ultra-high-resolution climate data combined with highly detailed mortality records analyzed at Harvard University and the Climate Change Institute at the University of Maine identified a severe climate anomaly that impacted Europe from 1914 to 1919, with several environmental indicators directly influencing the severity and spread of the Spanish flu pandemic. Specifically, a significant increase in precipitation affected all of Europe during the second wave of the pandemic, from September to December 1918. Mortality figures follow closely the concurrent increase in precipitation and decrease in temperatures. Several explanations have been proposed for this, including the fact that lower temperatures and increased precipitation provided ideal conditions for virus replication and transmission, while also negatively affecting the immune systems of soldiers and other people exposed to the inclement weather, a factor proven to increase likelihood of infection by both viruses and pneumococcal co-morbid infections documented to have affected a large percentage of pandemic victims (one fifth of them, with a 36% mortality rate). A six-year climate anomaly (1914–1919) brought cold, marine air to Europe, drastically changing its weather, as documented by eyewitness accounts and instrumental records, reaching as far as the Gallipoli campaign , in Turkey, where ANZAC troops suffered extremely cold temperatures despite the normally Mediterranean climate of the region. The climate anomaly likely influenced the migration of H1N1 avian vectors which contaminate bodies of water with their droppings, reaching 60% infection rates in autumn. The climate anomaly has been associated with an anthropogenic increase in atmospheric dust, due to the incessant bombardment; increased nucleation due to dust particles ( cloud condensation nuclei ) contributed to increased precipitation. While systems for alerting public health authorities of infectious spread did exist in 1918, they did not generally include influenza, leading to a delayed response. Nevertheless, actions were taken. Maritime quarantines were declared on islands such as Iceland, Australia, and American Samoa, saving many lives. Social distancing measures were introduced, for example closing schools, theatres, and places of worship, limiting public transportation, and banning mass gatherings. Wearing face masks became common in some places, such as Japan, though there were debates over their efficacy. There was also some resistance to their use, as exemplified by the Anti-Mask League of San Francisco . Vaccines were also developed, but as these were based on bacteria and not the actual virus, they could only help with secondary infections. The actual enforcement of various restrictions varied. To a large extent, the New York City health commissioner ordered businesses to open and close on staggered shifts to avoid overcrowding on the subways. A later study found that measures such as banning mass gatherings and requiring the wearing of face masks could cut the death rate up to 50 percent, but this was dependent on their being imposed early in the outbreak and not being lifted prematurely. As there were no antiviral drugs to treat the virus, and no antibiotics to treat the secondary bacterial infections, doctors would rely on a random assortment of medicines with varying degrees of effectiveness, such as aspirin , quinine , arsenics , digitalis , strychnine , epsom salts , castor oil , and iodine . Treatments of traditional medicine , such as bloodletting , ayurveda , and kampo were also applied. Due to World War I , many countries engaged in wartime censorship, and suppressed reporting of the pandemic. For example, the Italian newspaper Corriere della Sera was prohibited from reporting daily death tolls. The newspapers of the time were also generally paternalistic and worried about mass panic. Misinformation also spread along with the disease. In Ireland there was a belief that noxious gases were rising from the mass graves of Flanders Fields and being "blown all over the world by winds". There were also rumors that the Germans were behind it, for example by poisoning the aspirin manufactured by Bayer , or by releasing poison gas from U-boats . While systems for alerting public health authorities of infectious spread did exist in 1918, they did not generally include influenza, leading to a delayed response. Nevertheless, actions were taken. Maritime quarantines were declared on islands such as Iceland, Australia, and American Samoa, saving many lives. Social distancing measures were introduced, for example closing schools, theatres, and places of worship, limiting public transportation, and banning mass gatherings. Wearing face masks became common in some places, such as Japan, though there were debates over their efficacy. There was also some resistance to their use, as exemplified by the Anti-Mask League of San Francisco . Vaccines were also developed, but as these were based on bacteria and not the actual virus, they could only help with secondary infections. The actual enforcement of various restrictions varied. To a large extent, the New York City health commissioner ordered businesses to open and close on staggered shifts to avoid overcrowding on the subways. A later study found that measures such as banning mass gatherings and requiring the wearing of face masks could cut the death rate up to 50 percent, but this was dependent on their being imposed early in the outbreak and not being lifted prematurely. As there were no antiviral drugs to treat the virus, and no antibiotics to treat the secondary bacterial infections, doctors would rely on a random assortment of medicines with varying degrees of effectiveness, such as aspirin , quinine , arsenics , digitalis , strychnine , epsom salts , castor oil , and iodine . Treatments of traditional medicine , such as bloodletting , ayurveda , and kampo were also applied. Due to World War I , many countries engaged in wartime censorship, and suppressed reporting of the pandemic. For example, the Italian newspaper Corriere della Sera was prohibited from reporting daily death tolls. The newspapers of the time were also generally paternalistic and worried about mass panic. Misinformation also spread along with the disease. In Ireland there was a belief that noxious gases were rising from the mass graves of Flanders Fields and being "blown all over the world by winds". There were also rumors that the Germans were behind it, for example by poisoning the aspirin manufactured by Bayer , or by releasing poison gas from U-boats . The Spanish flu infected around 500 million people, about one-third of the world's population. Estimates as to how many infected people died vary greatly, but the flu is regardless considered to be one of the deadliest pandemics in history. An early estimate from 1927 put global mortality at 21.6 million. An estimate from 1991 states that the virus killed between 25 and 39 million people. A 2005 estimate put the death toll at 50 million (about 3% of the global population), and possibly as high as 100 million (more than 5%). However, a 2018 reassessment in the American Journal of Epidemiology estimated the total to be about 17 million, though this has been contested. With a world population of 1.8 to 1.9 billion, these estimates correspond to between 1 and 6 percent of the population. A 2009 study in Influenza and Other Respiratory Viruses based on data from fourteen European countries estimated a total of 2.64 million excess deaths in Europe attributable to the Spanish flu during the major 1918–1919 phase of the pandemic, in line with the three prior studies from 1991, 2002, and 2006 that calculated a European death toll of between 2 million and 2.3 million. This represents a mortality rate of about 1.1% of the European population ( c. 250 million in 1918), considerably higher than the mortality rate in the U.S., which the authors hypothesize is likely due to the severe effects of the war in Europe. The excess mortality rate in the U.K. has been estimated at 0.28%–0.4%, far below this European average. Some 12–17 million people died in India , about 5% of the population. The death toll in India's British-ruled districts was 13.88 million. Another estimate gives at least 12 million dead. The decade between 1911 and 1921 was the only census period in which India's population fell, mostly due to devastation of the Spanish flu pandemic. While India is generally described as the country most severely affected by the Spanish flu, at least one study argues that other factors may partially account for the very high excess mortality rates observed in 1918, citing unusually high 1917 mortality and wide regional variation (ranging from 0.47% to 6.66%). A 2006 study in The Lancet also noted that Indian provinces had excess mortality rates ranging from 2.1% to 7.8%, stating: "Commentators at the time attributed this huge variation to differences in nutritional status and diurnal fluctuations in temperature." In Finland, 20,000 died out of 210,000 infected. In Sweden, 34,000 died. In Japan, the flu killed nearly 500,000 people over two waves between 1918 and 1920, with nearly 300,000 excess deaths between October 1918 and May 1919 and 182,000 between December 1919 and May 1920. In the Dutch East Indies (now Indonesia ), 1.5 million were assumed to have died among 30 million inhabitants. In Tahiti , 13% of the population died during one month. Similarly, in Western Samoa 22% of the population of 38,000 died within two months. In Istanbul , capital of the Ottoman Empire, 6,403 to 10,000 died, giving the city a mortality rate of at least 0.56%. In New Zealand, the flu killed an estimated 6,400 Pākehā (or "New Zealanders primarily of European descent") and 2,500 indigenous Māori in six weeks, with Māori dying at eight times the rate of Pākehā. In Australia, the flu killed around 12,000 to 20,000 people. The country's death rate, 2.7 per 1,000 people, was one of the lowest recorded compared with other countries at the time; however, as much as 40 percent of the population were infected, and a mortality rate of 50 percent was recorded by some Aboriginal communities. New South Wales and Victoria saw the greatest relative mortality, with 3.19 and 2.40 deaths per 1,000 people respectively, while Western Australia, Queensland, Southern Australia, and Tasmania experienced rates of 1.70, 1.14, 1.13, and 1.09 per 1,000 respectively. In Queensland, at least one-third of deaths recorded were in the Aboriginal population. In the U.S., about 28% of the population of 105 million became infected, and 500,000 to 850,000 died (0.48 to 0.81 percent of the population). Native American tribes were particularly hard hit. In the Four Corners area, there were 3,293 registered deaths among Native Americans . Entire Inuit and Alaskan Native village communities died in Alaska . In Canada, 50,000 died. In Brazil, 300,000 died, including president Rodrigues Alves . In the UK, as many as 250,000 died; in France, more than 400,000. In Ghana , the influenza epidemic killed at least 100,000 people. Tafari Makonnen (the future Haile Selassie , Emperor of Ethiopia ) was one of the first Ethiopians who contracted influenza but survived. Many of his subjects did not; estimates for fatalities in the capital city, Addis Ababa , range from 5,000 to 10,000, or higher. The death toll in Russia has been estimated at 450,000, though the epidemiologists who suggested this number called it a "shot in the dark". If it is correct, Russia lost roughly 0.4% of its population, meaning it suffered the lowest influenza-related mortality in Europe. Another study considers this number unlikely, given that the country was in the grip of a civil war , and the infrastructure of daily life had broken down; the study suggests that Russia's death toll was closer to 2%, or 2.7 million people. Even in areas where mortality was low, so many adults were incapacitated that much of everyday life was hampered. Some communities closed all stores or required customers to leave orders outside. There were reports that healthcare workers could not tend the sick nor the gravediggers bury the dead because they too were ill. Mass graves were dug by steam shovel and bodies buried without coffins in many places. Bristol Bay , a region of Alaska populated by indigenous people , suffered a death rate of 40 percent of the total population, with some villages entirely disappearing. Nenana, Alaska , managed to avoid the extent of the pandemic between 1918 and 1919, but the flu at last reached the town in spring 1920. Reports suggested that during the first two weeks of May, the majority of the town's population became infected; 10% of the population were estimated to have died, most of whom were Alaska Natives. Several Pacific island territories were hit particularly hard. The pandemic reached them from New Zealand, which was too slow to implement measures to prevent ships, such as Talune , carrying the flu from leaving its ports. From New Zealand, the flu reached Tonga (killing 8% of the population), Nauru (16%), and Fiji (5%, 9,000 people). Worst affected was Western Samoa, formerly German Samoa , which had been occupied by New Zealand in 1914. 90% of the population was infected; 30% of adult men, 22% of adult women, and 10% of children died. By contrast, Governor John Martin Poyer prevented the flu from reaching neighboring American Samoa by imposing a blockade. The disease spread fastest through the higher social classes among the indigenous peoples, because of the custom of gathering oral tradition from chiefs on their deathbeds; many community elders were infected through this process. In Iran , the mortality was very high: according to an estimate, between 902,400 and 2,431,000, or 8% to 22% of the total population died. The country was going through the Persian famine of 1917–1919 concurrently. In Ireland , during the worst 12 months, the Spanish flu accounted for one-third of all deaths. In South Africa it is estimated that about 300,000 people amounting to 6% of the population died within six weeks. Government actions in the early stages of the virus' arrival in the country in September 1918 are believed to have unintentionally accelerated its spread throughout the country. Almost a quarter of the working population of Kimberley , consisting of workers in the diamond mines, died. In British Somaliland , one official estimated that 7% of the native population died. This huge death toll resulted from an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms . In the Pacific, American Samoa and the French colony of New Caledonia succeeded in preventing even a single death from influenza through effective quarantines . However, the outbreak was delayed into 1926 for American Samoa and 1921 for New Caledonia as the quarantine period ended. On American Samoa, at least 25% of the island residents were clinically attacked and 0.1% died, and on New Caledonia, there was widespread illness and 0.1% population died. Australia also managed to avoid the first two waves with a quarantine. Iceland protected a third of its population from exposure by blocking the main road of the island. By the end of the pandemic, the isolated island of Marajó , in Brazil's Amazon River Delta had not reported an outbreak. Saint Helena also reported no deaths. Estimates for the death toll in China have varied widely, a range which reflects the lack of centralized collection of health data at the time due to the Warlord period . China may have experienced a relatively mild flu season in 1918 compared to other areas of the world. However, some reports from its interior suggest that mortality rates from influenza were perhaps higher in at least a few locations in China in 1918. At the very least, there is little evidence that China as a whole was seriously affected by the flu compared to other countries in the world. The first estimate of the Chinese death toll was made in 1991 by Patterson and Pyle, which estimated a toll of between 5 and 9 million. However, this 1991 study was criticized by later studies due to flawed methodology, and newer studies have published estimates of a far lower mortality rate in China. For instance, Iijima in 1998 estimates the death toll in China to be between 1 and 1.28 million based on data available from Chinese port cities. The lower estimates of the Chinese death toll are based on the low mortality rates that were found in Chinese port cities (for example, Hong Kong) and on the assumption that poor communications prevented the flu from penetrating the interior of China. However, some contemporary newspaper and post office reports, as well as reports from missionary doctors, suggest that the flu did penetrate the Chinese interior and that influenza was severe in at least some locations in the countryside of China. Although medical records from China's interior are lacking, extensive medical data were recorded in Chinese port cities, such as then British -controlled Hong Kong, Canton , Peking , Harbin and Shanghai . These data were collected by the Chinese Maritime Customs Service , which was largely staffed by non-Chinese foreigners, such as the British, French, and other European colonial officials in China. As a whole, data from China's port cities show low mortality rates compared to other cities in Asia. For example, the British authorities at Hong Kong and Canton reported a mortality rate from influenza at a rate of 0.25% and 0.32%, much lower than the reported mortality rate of other cities in Asia, such as Calcutta or Bombay, where influenza was much more devastating. Similarly, in the city of Shanghai – which had a population of over 2 million in 1918 – there were only 266 recorded deaths from influenza among the Chinese population in 1918. If extrapolated from the extensive data recorded from Chinese cities, the suggested mortality rate from influenza in China as a whole in 1918 was likely lower than 1% – much lower than the world average (which was around 3–5%). In contrast, Japan and Taiwan had reported a mortality rate from influenza around 0.45% and 0.69% respectively, higher than the mortality rate collected from data in Chinese port cities, such as Hong Kong (0.25%), Canton (0.32%), and Shanghai. However, it is noted that the influenza mortality rate in Hong Kong and Canton are under-recorded, because only the deaths that occurred in colony hospitals were counted. Similarly, in Shanghai, these statistics are limited to that area of the city under the control of the health section of the Shanghai International Settlement, and the actual death toll in Shanghai was much higher. The medical records from China's interior indicate that, compared to cities, rural communities have substantially higher mortality rate. A published influenza survey in Houlu County, Hebei Province, found that the case fatality rate was 9.77% and 0.79% of county population died from influenza in October and November 1918. The pandemic mostly killed young adults. In 1918–1919, 99% of pandemic influenza deaths in the U.S. occurred in people under 65, and nearly half of deaths were in young adults 20 to 40 years old. In 1920, the mortality rate among people under 65 had decreased sixfold to half the mortality rate of people over 65, but 92% of deaths still occurred in people under 65. This is unusual since influenza is typically most deadly to weak individuals, such as infants under age two, adults over age 70, and the immunocompromised . In 1918, older adults may have had partial protection caused by exposure to the 1889–1890 flu pandemic, known as the "Russian flu". According to historian John M. Barry, the most vulnerable of all – "those most likely, of the most likely", to die – were pregnant women. He reported that in thirteen studies of hospitalized women in the pandemic, the death rate ranged from 23% to 71%. Of the pregnant women who survived childbirth, over one-quarter (26%) lost the child. Another oddity was that the outbreak was widespread in the summer and autumn (in the Northern Hemisphere); influenza is usually worse in winter. There were also geographic patterns to the disease's fatality. Some parts of Asia had 30 times higher death rates than some parts of Europe, and generally, Africa and Asia had higher rates, while Europe and North America had lower ones. There was also great variation within continents, with three times higher mortality in Hungary and Spain compared to Denmark, two to three times higher chance of death in Sub-Saharan Africa compared to North Africa, and possibly up to ten times higher rates between the extremes of Asia. Cities were affected worse than rural areas. There were also differences between cities, which might have reflected exposure to the milder first wave giving immunity, as well as the introduction of social distancing measures. Another major pattern was the differences between social classes. In Oslo , death rates were inversely correlated with apartment size, as the poorer people living in smaller apartments died at a higher rate. Social status was also reflected in the higher mortality among immigrant communities, with Italian Americans , a recently arrived group at the time, were nearly twice as likely to die compared to the average Americans. These disparities reflected worse diets, crowded living conditions, and problems accessing healthcare. Paradoxically, however, African Americans were relatively spared by the pandemic. More men than women were killed by the flu, as they were more likely to go out and be exposed, while women would tend to stay at home . For the same reason men also were more likely to have pre-existing tuberculosis , which severely worsened the chances of recovery. However, in India the opposite was true, potentially because Indian women were neglected with poorer nutrition, and were expected to care for the sick. A study conducted by He et al . (2011) used a mechanistic modeling approach to study the three waves of the 1918 influenza pandemic. They examined the factors that underlie variability in temporal patterns and their correlation to patterns of mortality and morbidity. Their analysis suggests that temporal variations in transmission rate provide the best explanation, and the variation in transmission required to generate these three waves is within biologically plausible values. Another study by He et al . (2013) used a simple epidemic model incorporating three factors to infer the cause of the three waves of the 1918 influenza pandemic. These factors were school opening and closing, temperature changes throughout the outbreak, and human behavioral changes in response to the outbreak. Their modeling results showed that all three factors are important, but human behavioral responses showed the most significant effects. The Spanish flu infected around 500 million people, about one-third of the world's population. Estimates as to how many infected people died vary greatly, but the flu is regardless considered to be one of the deadliest pandemics in history. An early estimate from 1927 put global mortality at 21.6 million. An estimate from 1991 states that the virus killed between 25 and 39 million people. A 2005 estimate put the death toll at 50 million (about 3% of the global population), and possibly as high as 100 million (more than 5%). However, a 2018 reassessment in the American Journal of Epidemiology estimated the total to be about 17 million, though this has been contested. With a world population of 1.8 to 1.9 billion, these estimates correspond to between 1 and 6 percent of the population. A 2009 study in Influenza and Other Respiratory Viruses based on data from fourteen European countries estimated a total of 2.64 million excess deaths in Europe attributable to the Spanish flu during the major 1918–1919 phase of the pandemic, in line with the three prior studies from 1991, 2002, and 2006 that calculated a European death toll of between 2 million and 2.3 million. This represents a mortality rate of about 1.1% of the European population ( c. 250 million in 1918), considerably higher than the mortality rate in the U.S., which the authors hypothesize is likely due to the severe effects of the war in Europe. The excess mortality rate in the U.K. has been estimated at 0.28%–0.4%, far below this European average. Some 12–17 million people died in India , about 5% of the population. The death toll in India's British-ruled districts was 13.88 million. Another estimate gives at least 12 million dead. The decade between 1911 and 1921 was the only census period in which India's population fell, mostly due to devastation of the Spanish flu pandemic. While India is generally described as the country most severely affected by the Spanish flu, at least one study argues that other factors may partially account for the very high excess mortality rates observed in 1918, citing unusually high 1917 mortality and wide regional variation (ranging from 0.47% to 6.66%). A 2006 study in The Lancet also noted that Indian provinces had excess mortality rates ranging from 2.1% to 7.8%, stating: "Commentators at the time attributed this huge variation to differences in nutritional status and diurnal fluctuations in temperature." In Finland, 20,000 died out of 210,000 infected. In Sweden, 34,000 died. In Japan, the flu killed nearly 500,000 people over two waves between 1918 and 1920, with nearly 300,000 excess deaths between October 1918 and May 1919 and 182,000 between December 1919 and May 1920. In the Dutch East Indies (now Indonesia ), 1.5 million were assumed to have died among 30 million inhabitants. In Tahiti , 13% of the population died during one month. Similarly, in Western Samoa 22% of the population of 38,000 died within two months. In Istanbul , capital of the Ottoman Empire, 6,403 to 10,000 died, giving the city a mortality rate of at least 0.56%. In New Zealand, the flu killed an estimated 6,400 Pākehā (or "New Zealanders primarily of European descent") and 2,500 indigenous Māori in six weeks, with Māori dying at eight times the rate of Pākehā. In Australia, the flu killed around 12,000 to 20,000 people. The country's death rate, 2.7 per 1,000 people, was one of the lowest recorded compared with other countries at the time; however, as much as 40 percent of the population were infected, and a mortality rate of 50 percent was recorded by some Aboriginal communities. New South Wales and Victoria saw the greatest relative mortality, with 3.19 and 2.40 deaths per 1,000 people respectively, while Western Australia, Queensland, Southern Australia, and Tasmania experienced rates of 1.70, 1.14, 1.13, and 1.09 per 1,000 respectively. In Queensland, at least one-third of deaths recorded were in the Aboriginal population. In the U.S., about 28% of the population of 105 million became infected, and 500,000 to 850,000 died (0.48 to 0.81 percent of the population). Native American tribes were particularly hard hit. In the Four Corners area, there were 3,293 registered deaths among Native Americans . Entire Inuit and Alaskan Native village communities died in Alaska . In Canada, 50,000 died. In Brazil, 300,000 died, including president Rodrigues Alves . In the UK, as many as 250,000 died; in France, more than 400,000. In Ghana , the influenza epidemic killed at least 100,000 people. Tafari Makonnen (the future Haile Selassie , Emperor of Ethiopia ) was one of the first Ethiopians who contracted influenza but survived. Many of his subjects did not; estimates for fatalities in the capital city, Addis Ababa , range from 5,000 to 10,000, or higher. The death toll in Russia has been estimated at 450,000, though the epidemiologists who suggested this number called it a "shot in the dark". If it is correct, Russia lost roughly 0.4% of its population, meaning it suffered the lowest influenza-related mortality in Europe. Another study considers this number unlikely, given that the country was in the grip of a civil war , and the infrastructure of daily life had broken down; the study suggests that Russia's death toll was closer to 2%, or 2.7 million people. Even in areas where mortality was low, so many adults were incapacitated that much of everyday life was hampered. Some communities closed all stores or required customers to leave orders outside. There were reports that healthcare workers could not tend the sick nor the gravediggers bury the dead because they too were ill. Mass graves were dug by steam shovel and bodies buried without coffins in many places. Bristol Bay , a region of Alaska populated by indigenous people , suffered a death rate of 40 percent of the total population, with some villages entirely disappearing. Nenana, Alaska , managed to avoid the extent of the pandemic between 1918 and 1919, but the flu at last reached the town in spring 1920. Reports suggested that during the first two weeks of May, the majority of the town's population became infected; 10% of the population were estimated to have died, most of whom were Alaska Natives. Several Pacific island territories were hit particularly hard. The pandemic reached them from New Zealand, which was too slow to implement measures to prevent ships, such as Talune , carrying the flu from leaving its ports. From New Zealand, the flu reached Tonga (killing 8% of the population), Nauru (16%), and Fiji (5%, 9,000 people). Worst affected was Western Samoa, formerly German Samoa , which had been occupied by New Zealand in 1914. 90% of the population was infected; 30% of adult men, 22% of adult women, and 10% of children died. By contrast, Governor John Martin Poyer prevented the flu from reaching neighboring American Samoa by imposing a blockade. The disease spread fastest through the higher social classes among the indigenous peoples, because of the custom of gathering oral tradition from chiefs on their deathbeds; many community elders were infected through this process. In Iran , the mortality was very high: according to an estimate, between 902,400 and 2,431,000, or 8% to 22% of the total population died. The country was going through the Persian famine of 1917–1919 concurrently. In Ireland , during the worst 12 months, the Spanish flu accounted for one-third of all deaths. In South Africa it is estimated that about 300,000 people amounting to 6% of the population died within six weeks. Government actions in the early stages of the virus' arrival in the country in September 1918 are believed to have unintentionally accelerated its spread throughout the country. Almost a quarter of the working population of Kimberley , consisting of workers in the diamond mines, died. In British Somaliland , one official estimated that 7% of the native population died. This huge death toll resulted from an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms . In the Pacific, American Samoa and the French colony of New Caledonia succeeded in preventing even a single death from influenza through effective quarantines . However, the outbreak was delayed into 1926 for American Samoa and 1921 for New Caledonia as the quarantine period ended. On American Samoa, at least 25% of the island residents were clinically attacked and 0.1% died, and on New Caledonia, there was widespread illness and 0.1% population died. Australia also managed to avoid the first two waves with a quarantine. Iceland protected a third of its population from exposure by blocking the main road of the island. By the end of the pandemic, the isolated island of Marajó , in Brazil's Amazon River Delta had not reported an outbreak. Saint Helena also reported no deaths. Estimates for the death toll in China have varied widely, a range which reflects the lack of centralized collection of health data at the time due to the Warlord period . China may have experienced a relatively mild flu season in 1918 compared to other areas of the world. However, some reports from its interior suggest that mortality rates from influenza were perhaps higher in at least a few locations in China in 1918. At the very least, there is little evidence that China as a whole was seriously affected by the flu compared to other countries in the world. The first estimate of the Chinese death toll was made in 1991 by Patterson and Pyle, which estimated a toll of between 5 and 9 million. However, this 1991 study was criticized by later studies due to flawed methodology, and newer studies have published estimates of a far lower mortality rate in China. For instance, Iijima in 1998 estimates the death toll in China to be between 1 and 1.28 million based on data available from Chinese port cities. The lower estimates of the Chinese death toll are based on the low mortality rates that were found in Chinese port cities (for example, Hong Kong) and on the assumption that poor communications prevented the flu from penetrating the interior of China. However, some contemporary newspaper and post office reports, as well as reports from missionary doctors, suggest that the flu did penetrate the Chinese interior and that influenza was severe in at least some locations in the countryside of China. Although medical records from China's interior are lacking, extensive medical data were recorded in Chinese port cities, such as then British -controlled Hong Kong, Canton , Peking , Harbin and Shanghai . These data were collected by the Chinese Maritime Customs Service , which was largely staffed by non-Chinese foreigners, such as the British, French, and other European colonial officials in China. As a whole, data from China's port cities show low mortality rates compared to other cities in Asia. For example, the British authorities at Hong Kong and Canton reported a mortality rate from influenza at a rate of 0.25% and 0.32%, much lower than the reported mortality rate of other cities in Asia, such as Calcutta or Bombay, where influenza was much more devastating. Similarly, in the city of Shanghai – which had a population of over 2 million in 1918 – there were only 266 recorded deaths from influenza among the Chinese population in 1918. If extrapolated from the extensive data recorded from Chinese cities, the suggested mortality rate from influenza in China as a whole in 1918 was likely lower than 1% – much lower than the world average (which was around 3–5%). In contrast, Japan and Taiwan had reported a mortality rate from influenza around 0.45% and 0.69% respectively, higher than the mortality rate collected from data in Chinese port cities, such as Hong Kong (0.25%), Canton (0.32%), and Shanghai. However, it is noted that the influenza mortality rate in Hong Kong and Canton are under-recorded, because only the deaths that occurred in colony hospitals were counted. Similarly, in Shanghai, these statistics are limited to that area of the city under the control of the health section of the Shanghai International Settlement, and the actual death toll in Shanghai was much higher. The medical records from China's interior indicate that, compared to cities, rural communities have substantially higher mortality rate. A published influenza survey in Houlu County, Hebei Province, found that the case fatality rate was 9.77% and 0.79% of county population died from influenza in October and November 1918. Even in areas where mortality was low, so many adults were incapacitated that much of everyday life was hampered. Some communities closed all stores or required customers to leave orders outside. There were reports that healthcare workers could not tend the sick nor the gravediggers bury the dead because they too were ill. Mass graves were dug by steam shovel and bodies buried without coffins in many places. Bristol Bay , a region of Alaska populated by indigenous people , suffered a death rate of 40 percent of the total population, with some villages entirely disappearing. Nenana, Alaska , managed to avoid the extent of the pandemic between 1918 and 1919, but the flu at last reached the town in spring 1920. Reports suggested that during the first two weeks of May, the majority of the town's population became infected; 10% of the population were estimated to have died, most of whom were Alaska Natives. Several Pacific island territories were hit particularly hard. The pandemic reached them from New Zealand, which was too slow to implement measures to prevent ships, such as Talune , carrying the flu from leaving its ports. From New Zealand, the flu reached Tonga (killing 8% of the population), Nauru (16%), and Fiji (5%, 9,000 people). Worst affected was Western Samoa, formerly German Samoa , which had been occupied by New Zealand in 1914. 90% of the population was infected; 30% of adult men, 22% of adult women, and 10% of children died. By contrast, Governor John Martin Poyer prevented the flu from reaching neighboring American Samoa by imposing a blockade. The disease spread fastest through the higher social classes among the indigenous peoples, because of the custom of gathering oral tradition from chiefs on their deathbeds; many community elders were infected through this process. In Iran , the mortality was very high: according to an estimate, between 902,400 and 2,431,000, or 8% to 22% of the total population died. The country was going through the Persian famine of 1917–1919 concurrently. In Ireland , during the worst 12 months, the Spanish flu accounted for one-third of all deaths. In South Africa it is estimated that about 300,000 people amounting to 6% of the population died within six weeks. Government actions in the early stages of the virus' arrival in the country in September 1918 are believed to have unintentionally accelerated its spread throughout the country. Almost a quarter of the working population of Kimberley , consisting of workers in the diamond mines, died. In British Somaliland , one official estimated that 7% of the native population died. This huge death toll resulted from an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms . In the Pacific, American Samoa and the French colony of New Caledonia succeeded in preventing even a single death from influenza through effective quarantines . However, the outbreak was delayed into 1926 for American Samoa and 1921 for New Caledonia as the quarantine period ended. On American Samoa, at least 25% of the island residents were clinically attacked and 0.1% died, and on New Caledonia, there was widespread illness and 0.1% population died. Australia also managed to avoid the first two waves with a quarantine. Iceland protected a third of its population from exposure by blocking the main road of the island. By the end of the pandemic, the isolated island of Marajó , in Brazil's Amazon River Delta had not reported an outbreak. Saint Helena also reported no deaths. Estimates for the death toll in China have varied widely, a range which reflects the lack of centralized collection of health data at the time due to the Warlord period . China may have experienced a relatively mild flu season in 1918 compared to other areas of the world. However, some reports from its interior suggest that mortality rates from influenza were perhaps higher in at least a few locations in China in 1918. At the very least, there is little evidence that China as a whole was seriously affected by the flu compared to other countries in the world. The first estimate of the Chinese death toll was made in 1991 by Patterson and Pyle, which estimated a toll of between 5 and 9 million. However, this 1991 study was criticized by later studies due to flawed methodology, and newer studies have published estimates of a far lower mortality rate in China. For instance, Iijima in 1998 estimates the death toll in China to be between 1 and 1.28 million based on data available from Chinese port cities. The lower estimates of the Chinese death toll are based on the low mortality rates that were found in Chinese port cities (for example, Hong Kong) and on the assumption that poor communications prevented the flu from penetrating the interior of China. However, some contemporary newspaper and post office reports, as well as reports from missionary doctors, suggest that the flu did penetrate the Chinese interior and that influenza was severe in at least some locations in the countryside of China. Although medical records from China's interior are lacking, extensive medical data were recorded in Chinese port cities, such as then British -controlled Hong Kong, Canton , Peking , Harbin and Shanghai . These data were collected by the Chinese Maritime Customs Service , which was largely staffed by non-Chinese foreigners, such as the British, French, and other European colonial officials in China. As a whole, data from China's port cities show low mortality rates compared to other cities in Asia. For example, the British authorities at Hong Kong and Canton reported a mortality rate from influenza at a rate of 0.25% and 0.32%, much lower than the reported mortality rate of other cities in Asia, such as Calcutta or Bombay, where influenza was much more devastating. Similarly, in the city of Shanghai – which had a population of over 2 million in 1918 – there were only 266 recorded deaths from influenza among the Chinese population in 1918. If extrapolated from the extensive data recorded from Chinese cities, the suggested mortality rate from influenza in China as a whole in 1918 was likely lower than 1% – much lower than the world average (which was around 3–5%). In contrast, Japan and Taiwan had reported a mortality rate from influenza around 0.45% and 0.69% respectively, higher than the mortality rate collected from data in Chinese port cities, such as Hong Kong (0.25%), Canton (0.32%), and Shanghai. However, it is noted that the influenza mortality rate in Hong Kong and Canton are under-recorded, because only the deaths that occurred in colony hospitals were counted. Similarly, in Shanghai, these statistics are limited to that area of the city under the control of the health section of the Shanghai International Settlement, and the actual death toll in Shanghai was much higher. The medical records from China's interior indicate that, compared to cities, rural communities have substantially higher mortality rate. A published influenza survey in Houlu County, Hebei Province, found that the case fatality rate was 9.77% and 0.79% of county population died from influenza in October and November 1918. The pandemic mostly killed young adults. In 1918–1919, 99% of pandemic influenza deaths in the U.S. occurred in people under 65, and nearly half of deaths were in young adults 20 to 40 years old. In 1920, the mortality rate among people under 65 had decreased sixfold to half the mortality rate of people over 65, but 92% of deaths still occurred in people under 65. This is unusual since influenza is typically most deadly to weak individuals, such as infants under age two, adults over age 70, and the immunocompromised . In 1918, older adults may have had partial protection caused by exposure to the 1889–1890 flu pandemic, known as the "Russian flu". According to historian John M. Barry, the most vulnerable of all – "those most likely, of the most likely", to die – were pregnant women. He reported that in thirteen studies of hospitalized women in the pandemic, the death rate ranged from 23% to 71%. Of the pregnant women who survived childbirth, over one-quarter (26%) lost the child. Another oddity was that the outbreak was widespread in the summer and autumn (in the Northern Hemisphere); influenza is usually worse in winter. There were also geographic patterns to the disease's fatality. Some parts of Asia had 30 times higher death rates than some parts of Europe, and generally, Africa and Asia had higher rates, while Europe and North America had lower ones. There was also great variation within continents, with three times higher mortality in Hungary and Spain compared to Denmark, two to three times higher chance of death in Sub-Saharan Africa compared to North Africa, and possibly up to ten times higher rates between the extremes of Asia. Cities were affected worse than rural areas. There were also differences between cities, which might have reflected exposure to the milder first wave giving immunity, as well as the introduction of social distancing measures. Another major pattern was the differences between social classes. In Oslo , death rates were inversely correlated with apartment size, as the poorer people living in smaller apartments died at a higher rate. Social status was also reflected in the higher mortality among immigrant communities, with Italian Americans , a recently arrived group at the time, were nearly twice as likely to die compared to the average Americans. These disparities reflected worse diets, crowded living conditions, and problems accessing healthcare. Paradoxically, however, African Americans were relatively spared by the pandemic. More men than women were killed by the flu, as they were more likely to go out and be exposed, while women would tend to stay at home . For the same reason men also were more likely to have pre-existing tuberculosis , which severely worsened the chances of recovery. However, in India the opposite was true, potentially because Indian women were neglected with poorer nutrition, and were expected to care for the sick. A study conducted by He et al . (2011) used a mechanistic modeling approach to study the three waves of the 1918 influenza pandemic. They examined the factors that underlie variability in temporal patterns and their correlation to patterns of mortality and morbidity. Their analysis suggests that temporal variations in transmission rate provide the best explanation, and the variation in transmission required to generate these three waves is within biologically plausible values. Another study by He et al . (2013) used a simple epidemic model incorporating three factors to infer the cause of the three waves of the 1918 influenza pandemic. These factors were school opening and closing, temperature changes throughout the outbreak, and human behavioral changes in response to the outbreak. Their modeling results showed that all three factors are important, but human behavioral responses showed the most significant effects. Academic Andrew Price-Smith has made the argument that the virus helped tip the balance of power in the latter days of the war towards the Allied cause. He provides data that the viral waves hit the Central Powers before the Allied powers and that both morbidity and mortality in Germany and Austria were considerably higher than in Britain and France. A 2006 Lancet study corroborates higher excess mortality rates in Germany (0.76%) and Austria (1.61%) compared to Britain (0.34%) and France (0.75%). Kenneth Kahn at Oxford University Computing Services writes that "Many researchers have suggested that the conditions of the war significantly aided the spread of the disease. And others have argued that the course of the war (and subsequent peace treaty) was influenced by the pandemic." Kahn has developed a model that can be used on home computers to test these theories. Many businesses in the entertainment and service industries suffered losses in revenue, while the healthcare industry reported profit gains. Historian Nancy Bristow has argued that the pandemic, when combined with the increasing number of women attending college, contributed to the success of women in the field of nursing. This was due in part to the failure of medical doctors, who were predominantly men, to contain and prevent the illness. Nursing staff, who were mainly women, celebrated the success of their patient care and did not associate the spread of the disease with their work. A 2020 study found that U.S. cities that implemented early and extensive non-medical measures (quarantine, etc.) suffered no additional adverse economic effects due to implementing those measures. However, the validity of this study has been questioned because of the coincidence of WWI and other problems with data reliability. A 2006 study in the Journal of Political Economy found that "cohorts in utero during the pandemic displayed reduced educational attainment, increased rates of physical disability, lower income, lower socioeconomic status, and higher transfer payments received compared with other birth cohorts." A 2018 study found that the pandemic reduced educational attainment in populations. The flu has also been linked to the outbreak of encephalitis lethargica in the 1920s. Survivors faced an elevated mortality risk. Some survivors did not fully recover from physiological conditions resulting from infection. Academic Andrew Price-Smith has made the argument that the virus helped tip the balance of power in the latter days of the war towards the Allied cause. He provides data that the viral waves hit the Central Powers before the Allied powers and that both morbidity and mortality in Germany and Austria were considerably higher than in Britain and France. A 2006 Lancet study corroborates higher excess mortality rates in Germany (0.76%) and Austria (1.61%) compared to Britain (0.34%) and France (0.75%). Kenneth Kahn at Oxford University Computing Services writes that "Many researchers have suggested that the conditions of the war significantly aided the spread of the disease. And others have argued that the course of the war (and subsequent peace treaty) was influenced by the pandemic." Kahn has developed a model that can be used on home computers to test these theories. Many businesses in the entertainment and service industries suffered losses in revenue, while the healthcare industry reported profit gains. Historian Nancy Bristow has argued that the pandemic, when combined with the increasing number of women attending college, contributed to the success of women in the field of nursing. This was due in part to the failure of medical doctors, who were predominantly men, to contain and prevent the illness. Nursing staff, who were mainly women, celebrated the success of their patient care and did not associate the spread of the disease with their work. A 2020 study found that U.S. cities that implemented early and extensive non-medical measures (quarantine, etc.) suffered no additional adverse economic effects due to implementing those measures. However, the validity of this study has been questioned because of the coincidence of WWI and other problems with data reliability. A 2006 study in the Journal of Political Economy found that "cohorts in utero during the pandemic displayed reduced educational attainment, increased rates of physical disability, lower income, lower socioeconomic status, and higher transfer payments received compared with other birth cohorts." A 2018 study found that the pandemic reduced educational attainment in populations. The flu has also been linked to the outbreak of encephalitis lethargica in the 1920s. Survivors faced an elevated mortality risk. Some survivors did not fully recover from physiological conditions resulting from infection. Despite the high morbidity and mortality rates that resulted from the epidemic, the Spanish flu began to fade from public awareness over the decades until the arrival of news about bird flu and other pandemics in the 1990s and 2000s. This has led some historians to label the Spanish flu a "forgotten pandemic". However, this label has been challenged by the historian Guy Beiner , who has charted a complex history of social and cultural forgetting, demonstrating how the pandemic was overshadowed by the commemoration of the First World War and mostly neglected in mainstream historiography, yet was remembered in private and local traditions across the globe. There are various theories of why the Spanish flu was "forgotten". The rapid pace of the pandemic, which killed most of its victims in the United States within less than nine months, resulted in limited media coverage. The general population was familiar with patterns of pandemic disease in the late 19th and early 20th centuries: typhoid, yellow fever , diphtheria , and cholera all occurred near the same time. These outbreaks probably lessened the significance of the influenza pandemic for the public. In some areas, the flu was not reported on, the only mention being that of advertisements for medicines claiming to cure it. Additionally, the outbreak coincided with the deaths and media focus on the First World War. Another explanation involves the age group affected by the disease. The majority of fatalities, from both the war and the epidemic, were among young adults. The high number of war-related deaths of young adults may have overshadowed the deaths caused by flu. When people read the obituaries, they saw the war or postwar deaths and the deaths from the influenza side by side. Particularly in Europe, where the war's toll was high, the flu may not have had a tremendous psychological impact or may have seemed an extension of the war's tragedies. The duration of the pandemic and the war could have also played a role. The war, however, had initially been expected to end quickly but lasted for four years by the time the pandemic struck. Despite the toll of the pandemic, it was never a large theme in American literature. Alfred Crosby suspects that it may be due to the fact that it occurred after World War I, which was the most important event in that generation's lives. Katherine Anne Porter 's 1939 novella Pale Horse, Pale Rider is one of the most well-known fictional accounts of the pandemic. The 2006 novel The Last Town on Earth focuses on a town which attempts to limit the spread of the flu by preventing people from entering or leaving. The Pull of the Stars is a 2020 novel by Emma Donoghue set in Dublin during the Spanish flu. Its final draft was submitted in March 2020, and publishers fast-tracked publication because of the then ongoing COVID-19 pandemic . The Spanish flu killed a much lower percentage of the world's population than the Black Death , which lasted for many more years. The recent COVID-19 pandemic is estimated to have killed 17.5 - 31.4 million. Despite the toll of the pandemic, it was never a large theme in American literature. Alfred Crosby suspects that it may be due to the fact that it occurred after World War I, which was the most important event in that generation's lives. Katherine Anne Porter 's 1939 novella Pale Horse, Pale Rider is one of the most well-known fictional accounts of the pandemic. The 2006 novel The Last Town on Earth focuses on a town which attempts to limit the spread of the flu by preventing people from entering or leaving. The Pull of the Stars is a 2020 novel by Emma Donoghue set in Dublin during the Spanish flu. Its final draft was submitted in March 2020, and publishers fast-tracked publication because of the then ongoing COVID-19 pandemic . The Spanish flu killed a much lower percentage of the world's population than the Black Death , which lasted for many more years. The recent COVID-19 pandemic is estimated to have killed 17.5 - 31.4 million. The origin of the Spanish flu pandemic, and the relationship between the near-simultaneous outbreaks in humans and swine, have been controversial. One hypothesis is that the virus strain originated at Fort Riley, Kansas, in viruses in poultry and swine which the fort bred for food; the soldiers were then sent from Fort Riley around the world, where they spread the disease. Similarities between a reconstruction of the virus and avian viruses, combined with the human pandemic preceding the first reports of influenza in swine, led researchers to conclude the influenza virus jumped directly from birds to humans, and swine caught the disease from humans. Others have disagreed, and more recent research has suggested the strain may have originated in a nonhuman, mammalian species. An estimated date for its appearance in mammalian hosts has been put at the period 1882–1913. This ancestor virus diverged about 1913–1915 into two clades (or biological groups each descended from a common ancestor), which gave rise to the classical swine and human H1N1 influenza lineages. The last common ancestor of human strains dates between February 1917 and April 1918. Because pigs are more readily infected with avian influenza viruses than are humans, they were suggested as the original recipients of the virus, passing the virus to humans sometime between 1913 and 1918. An effort to recreate the Spanish flu strain (a subtype of avian strain H1N1) was a collaboration among the Armed Forces Institute of Pathology , the USDA ARS Southeast Poultry Research Laboratory, and Mount Sinai School of Medicine in New York City. The effort resulted in the announcement (on 5 October 2005) that the group had successfully determined the virus' genetic sequence , using historic tissue samples recovered by pathologist Johan Hultin from an Inuit female flu victim buried in the Alaskan permafrost and samples preserved from American soldiers Roscoe Vaughan and James Downs. On 18 January 2007, Kobasa et al. (2007) reported that monkeys ( Macaca fascicularis ) infected with the recreated flu strain exhibited classic symptoms of the 1918 pandemic, and died from cytokine storms – an overreaction of the immune system. This may explain why the Spanish flu had its surprising effect on younger, healthier people, as a person with a stronger immune system would potentially have a stronger overreaction. On 16 September 2008, the body of British politician and diplomat Sir Mark Sykes was exhumed to study the RNA of the flu virus in efforts to understand the genetic structure of modern H5N1 bird flu. Sykes had been buried in 1919 in a lead coffin which scientists hoped had helped preserve the virus. The coffin was found to be split and the cadaver badly decomposed; nonetheless, samples of lung and brain tissue were taken. In December 2008, research by Yoshihiro Kawaoka of the University of Wisconsin linked the presence of three specific genes (termed PA, PB1, and PB2) and a nucleoprotein derived from Spanish flu samples to the ability of the flu virus to invade the lungs and cause pneumonia. The combination triggered similar symptoms in animal testing. In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the Spanish flu pandemic strain. One of the few things known for certain about influenza in 1918 and for some years after was that it was, except in the laboratory, exclusively a disease of human beings. In 2013, the AIR Worldwide Research and Modeling Group "characterized the historic 1918 pandemic and estimated the effects of a similar pandemic occurring today using the AIR Pandemic Flu Model". In the model, "a modern-day 'Spanish flu' event would result in additional life insurance losses of between US$15.3–27.8 billion in the United States alone", with 188,000–337,000 deaths in the United States. In 2018, Michael Worobey, an evolutionary biology professor at the University of Arizona who is examining the history of the 1918 pandemic, revealed that he obtained tissue slides created by William Rolland, a physician who reported on a respiratory illness likely to be the virus while a pathologist in the British military during World War One. Rolland had authored an article in the Lancet during 1917 about a respiratory illness outbreak beginning in 1916 in Étaples, France. Worobey traced recent references to that article to family members who had retained slides that Rolland had prepared during that time. Worobey extracted tissue from the slides to potentially reveal more about the origin of the pathogen. In 2021 an investigation used the virus sequence to obtain the Hemagglutinin (HA) antigen and observe the adaptive immunity in 32 survivors of the 1918 flu pandemic, all of them presented seroreactivity and 7 of 8 further tested presented memory B cells able to produce antibodies that bound to the HA antigen highlighting the ability of the immunological memory many decades after.The high mortality rate of the influenza pandemic is one aspect that sets the pandemic apart from other disease outbreaks. Another factor is the higher mortality rate of men compared with women. Men with an underlying condition were at significantly more risk. Tuberculosis was one of the deadliest diseases in the 1900s, and killed more men than women. But with the spread of influenza disease, the cases of tuberculosis cases in men decreased. Many scholars have noted that tuberculosis increased the mortality rate of influenza in males, decreasing their life expectancy. During the 1900s tuberculosis was more common in males than females, but studies show that when influenza spread the tuberculosis mortality rate among females changed. The death rate of tuberculosis in females increased significantly and would continue to decline until post-pandemic. Death rates were particularly high in those aged 20–35. The only comparable disease to this was the Black Death , or bubonic plague , in the 1300s. As other studies have shown, tuberculosis and influenza had comorbidities and one affected the other. The ages of males dying of the flu show that tuberculosis was a factor, and as males primarily had this disease at the time of the pandemic, they had a higher mortality rate. Life expectancy dropped in males during the pandemic but then increased two years after the pandemic. One major cause of the spread of influenza was social behavior. Men had more social variation and were mobile more than women due to their work. Even though there was a higher mortality rate in males, each region showed different results, due to such factors as nutritional deficiency . In Newfoundland , the pandemic spread was highly variable. Influenza did not discriminate who was infected, indeed it attacked the socioeconomic status of people. Although social variability allowed the disease to move quickly geographically, it tended to spread faster and affect men more than women due to labor and social contact. Newfoundland's leading cause of death before the pandemic was tuberculosis and this is known to be a severe underlying condition for people and increases the |mortality rate when infected by the influenza disease. There was diverse labor in Newfoundland, men and women had various occupations that involved day-to-day interaction. But, fishing had a major role in the economy and so males were more mobile than females and had more contact with other parts of the world. The spread of the pandemic is known to have begun in the spring of 1918, but Newfoundland did not see the deadly wave until June or July, which aligns with the high demand for employment in the fishery. The majority of men were working along the coast during the summer and it was typical for entire families to move to Newfoundland and work. Studies show a much higher mortality rate in males compared with females. But, during the first, second, and third waves of the pandemic, the mortality shifted. During the first wave, men had a higher mortality rate, but the mortality rate of females increased and was higher during the second and third waves. The female population was larger in certain regions of Newfoundland and therefore had a bigger impact on the death rate. Records indicate the most deaths during the first wave of the pandemic were among young men in their 20s, which reflects the age of enlistment in the war. The mobility of young men during 1918 was linked to the spread of influenza and the biggest wave of the epidemic. In late 1917 and throughout 1918, thousands of male troops gathered at the Halifax port before heading to Europe. Any soldier that was ill and could not depart was added to the population of Halifax , which increased the case rate of influenza among men during the war . To determine the cause of the death during the pandemic, war scientists used the Commonwealth War Graves Commission (CWGC), which reported under 2 million men and women died during the wars, with a record of those who died from 1917 to 1918. The movement of soldiers during this time and the transportation from United States between Canada likely had a significant effect on the spread of the pandemic. One major cause of the spread of influenza was social behavior. Men had more social variation and were mobile more than women due to their work. Even though there was a higher mortality rate in males, each region showed different results, due to such factors as nutritional deficiency . In Newfoundland , the pandemic spread was highly variable. Influenza did not discriminate who was infected, indeed it attacked the socioeconomic status of people. Although social variability allowed the disease to move quickly geographically, it tended to spread faster and affect men more than women due to labor and social contact. Newfoundland's leading cause of death before the pandemic was tuberculosis and this is known to be a severe underlying condition for people and increases the |mortality rate when infected by the influenza disease. There was diverse labor in Newfoundland, men and women had various occupations that involved day-to-day interaction. But, fishing had a major role in the economy and so males were more mobile than females and had more contact with other parts of the world. The spread of the pandemic is known to have begun in the spring of 1918, but Newfoundland did not see the deadly wave until June or July, which aligns with the high demand for employment in the fishery. The majority of men were working along the coast during the summer and it was typical for entire families to move to Newfoundland and work. Studies show a much higher mortality rate in males compared with females. But, during the first, second, and third waves of the pandemic, the mortality shifted. During the first wave, men had a higher mortality rate, but the mortality rate of females increased and was higher during the second and third waves. The female population was larger in certain regions of Newfoundland and therefore had a bigger impact on the death rate. Records indicate the most deaths during the first wave of the pandemic were among young men in their 20s, which reflects the age of enlistment in the war. The mobility of young men during 1918 was linked to the spread of influenza and the biggest wave of the epidemic. In late 1917 and throughout 1918, thousands of male troops gathered at the Halifax port before heading to Europe. Any soldier that was ill and could not depart was added to the population of Halifax , which increased the case rate of influenza among men during the war . To determine the cause of the death during the pandemic, war scientists used the Commonwealth War Graves Commission (CWGC), which reported under 2 million men and women died during the wars, with a record of those who died from 1917 to 1918. The movement of soldiers during this time and the transportation from United States between Canada likely had a significant effect on the spread of the pandemic. Records indicate the most deaths during the first wave of the pandemic were among young men in their 20s, which reflects the age of enlistment in the war. The mobility of young men during 1918 was linked to the spread of influenza and the biggest wave of the epidemic. In late 1917 and throughout 1918, thousands of male troops gathered at the Halifax port before heading to Europe. Any soldier that was ill and could not depart was added to the population of Halifax , which increased the case rate of influenza among men during the war . To determine the cause of the death during the pandemic, war scientists used the Commonwealth War Graves Commission (CWGC), which reported under 2 million men and women died during the wars, with a record of those who died from 1917 to 1918. The movement of soldiers during this time and the transportation from United States between Canada likely had a significant effect on the spread of the pandemic.

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Pandemic influenza

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2009 swine flu pandemic

The 2009 swine flu pandemic , caused by the H1N1/swine flu/influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, was the third recent flu pandemic involving the H1N1 virus (the first being the 1918–1920 Spanish flu pandemic and the second being the 1977 Russian flu ). The first identified human case was in La Gloria , Mexico, a rural town in Veracruz. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term " swine flu ". Some studies estimated that the real number of cases including asymptomatic and mild cases could be 700 million to 1.4 billion people—or 11 to 21 percent of the global population of 6.8 billion at the time. The lower value of 700 million is more than the 500 million people estimated to have been infected by the Spanish flu pandemic. However, the Spanish flu infected approximately a third of the world population at the time, a much higher proportion. The number of lab-confirmed deaths reported to the WHO is 18,449 and is widely considered a gross underestimate. The WHO collaborated with the US Centers for Disease Control and Prevention (USCDC) and Netherlands Institute for Health Services Research (NIVEL) to produce two independent estimates of the influenza deaths that occurred during the global pandemic using two distinct methodologies. The 2009 H1N1 flu pandemic is estimated to have actually caused about 284,000 (range from 150,000 to 575,000) excess deaths by the WHO-USCDC study and 148,000–249,000 excess respiratory deaths by the WHO-NIVEL study. A study done in September 2010 showed that the risk of serious illness resulting from the 2009 H1N1 flu was no higher than that of the yearly seasonal flu . For comparison, the WHO estimates that 250,000 to 500,000 people die of seasonal flu annually. However, the H1N1 influenza epidemic in 2009 resulted in a large increase in the number of new cases of narcolepsy . Unlike most strains of influenza, the pandemic H1N1/09 virus did not disproportionately infect adults older than 60 years; this was an unusual and characteristic feature of the H1N1 pandemic . Even in the case of previously healthy people, a small percentage develop pneumonia or acute respiratory distress syndrome (ARDS). This manifests itself as increased breathing difficulty and typically occurs three to six days after initial onset of flu symptoms. The pneumonia caused by flu can be either direct viral pneumonia or a secondary bacterial pneumonia . A November 2009 New England Journal of Medicine article recommended that flu patients whose chest X-ray indicates pneumonia receive both antivirals and antibiotics . In particular, it is a warning sign if a child seems to be getting better and then relapses with high fever, as this relapse may be bacterial pneumonia. The World Health Organization uses the term "(H1N1) 2009 pandemic" when referring to the event, and officially adopted the name "A(H1N1)pdm09" for the virus in 2010, after the conclusion of the pandemic. Controversy arose early on regarding the wide assortment of terms used by journalists, academics, and officials. Labels like "H1N1 flu", "Swine flu", "Mexican flu", and variations thereof were typical. Criticism centered on how these names may confuse or mislead the public. It was argued that the names were overly technical (e.g. "H1N1"), incorrectly implying that the disease is caused by contact with pigs or pig products, or provoking stigmatization against certain communities (e.g. "Mexican"). Some academics of the time asserted there is nothing wrong with such names, while research published years later (in 2013) concluded that Mexican Americans and Latino Americans had indeed been stigmatized due to the frequent use of term "Mexican flu" in the news media. Official entities adopted terms with varying consistency over the course of the pandemic. The CDC used names like "novel influenza A (H1N1)" or "2009 H1N1 flu". The Netherlands National Institute for Public Health and the Environment used the term "Pig Flu" early on. Officials in Taiwan suggested use of the names "H1N1 flu" or "new flu". The World Organization for Animal Health , an IGO based in Europe, proposed the name "North American influenza". The European Commission adopted the term "novel flu virus". Officials in Israel and South Korea briefly considered adoption of the name "Mexican virus" due to concern about the use of the word "swine". In Israel, objections stemmed from sensitivity to religious restrictions on eating pork in the Jewish and Muslim populations, in South Korea , concerns were influenced by the importance of pork and domestic pigs . As terminology changed to deal with these and other such issues, further criticism was made that the situation was unnecessarily confusing. For example, the news department at the journal Science produced an article with the humorous title "Swine Flu Names Evolving Faster Than Swine Flu Itself". Analysis of the genetic divergence of the virus in samples from different cases indicated that the virus jumped to humans in 2008, probably after June, and not later than the end of November, likely around September 2008. The research also indicated the virus had been latent in pigs for several months prior to the outbreak, suggesting a need to increase agricultural surveillance to prevent future outbreaks. In 2009, U.S. agricultural officials speculated, although emphasizing that there was no way to prove their hypothesis, that "contrary to the popular assumption that the new swine flu pandemic arose on factory farms in Mexico, [the virus] most likely emerged in pigs in Asia, but then traveled to North America in a human." However, a subsequent report by researchers at the Mount Sinai School of Medicine in 2016 found that the 2009 H1N1 virus likely originated from pigs in a very small region of central Mexico. Initially called an "outbreak", widespread H1N1 infection was first recognized in the state of Veracruz , Mexico, with evidence that the virus had been present for months before it was officially called an "epidemic". The Mexican government closed most of Mexico City 's public and private facilities in an attempt to contain the spread of the virus; however, it continued to spread globally, and clinics in some areas were overwhelmed by infected people. The new virus was first isolated in late April by American and Canadian laboratories from samples taken from people with flu in Mexico, Southern California, and Texas. Soon the earliest known human case was traced to a case from 9 March 2009 in a 5-year-old boy in La Gloria, Mexico, a rural town in Veracruz. In late April, the World Health Organization (WHO) declared its first ever "public health emergency of international concern", or PHEIC , and in June, the WHO and the U.S. CDC stopped counting cases and declared the outbreak a pandemic . Despite being informally called "swine flu", the H1N1 flu virus cannot be spread by eating pork products; similar to other influenza viruses, it is typically contracted by person to person transmission through respiratory droplets. Symptoms usually last 4–6 days. Antivirals ( oseltamivir or zanamivir ) were recommended for those with more severe symptoms or those in an at-risk group. The pandemic began to taper off in November 2009, and by May 2010, the number of cases was in steep decline. On 10 August 2010, the Director-General of the WHO, Margaret Chan , announced the end of the H1N1 pandemic and announced that the H1N1 influenza event had moved into the post-pandemic period. According to WHO statistics (as of July 2010), the virus had killed more than 18,000 people since it appeared in April 2009; however, they state that the total mortality (including deaths unconfirmed or unreported) from the H1N1 strain is "unquestionably higher". Critics claimed the WHO had exaggerated the danger, spreading "fear and confusion" rather than "immediate information". The WHO began an investigation to determine whether it had "frightened people unnecessarily". A flu follow-up study done in September 2010, found that "the risk of most serious complications was not elevated in adults or children." In a 5 August 2011 PLOS ONE article, researchers estimated that the 2009 H1N1 global infection rate was 11% to 21%, lower than what was previously expected. However, by 2012, research showed that as many as 579,000 people could have been killed by the disease, as only those fatalities confirmed by laboratory testing were included in the original number, and meant that many without access to health facilities went uncounted. The majority of these deaths occurred in Africa and Southeast Asia. Experts, including the WHO, have agreed that an estimated 284,500 people were killed by the disease, much higher than the initial death toll. The symptoms of H1N1 flu are similar to those of other influenzas , and may include fever, cough (typically a "dry cough"), headache, dizziness, sneezing, muscle or joint pain, sore throat , chills , fatigue , and runny nose . Diarrhea , vomiting, and neurological problems have also been reported in some cases. People at higher risk of serious complications include people over 65, children younger than 5, children with neurodevelopmental conditions , pregnant women (especially during the third trimester), and people of any age with underlying medical conditions, such as asthma, diabetes, obesity, heart disease, or a weakened immune system (e.g., taking immunosuppressive medications or infected with HIV). More than 70% of hospitalizations in the U.S. have been people with such underlying conditions, according to the CDC . In September 2009, the CDC reported that the H1N1 flu "seems to be taking a heavier toll among chronically ill children than the seasonal flu usually does". Through 8 August 2009, the CDC had received 36 reports of pediatric deaths with associated influenza symptoms and laboratory-confirmed pandemic H1N1 from state and local health authorities within the United States, with 22 of these children having neurodevelopmental conditions such as cerebral palsy , muscular dystrophy , or developmental delays . "Children with nerve and muscle problems may be at especially high risk for complications because they cannot cough hard enough to clear their airways". From 26 April 2009, to 13 February 2010, the CDC had received reports of the deaths of 277 children with laboratory-confirmed 2009 influenza A (H1N1) within the United States. The World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit . Upon admission, most patients need immediate respiratory support with mechanical ventilation . Most complications have occurred among previously unhealthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation . Secondary bacterial infection is more common in children. Staphylococcus aureus , including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate; Streptococcus pneumoniae is the second most important cause of secondary bacterial pneumonia for children and primary for adults. Neuromuscular and cardiac complications are unusual but may occur. A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma , and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia , but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥ 100 mg/L) . 59% of all in-hospital deaths occurred in previously healthy people. Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died. Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism . In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli. An article published in JAMA in September 2010 challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. The World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit . Upon admission, most patients need immediate respiratory support with mechanical ventilation . Most complications have occurred among previously unhealthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation . Secondary bacterial infection is more common in children. Staphylococcus aureus , including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate; Streptococcus pneumoniae is the second most important cause of secondary bacterial pneumonia for children and primary for adults. Neuromuscular and cardiac complications are unusual but may occur. A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma , and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia , but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥ 100 mg/L) . 59% of all in-hospital deaths occurred in previously healthy people. Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died. Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism . In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli. An article published in JAMA in September 2010 challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. Confirmed diagnosis of pandemic H1N1 flu requires testing of a nasopharyngeal , nasal, or oropharyngeal tissue swab from the patient. Real-time RT-PCR is the recommended test as others are unable to differentiate between pandemic H1N1 and regular seasonal flu . However, most people with flu symptoms do not need a test for pandemic H1N1 flu specifically, because the test results usually do not affect the recommended course of treatment. The U.S. CDC recommend testing only for people who are hospitalized with suspected flu, pregnant women, and people with weakened immune systems. For the mere diagnosis of influenza and not pandemic H1N1 flu specifically, more widely available tests include rapid influenza diagnostic tests (RIDT), which yield results in about 30 minutes, and direct and indirect immunofluorescence assays ( DFA and IFA), which take 2–4 hours. Due to the high rate of RIDT false negatives , the CDC advises that patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications, and if a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. The use of RIDTs has been questioned by researcher Paul Schreckenberger of the Loyola University Health System, who suggests that rapid tests may actually pose a dangerous public health risk. Nikki Shindo of the WHO has expressed regret at reports of treatment being delayed by waiting for H1N1 test results and suggests, "[D]octors should not wait for the laboratory confirmation but make diagnosis based on clinical and epidemiological backgrounds and start treatment early." On 22 June 2010, the CDC announced a new test called the "CDC Influenza 2009 A (H1N1)pdm Real-Time RT-PCR Panel (IVD)". It uses a molecular biology technique to detect influenza A viruses and specifically the 2009 H1N1 virus. The new test will replace the previous real-time RT-PCR diagnostic test used during the 2009 H1N1 pandemic, which received an emergency use authorization from the U.S. Food and Drug Administration in April 2009. Tests results are available in four hours and are 96% accurate. The virus was found to be a novel strain of influenza for which existing vaccines against seasonal flu provided little protection. A study at the U.S. Centers for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain but that adults, particularly those older than 60, had some degree of immunity . Children showed no cross-reactive antibody reaction to the new strain, adults aged 18 to 60 had 6–9%, and older adults 33%. While it has been thought that these findings suggest the partial immunity in older adults may be due to previous exposure to similar seasonal influenza viruses, a November 2009 study of a rural unvaccinated population in China found only a 0.3% cross-reactive antibody reaction to the H1N1 strain, suggesting that previous vaccinations for seasonal flu and not exposure may have resulted in the immunity found in the older U.S. population. Analyses of the genetic sequences of the first isolates, promptly shared on the GISAID database according to Nature and WHO, soon determined that the strain contains genes from five different flu viruses: North American swine influenza, North American avian influenza, human influenza, and two swine influenza viruses typically found in Asia and Europe. Further analysis has shown that several proteins of the virus are most similar to strains that cause mild symptoms in humans, leading virologist Wendy Barclay to suggest on 1 May 2009, that the initial indications are that the virus was unlikely to cause severe symptoms for most people. The virus was less lethal than previous pandemic strains and killed about 0.01–0.03% of those infected; the 1918 influenza was about one hundred times more lethal and had a case fatality rate of 2–3%. By 14 November 2009, the virus had infected one in six Americans with 200,000 hospitalisations and 10,000 deaths—as many hospitalizations and fewer deaths than in an average flu season overall, but with much higher risk for those under 50. With deaths of 1,100 children and 7,500 adults 18 to 64, these figures were deemed "much higher than in a usual flu season" during the pandemic. In June 2010, scientists from Hong Kong reported discovery of a new swine flu virus: a hybrid of the pandemic H1N1 virus and viruses previously found in pigs. It was the first report of a reassortment of the pandemic virus, which in humans had been slow to evolve. Nancy Cox , head of the influenza division at the U.S. Centers for Disease Control and Prevention, has said, "This particular paper is extremely interesting because it demonstrates for the first time what we had worried about at the very onset of the pandemic, and that is that this particular virus, when introduced into pigs, could reassort with the resident viruses in pigs and we would have new gene constellations. And bingo, here we are." Pigs have been termed the mixing vessel of flu because they can be infected both by avian flu viruses, which rarely directly infect people, and by human viruses. When pigs become simultaneously infected with more than one virus, the viruses can swap genes, producing new variants which can pass to humans and sometimes spread amongst them. "Unlike the situation with birds and humans, we have a situation with pigs and humans where there's a two-way street of exchange of viruses. With pigs it's very much a two-way street." Spread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something—such as a surface or object—with flu viruses on it and then touching their face. The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75. A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms. The H1N1 virus has been transmitted to animals, including swine , turkeys , ferrets , household cats, at least one dog, and a cheetah . Spread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something—such as a surface or object—with flu viruses on it and then touching their face. The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75. A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms. The H1N1 virus has been transmitted to animals, including swine , turkeys , ferrets , household cats, at least one dog, and a cheetah . Because the H1N1 vaccine was initially in short supply in the U.S., the CDC recommended that initial doses should go to priority groups such as pregnant women, people who live with or care for babies under six months old, children six months to four years old and health-care workers. In the UK, the NHS recommended vaccine priority go to people over six months old who were clinically at risk for seasonal flu, pregnant women and households of people with compromised immunity. Although it was initially thought that two injections would be required, clinical trials showed that the new vaccine protected adults "with only one dose instead of two;" thus the limited vaccine supplies would go twice as far as had been predicted. Health officials worldwide were also concerned because the virus was new and could easily mutate and become more virulent, even though most flu symptoms were mild and lasted only a few days without treatment. Officials also urged communities, businesses, and individuals to make contingency plans for possible school closures, multiple employee absences for illness, surges of patients in hospitals, and other effects of potentially widespread outbreaks. Disaster response organizations such as Direct Relief helped by providing protective items to clinical workers to help them stay healthy throughout flu season. In February 2010, the CDC's Advisory Committee on Immunization Practices voted for "universal" flu vaccination in the U.S. to include all people over six months of age. The 2010–2011 vaccine will protect against the 2009 H1N1 pandemic virus and two other flu viruses. On 27 April 2009, the European Union health commissioner advised Europeans to postpone nonessential travel to the United States or Mexico. This followed the discovery of the first confirmed case in Spain. On 6 May 2009, the Public Health Agency of Canada announced that their National Microbiology Laboratory (NML) had mapped the genetic code of the swine flu virus, the first time that had been done. In the U.K., the National Health Service launched a website, the National Pandemic Flu Service, allowing patients to self-assess and get an authorisation number for antiviral medication. The system was expected to reduce the burden on general practitioners . U.S. officials observed that six years of concern about H5N1 avian flu did much to prepare for the current H1N1 outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected over the years, many countries took steps to try to prevent any similar crisis from spreading further. The CDC and other U.S. governmental agencies used the summer lull to take stock of the United States response to H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn. Preparations included planning a second influenza vaccination program in addition to the one for seasonal flu, and improving coordination between federal, state, and local governments and private health providers. On 24 October 2009, U.S. President Obama declared swine flu a national emergency, giving Secretary of Health and Human Services Kathleen Sebelius authority to grant waivers to requesting hospitals from usual federal requirements. By 19 November 2009, doses of vaccine had been administered in over 16 countries. A 2009 review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 vaccine has a safety profile similar to that of the seasonal vaccine. In 2011, a study from the US Flu Vaccine Effectiveness Network estimated the overall effectiveness of all pandemic H1N1 vaccines at 56%. A CDC study released 28 January 2013, estimated that the Pandemic H1N1 vaccine saved roughly 300 lives and prevented about a million illnesses in the US. The study concluded that had the vaccination program started two weeks earlier, close to 60% more cases could have been prevented. The study was based on an effectiveness in preventing cases, hospitalizations, and deaths of 62% for all subgroups except people over 65, for whom the effectiveness was estimated at 43%. The effectiveness was based on European and Asian studies and expert opinion. The delay in vaccine administration demonstrated the shortcomings of the world's capacity for vaccine-production, as well as problems with international distribution. Some manufacturers and wealthy countries had concerns regarding liability and regulations, as well as the logistics of transporting, storing, and administering vaccines to be donated to poorer countries. In January 2010, Wolfgang Wodarg , a German deputy who trained as a physician and chaired the health committee at the Council of Europe , claimed that major firms had organized a "campaign of panic" to put pressure on the World Health Organization (WHO) to declare a "false pandemic" to sell vaccines. Wodarg said the WHO's "false pandemic" flu campaign is "one of the greatest medicine scandals of the century". He said that the "false pandemic" campaign began in May 2009 in Mexico City , when a hundred or so "normal" reported influenza cases were declared to be the beginning of a threatening new pandemic, although he said there was little scientific evidence for it. Nevertheless, he argued that the WHO, "in cooperation with some big pharmaceutical companies and their scientists, re-defined pandemics," removing the statement that "an enormous amount of people have contracted the illness or died" from its existing definition and replacing it by stating simply that there has to be a virus, spreading beyond borders and to which people have no immunity. The WHO responded by stating that they take their duty to provide independent advice seriously and guarded against interference from outside interests. Announcing a review of the WHO's actions, spokeswoman Fadela Chaib stated: "Criticism is part of an outbreak cycle. We expect and indeed welcome criticism and the chance to discuss it". The WHO also stated on their website that "The world is going through a real pandemic. The description of it as a fake is wrong and irresponsible". In March 2010, the Council of Europe launched an enquiry into "the influence of the pharmaceutical companies on the global swine flu campaign", and a preliminary report was in preparation. On 12 April 2010, Keiji Fukuda, the WHO's top influenza expert, stated that the system leading to the declaration of a pandemic led to confusion about H1N1 circulating around the world and he expressed concern that there was a failure to communicate in regard to uncertainties about the new virus, which turned out to be not as deadly as feared. WHO Director-General Margaret Chan appointed 29 flu experts from outside the organization to conduct a review of WHO's handling of the H1N1 flu pandemic. She told them, "We want a frank, critical, transparent, credible and independent review of our performance." In June 2010, Fiona Godlee , editor-in-chief of the BMJ , published an editorial which criticised the WHO, saying that an investigation had disclosed that some of the experts advising WHO on the pandemic had financial ties with drug companies which were producing antivirals and vaccines. Margaret Chan, Director-General of the WHO, replied stating, "Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry. The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive". On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. On 27 April 2009, the European Union health commissioner advised Europeans to postpone nonessential travel to the United States or Mexico. This followed the discovery of the first confirmed case in Spain. On 6 May 2009, the Public Health Agency of Canada announced that their National Microbiology Laboratory (NML) had mapped the genetic code of the swine flu virus, the first time that had been done. In the U.K., the National Health Service launched a website, the National Pandemic Flu Service, allowing patients to self-assess and get an authorisation number for antiviral medication. The system was expected to reduce the burden on general practitioners . U.S. officials observed that six years of concern about H5N1 avian flu did much to prepare for the current H1N1 outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected over the years, many countries took steps to try to prevent any similar crisis from spreading further. The CDC and other U.S. governmental agencies used the summer lull to take stock of the United States response to H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn. Preparations included planning a second influenza vaccination program in addition to the one for seasonal flu, and improving coordination between federal, state, and local governments and private health providers. On 24 October 2009, U.S. President Obama declared swine flu a national emergency, giving Secretary of Health and Human Services Kathleen Sebelius authority to grant waivers to requesting hospitals from usual federal requirements. By 19 November 2009, doses of vaccine had been administered in over 16 countries. A 2009 review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 vaccine has a safety profile similar to that of the seasonal vaccine. In 2011, a study from the US Flu Vaccine Effectiveness Network estimated the overall effectiveness of all pandemic H1N1 vaccines at 56%. A CDC study released 28 January 2013, estimated that the Pandemic H1N1 vaccine saved roughly 300 lives and prevented about a million illnesses in the US. The study concluded that had the vaccination program started two weeks earlier, close to 60% more cases could have been prevented. The study was based on an effectiveness in preventing cases, hospitalizations, and deaths of 62% for all subgroups except people over 65, for whom the effectiveness was estimated at 43%. The effectiveness was based on European and Asian studies and expert opinion. The delay in vaccine administration demonstrated the shortcomings of the world's capacity for vaccine-production, as well as problems with international distribution. Some manufacturers and wealthy countries had concerns regarding liability and regulations, as well as the logistics of transporting, storing, and administering vaccines to be donated to poorer countries. In January 2010, Wolfgang Wodarg , a German deputy who trained as a physician and chaired the health committee at the Council of Europe , claimed that major firms had organized a "campaign of panic" to put pressure on the World Health Organization (WHO) to declare a "false pandemic" to sell vaccines. Wodarg said the WHO's "false pandemic" flu campaign is "one of the greatest medicine scandals of the century". He said that the "false pandemic" campaign began in May 2009 in Mexico City , when a hundred or so "normal" reported influenza cases were declared to be the beginning of a threatening new pandemic, although he said there was little scientific evidence for it. Nevertheless, he argued that the WHO, "in cooperation with some big pharmaceutical companies and their scientists, re-defined pandemics," removing the statement that "an enormous amount of people have contracted the illness or died" from its existing definition and replacing it by stating simply that there has to be a virus, spreading beyond borders and to which people have no immunity. The WHO responded by stating that they take their duty to provide independent advice seriously and guarded against interference from outside interests. Announcing a review of the WHO's actions, spokeswoman Fadela Chaib stated: "Criticism is part of an outbreak cycle. We expect and indeed welcome criticism and the chance to discuss it". The WHO also stated on their website that "The world is going through a real pandemic. The description of it as a fake is wrong and irresponsible". In March 2010, the Council of Europe launched an enquiry into "the influence of the pharmaceutical companies on the global swine flu campaign", and a preliminary report was in preparation. On 12 April 2010, Keiji Fukuda, the WHO's top influenza expert, stated that the system leading to the declaration of a pandemic led to confusion about H1N1 circulating around the world and he expressed concern that there was a failure to communicate in regard to uncertainties about the new virus, which turned out to be not as deadly as feared. WHO Director-General Margaret Chan appointed 29 flu experts from outside the organization to conduct a review of WHO's handling of the H1N1 flu pandemic. She told them, "We want a frank, critical, transparent, credible and independent review of our performance." In June 2010, Fiona Godlee , editor-in-chief of the BMJ , published an editorial which criticised the WHO, saying that an investigation had disclosed that some of the experts advising WHO on the pandemic had financial ties with drug companies which were producing antivirals and vaccines. Margaret Chan, Director-General of the WHO, replied stating, "Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry. The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive". On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel. On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-U.S. airlines, mostly Asian, including Singapore Airlines , China Eastern Airlines , China Southern Airlines , Cathay Pacific and Aeromexico , took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. U.S. government officials were especially concerned about schools because the H1N1 flu virus appeared to disproportionately affect young and school-age people, between six months and 24 years of age. The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer. The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill; schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks. In California, school districts and universities were on alert and worked with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools closed. University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department , parents, and school administrators. By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states. Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains . The CDC estimated that as much as 40% of the workforce might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advised that individuals should have steps in place should a workplace close down or a situation arise that requires remote work . The CDC further advised that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers. The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu. There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions. Yukihiro Nishiyama, professor of virology at Nagoya University 's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps". According to mask manufacturer 3M , masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus". However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia. They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease. During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present. Japan quarantined 47 airline passengers in a hotel for a week in mid-May, then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection. The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board , the American Meat Institute , and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009. The virus has been found in U.S. hogs, and Canadian as well as in hogs in Northern Ireland, Argentina, and Norway. Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu. Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas . The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April. A number of methods have been recommended to help ease symptoms, including adequate liquid intake and rest. Over-the-counter pain medications such as paracetamol and ibuprofen do not kill the virus; however, they may be useful to reduce symptoms. Aspirin and other salicylate products should not be used by people under 16 with any flu-type symptoms because of the risk of developing Reye's Syndrome . If the fever is mild and there are no other complications, fever medication is not recommended. Most people recover without medical attention, although ones with pre-existing or underlying medical conditions are more prone to complications and may benefit from further treatments. People in at-risk groups should be treated with antivirals (oseltamivir or zanamivir) as soon as possible when they first experience flu symptoms. The at-risk groups include pregnant and post partum women, children under two years old, and people with underlying conditions such as respiratory problems. People who are not in an at-risk group who have persistent or rapidly worsening symptoms should also be treated with antivirals. People who have developed pneumonia should be given both antivirals and antibiotics, as in many severe cases of H1N1-caused illness, bacterial infection develops. Antivirals are most useful if given within 48 hours of the start of symptoms and may improve outcomes in hospitalised patients. In those beyond 48 hours who are moderately or severely ill, antivirals may still be beneficial. If oseltamivir (Tamiflu) is unavailable or cannot be used, zanamivir (Relenza) is recommended as a substitute. Peramivir is an experimental antiviral drug approved for hospitalised patients in cases where the other available methods of treatment are ineffective or unavailable. To help avoid shortages of these drugs, the U.S. CDC recommended oseltamivir treatment primarily for people hospitalised with pandemic flu; people at risk of serious flu complications due to underlying medical conditions; and patients at risk of serious flu complications. The CDC warned that the indiscriminate use of antiviral medications to prevent and treat influenza could ease the way for drug-resistant strains to emerge, which would make the fight against the pandemic that much harder. In addition, a British report found that people often failed to complete a full course of the drug or took the medication when not needed. Both medications mentioned above for treatment, oseltamivir and zanamivir, have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite, and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir. The WHO warned against buying antiviral medications from online sources and estimated that half the drugs sold by online pharmacies without a physical address were counterfeit. In December 2012, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir ( Tamiflu ). It is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir. No circulating flu has yet shown any resistance to zanamivir ( Relenza ), the other available anti-viral. On 8 December 2009, the Cochrane Collaboration , which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza. Of note, their published finding related only to use in healthy adults with influenza but not in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults still left it as a useful drug for reducing the duration of symptoms. In general, the Cochrane Collaboration concluded "Paucity of good data". Both medications mentioned above for treatment, oseltamivir and zanamivir, have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite, and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir. The WHO warned against buying antiviral medications from online sources and estimated that half the drugs sold by online pharmacies without a physical address were counterfeit. In December 2012, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir ( Tamiflu ). It is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir. No circulating flu has yet shown any resistance to zanamivir ( Relenza ), the other available anti-viral. On 8 December 2009, the Cochrane Collaboration , which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza. Of note, their published finding related only to use in healthy adults with influenza but not in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults still left it as a useful drug for reducing the duration of symptoms. In general, the Cochrane Collaboration concluded "Paucity of good data". Note: The ratio of confirmed deaths to total deaths due to the pandemic is unknown. For more information, see " Data reporting and accuracy ". While it is not known precisely where or when the virus originated, analyses in scientific journals have suggested that the H1N1 strain responsible for the 2009 outbreak first evolved in September 2008 and circulated amongst humans for several months, before being formally recognised and identified as a novel strain of influenza. The virus was first reported in two U.S. children in March 2009, but health officials have reported that it apparently infected people as early as January 2009 in Mexico. The outbreak was first identified in Mexico City on 18 March 2009; immediately after the outbreak was officially announced, Mexico notified the U.S. and World Health Organization, and within days of the outbreak Mexico City was "effectively shut down". Some countries cancelled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected. Mexico already had hundreds of non-lethal cases before the outbreak was officially discovered, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases which showed more severe signs different from those of normal flu, possibly leading to a skewed initial estimate of the case fatality rate. The new strain was first identified by the CDC in two children, neither of whom had been in contact with pigs. The first case, from San Diego County, California , was confirmed from clinical specimens ( nasopharyngeal swab ) examined by the CDC on 14 April 2009. A second case, from nearby Imperial County, California , was confirmed on 17 April. The patient in the first confirmed case had flu symptoms including fever and cough upon clinical examination on 30 March and the second on 28 March. The first confirmed H1N1/09 pandemic flu death, which occurred at Texas Children's Hospital in Houston, Texas, was of a toddler from Mexico City who was visiting family in Brownsville, Texas , before being air-lifted to Houston for treatment. The Infectious Diseases Society of America estimated that the total number of deaths in the U.S. was 12,469. Influenza surveillance information "answers the questions of where, when, and what influenza viruses are circulating. Sharing of such information is especially crucial during an emergent pandemic as in April 2009, when the genetic sequences of the initial viruses were rapidly and openly shared via the GISAID Initiative within days of identification, playing a key role in facilitating an early response to the evolving pandemic. Surveillance is used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza." For example, as of late June, influenza surveillance information showed the U.S. had nearly 28,000 laboratory-confirmed cases including 3,065 hospitalizations and 127 deaths. But mathematical modelling showed an estimated 1 million Americans had the 2009 pandemic flu at the time, according to Lyn Finelli , a flu surveillance official with the CDC. Estimating deaths from influenza is also a complicated process. In 2005, influenza only appeared on the death certificates of 1,812 people in the US. The average annual US death toll from flu is, however, estimated to be 36,000. The CDC explains: "[I]nfluenza is infrequently listed on death certificates of people who die from flu-related complications" and hence, "Only counting deaths where influenza was included on a death certificate would be a gross underestimation of influenza's true impact." Influenza surveillance information on the 2009 H1N1 flu pandemic is available, but almost no studies attempted to estimate the total number of deaths attributable to H1N1 flu. Two studies were carried out by the CDC; the later of them estimated that between 7,070 and 13,930 deaths were attributable to H1N1 flu from April to 14 November 2009. During the same period, 1,642 deaths were officially confirmed as caused by H1N1 flu. The WHO stated in 2010 that total mortality (including unconfirmed or unreported deaths) from H1N1 flu was "unquestionably higher" than their own confirmed death statistics. The initial outbreak received a week of near-constant media attention. Epidemiologists cautioned that the number of cases reported in the early days of an outbreak can be very inaccurate and deceptive, due to several causes, among them selection bias , media bias and incorrect reporting by governments. Inaccuracies could also be caused by authorities in different countries looking at differing population groups. Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases. "[E]ven in developed countries the [numbers of flu deaths] are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness". Joseph S. Bresee, then CDC flu division's epidemiology chief and Michael Osterholm , director of the Center for Infectious Disease Research and Policy pointed out that millions of people have had H1N1 flu, usually in a mild form, so the numbers of laboratory-confirmed cases were actually meaningless, and in July 2009, the WHO stopped keeping count of individual cases and focused more on major outbreaks. A Wisconsin study published in the Journal of the American Medical Association in September 2010, reported that findings showed that the 2009 H1N1 flu was no more severe than the seasonal flu. "The risk of most serious complications was not elevated in adults or children", the study's authors wrote. "Children were disproportionately affected by 2009 H1N1 infection, but the perceived severity of symptoms and risk of serious outcomes were not increased." Children infected in the 2009 H1N1 flu pandemic were no more likely to be hospitalized with complications or get pneumonia than those who catch seasonal strains. About 1.5% of children with the H1N1 swine flu strain were hospitalized within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. CDC illness and death estimates from April 2009 to April 2010, in the US are as follows: It has been stated that about 36,000 die from the seasonal flu in the U.S. each year, and this is frequently understood as an indication that the H1N1 strain was not as severe as seasonal influenza. The 36,000 estimate was presented in a 2003 study by CDC scientists and refers to a period from 1990 to 1991 through 1998–99. During those years, the number of estimated deaths ranged from 17,000 to 52,000, with an average of about 36,000. Throughout that decade, influenza A (H3N2) was the predominant virus during most of the seasons, and H3N2 influenza viruses are typically associated with higher death rates. The JAMA study also looked at seasonal influenza-associated deaths over a 23-year period, from 1976 to 1977 and 1998–99 with estimates of respiratory and circulatory influenza-associated deaths ranging from about 5,000 to about 52,000, and an average of about 25,000. CDC believes that the range of deaths over the past 31 years (~3,000 to ~49,000) is a more accurate representation of the unpredictability and variability of flu-associated deaths. The annual toll from seasonal influenza in the US between 1979 and 2001 is estimated at 41,400 deaths on average. Therefore, the H1N1 pandemic estimated mortality of 8,870 to 18,300 is just below the mid-range of estimates. The 2009 pandemic caused US hospitals to make significant preparations in terms of hospital surge capacities, especially within the emergency department and among vulnerable populations. In many cases, hospitals were relatively successful in making sure that those patients most severely affected by the influenza strain were able to be seen, treated, and discharged in an efficient manner. A case-study of the preparation, planning, mitigation, and response efforts during the fall of 2009 is that of the Children's Hospital of Philadelphia (CHOP) which took several steps to increase the emergency department (ED) surge capacity response. CHOP used portions of the main lobby area as an ED waiting room; several of the region's hospital-based outpatient facilities were in use during evening and weekend hours for non-emergency cases; the ED's 24-hour short-stay unit was utilized to care for ED patients in a longer-term capacity; non-board certified physicians (in pediatric emergency medicine) and inpatient-unit medical nurses were utilized for ED patient care; hospital units normally utilized for other medical or therapeutic purposes were transformed into ED patient rooms; and rooms normally used for only one patient were expanded to at least a capacity of 2. The virus was first reported in two U.S. children in March 2009, but health officials have reported that it apparently infected people as early as January 2009 in Mexico. The outbreak was first identified in Mexico City on 18 March 2009; immediately after the outbreak was officially announced, Mexico notified the U.S. and World Health Organization, and within days of the outbreak Mexico City was "effectively shut down". Some countries cancelled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected. Mexico already had hundreds of non-lethal cases before the outbreak was officially discovered, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases which showed more severe signs different from those of normal flu, possibly leading to a skewed initial estimate of the case fatality rate. The new strain was first identified by the CDC in two children, neither of whom had been in contact with pigs. The first case, from San Diego County, California , was confirmed from clinical specimens ( nasopharyngeal swab ) examined by the CDC on 14 April 2009. A second case, from nearby Imperial County, California , was confirmed on 17 April. The patient in the first confirmed case had flu symptoms including fever and cough upon clinical examination on 30 March and the second on 28 March. The first confirmed H1N1/09 pandemic flu death, which occurred at Texas Children's Hospital in Houston, Texas, was of a toddler from Mexico City who was visiting family in Brownsville, Texas , before being air-lifted to Houston for treatment. The Infectious Diseases Society of America estimated that the total number of deaths in the U.S. was 12,469. Influenza surveillance information "answers the questions of where, when, and what influenza viruses are circulating. Sharing of such information is especially crucial during an emergent pandemic as in April 2009, when the genetic sequences of the initial viruses were rapidly and openly shared via the GISAID Initiative within days of identification, playing a key role in facilitating an early response to the evolving pandemic. Surveillance is used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza." For example, as of late June, influenza surveillance information showed the U.S. had nearly 28,000 laboratory-confirmed cases including 3,065 hospitalizations and 127 deaths. But mathematical modelling showed an estimated 1 million Americans had the 2009 pandemic flu at the time, according to Lyn Finelli , a flu surveillance official with the CDC. Estimating deaths from influenza is also a complicated process. In 2005, influenza only appeared on the death certificates of 1,812 people in the US. The average annual US death toll from flu is, however, estimated to be 36,000. The CDC explains: "[I]nfluenza is infrequently listed on death certificates of people who die from flu-related complications" and hence, "Only counting deaths where influenza was included on a death certificate would be a gross underestimation of influenza's true impact." Influenza surveillance information on the 2009 H1N1 flu pandemic is available, but almost no studies attempted to estimate the total number of deaths attributable to H1N1 flu. Two studies were carried out by the CDC; the later of them estimated that between 7,070 and 13,930 deaths were attributable to H1N1 flu from April to 14 November 2009. During the same period, 1,642 deaths were officially confirmed as caused by H1N1 flu. The WHO stated in 2010 that total mortality (including unconfirmed or unreported deaths) from H1N1 flu was "unquestionably higher" than their own confirmed death statistics. The initial outbreak received a week of near-constant media attention. Epidemiologists cautioned that the number of cases reported in the early days of an outbreak can be very inaccurate and deceptive, due to several causes, among them selection bias , media bias and incorrect reporting by governments. Inaccuracies could also be caused by authorities in different countries looking at differing population groups. Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases. "[E]ven in developed countries the [numbers of flu deaths] are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness". Joseph S. Bresee, then CDC flu division's epidemiology chief and Michael Osterholm , director of the Center for Infectious Disease Research and Policy pointed out that millions of people have had H1N1 flu, usually in a mild form, so the numbers of laboratory-confirmed cases were actually meaningless, and in July 2009, the WHO stopped keeping count of individual cases and focused more on major outbreaks. A Wisconsin study published in the Journal of the American Medical Association in September 2010, reported that findings showed that the 2009 H1N1 flu was no more severe than the seasonal flu. "The risk of most serious complications was not elevated in adults or children", the study's authors wrote. "Children were disproportionately affected by 2009 H1N1 infection, but the perceived severity of symptoms and risk of serious outcomes were not increased." Children infected in the 2009 H1N1 flu pandemic were no more likely to be hospitalized with complications or get pneumonia than those who catch seasonal strains. About 1.5% of children with the H1N1 swine flu strain were hospitalized within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus. CDC illness and death estimates from April 2009 to April 2010, in the US are as follows: It has been stated that about 36,000 die from the seasonal flu in the U.S. each year, and this is frequently understood as an indication that the H1N1 strain was not as severe as seasonal influenza. The 36,000 estimate was presented in a 2003 study by CDC scientists and refers to a period from 1990 to 1991 through 1998–99. During those years, the number of estimated deaths ranged from 17,000 to 52,000, with an average of about 36,000. Throughout that decade, influenza A (H3N2) was the predominant virus during most of the seasons, and H3N2 influenza viruses are typically associated with higher death rates. The JAMA study also looked at seasonal influenza-associated deaths over a 23-year period, from 1976 to 1977 and 1998–99 with estimates of respiratory and circulatory influenza-associated deaths ranging from about 5,000 to about 52,000, and an average of about 25,000. CDC believes that the range of deaths over the past 31 years (~3,000 to ~49,000) is a more accurate representation of the unpredictability and variability of flu-associated deaths. The annual toll from seasonal influenza in the US between 1979 and 2001 is estimated at 41,400 deaths on average. Therefore, the H1N1 pandemic estimated mortality of 8,870 to 18,300 is just below the mid-range of estimates. The 2009 pandemic caused US hospitals to make significant preparations in terms of hospital surge capacities, especially within the emergency department and among vulnerable populations. In many cases, hospitals were relatively successful in making sure that those patients most severely affected by the influenza strain were able to be seen, treated, and discharged in an efficient manner. A case-study of the preparation, planning, mitigation, and response efforts during the fall of 2009 is that of the Children's Hospital of Philadelphia (CHOP) which took several steps to increase the emergency department (ED) surge capacity response. CHOP used portions of the main lobby area as an ED waiting room; several of the region's hospital-based outpatient facilities were in use during evening and weekend hours for non-emergency cases; the ED's 24-hour short-stay unit was utilized to care for ED patients in a longer-term capacity; non-board certified physicians (in pediatric emergency medicine) and inpatient-unit medical nurses were utilized for ED patient care; hospital units normally utilized for other medical or therapeutic purposes were transformed into ED patient rooms; and rooms normally used for only one patient were expanded to at least a capacity of 2. Annual influenza epidemics are estimated to affect 5–15% of the global population. Although most cases are mild, these epidemics still cause severe illness in 3–5 million people and 290,000–650,000 deaths worldwide every year. On average 41,400 people die of influenza-related illnesses each year in the United States, based on data collected between 1979 and 2001. In industrialised countries, severe illness and deaths occur mainly in the high-risk populations of infants, the elderly and chronically ill patients, although the H1N1 flu outbreak (like the 1918 Spanish flu ) differs in its tendency to affect younger, healthier people. In addition to these annual epidemics, Influenza A virus strains caused three global pandemics during the 20th century: the Spanish flu in 1918, Asian flu in 1957, and Hong Kong flu in 1968–69. These virus strains had undergone major genetic changes for which the population did not possess significant immunity . Recent genetic analysis has revealed that three-quarters, or six out of the eight genetic segments, of the 2009 flu pandemic strain arose from the North American swine flu strains circulating since 1998, when a new strain was first identified on a factory farm in North Carolina, and which was the first-ever reported triple-hybrid flu virus. The Spanish flu began with a wave of mild cases in the spring, followed by more deadly waves in the autumn, eventually killing hundreds of thousands in the United States and 50–100 million worldwide. The great majority of deaths in the 1918 flu pandemic were the result of secondary bacterial pneumonia. The influenza virus damaged the lining of the bronchial tubes and lungs of patients, allowing common bacteria from the nose and throat to infect their lungs. Subsequent pandemics have had many fewer fatalities due to the development of antibiotic medicines which can treat pneumonia. The influenza virus has caused several pandemic threats over the past century, including the pseudo-pandemic of 1947 (thought of as mild because although globally distributed, it caused relatively few deaths), the 1976 swine flu outbreak and the 1977 Russian flu , all caused by the H1N1 subtype. The world has been at an increased level of alert since the SARS epidemic in Southeast Asia (caused by the SARS coronavirus ). The level of preparedness was further increased and sustained with the advent of the H5N1 bird flu outbreaks because of H5N1's high fatality rate, although the strains currently prevalent have limited human-to-human transmission ( anthroponotic ) capability, or epidemicity. People who contracted influenza before 1957 appeared to have some immunity to H1N1 flu. According to Daniel Jernigan, head of flu epidemiology for the U.S. CDC "Tests on blood serum from older people showed that they had antibodies that attacked the new virus ... That does not mean that everyone over 52 is immune, since Americans and Mexicans older than that have died of the new flu". In June 2012, a model based study found that the number of deaths related to the H1N1 influenza may have been fifteen times higher than the reported laboratory confirmed deaths, with 80% of the respiratory and cardiovascular deaths in people younger than 65 years and 51% occurring in southeast Asia and Africa. A disproportionate number of pandemic deaths might have occurred in these regions and that efforts to prevent future influenza pandemics need to effectively target these regions. A WHO-supported 2013 study estimated that the 2009 global pandemic respiratory mortality was ~10-fold higher than the World Health Organization's laboratory-confirmed mortality count (18.631). Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons less than 65 years of age occurred, so that many more life-years were lost. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last nine months of 2009. The majority (62–85%) were attributed to persons under 65 years of age. The burden varied greatly among countries. There was an almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000–249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 years of age. The COVID-19 pandemic is not caused by an influenza virus but SARS-CoV-2 , a coronavirus which also primarily affects the respiratory system.

Wiki

Pandemic influenza

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Influenza

Influenza , commonly known as " the flu " or just " flu ", is an infectious disease caused by influenza viruses . Symptoms range from mild to severe and often include fever , runny nose , sore throat , muscle pain , headache , coughing , and fatigue . These symptoms begin one to four days after exposure to the virus (typically two days) and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia from the virus or a subsequent bacterial infection. Other complications include acute respiratory distress syndrome , meningitis , encephalitis , and worsening of pre-existing health problems such as asthma and cardiovascular disease . There are four types of influenza virus: A, B, C, and D. Aquatic birds are the primary source of Influenza A virus (IAV), which is also widespread in various mammals, including humans and pigs. Influenza B virus (IBV) and Influenza C virus (ICV) primarily infect humans, and Influenza D virus (IDV) is found in cattle and pigs. IAV and IBV circulate in humans and cause seasonal epidemics, and ICV causes a mild infection, primarily in children. IDV can infect humans but is not known to cause illness. In humans, influenza viruses are primarily transmitted through respiratory droplets from coughing and sneezing. Transmission through aerosols and surfaces contaminated by the virus also occur. Frequent hand washing and covering one's mouth and nose when coughing and sneezing reduce transmission. Annual vaccination can help to provide protection against influenza. Influenza viruses, particularly IAV, evolve quickly, so flu vaccines are updated regularly to match which influenza strains are in circulation. Vaccines provide protection against IAV subtypes H1N1 and H3N2 and one or two IBV subtypes. Influenza infection is diagnosed with laboratory methods such as antibody or antigen tests and a polymerase chain reaction ( PCR ) to identify viral nucleic acid. The disease can be treated with supportive measures and, in severe cases, with antiviral drugs such as oseltamivir . In healthy individuals, influenza is typically self-limiting and rarely fatal, but it can be deadly in high-risk groups. In a typical year, 5–15% of the population contracts influenza. There are 3–5 million severe cases annually, with up to 650,000 respiratory-related deaths globally each year. Deaths most commonly occur in high-risk groups, including young children, the elderly, and people with chronic health conditions. In temperate regions of the world, the number of influenza cases peaks during winter, whereas in the tropics influenza can occur year-round. Since the late 1800s, large outbreaks of novel influenza strains that spread globally, called pandemics, have occurred every 10–50 years. Five flu pandemics have occurred since 1900: the Spanish flu in 1918–1920, which was the most severe flu pandemic, the Asian flu in 1957, the Hong Kong flu in 1968, the Russian flu in 1977, and the swine flu pandemic in 2009.The symptoms of influenza are similar to those of a cold, although usually more severe and less likely to include a runny nose . The time between exposure to the virus and development of symptoms, called the incubation period , is 1–4 days, most commonly 1–2 days. Many infections, however, are asymptomatic. The onset of symptoms is sudden, and initial symptoms are predominately non-specific, including fever, chills, headaches, muscle pain or aching , a feeling of discomfort , loss of appetite , lack of energy/fatigue, and confusion. These symptoms are usually accompanied by respiratory symptoms such as a dry cough, sore or dry throat, hoarse voice, and a stuffy or runny nose. Coughing is the most common symptom. Gastrointestinal symptoms may also occur, including nausea, vomiting, diarrhea, and gastroenteritis, especially in children. The standard influenza symptoms typically last for 2–8 days. A 2021 study suggests influenza can cause long lasting symptoms in a similar way to long COVID . Symptomatic infections are usually mild and limited to the upper respiratory tract, but progression to pneumonia is relatively common. Pneumonia may be caused by the primary viral infection or by a secondary bacterial infection. Primary pneumonia is characterized by rapid progression of fever, cough, labored breathing, and low oxygen levels that cause bluish skin. It is especially common among those who have an underlying cardiovascular disease such as rheumatic heart disease. Secondary pneumonia typically has a period of improvement in symptoms for 1–3 weeks followed by recurrent fever, sputum production, and fluid buildup in the lungs, but can also occur just a few days after influenza symptoms appear. About a third of primary pneumonia cases are followed by secondary pneumonia, which is most frequently caused by the bacteria Streptococcus pneumoniae and Staphylococcus aureus . Influenza viruses comprise four species. Each of the four species is the sole member of its own genus, and the four influenza genera comprise four of the seven genera in the family Orthomyxoviridae . They are: IAV is responsible for most cases of severe illness as well as seasonal epidemics and occasional pandemics. It infects people of all ages but tends to disproportionately cause severe illness in the elderly, the very young, and those who have chronic health issues. Birds are the primary reservoir of IAV, especially aquatic birds such as ducks, geese, shorebirds, and gulls, but the virus also circulates among mammals, including pigs, horses, and marine mammals. IAV is classified into subtypes based on the viral proteins haemagglutinin (H) and neuraminidase (N). As of 2019, 18 H subtypes and 11 N subtypes have been identified. Most potential combinations have been reported in birds, but H17-18 and N10-11 have only been found in bats. Only H subtypes H1-3 and N subtypes N1-2 are known to have circulated in humans. The IAV subtypes in circulation as of 2018 [ update ] are H1N1 and H3N2. IAVs can be classified more specifically by natural host species, geographical origin, year of isolation, and strain number, such as H1N1/A/duck/Alberta/35/76. IBV mainly infects humans but has been identified in seals, horses, dogs, and pigs. IBV does not have subtypes like IAV but has two antigenically distinct lineages, termed the B/Victoria/2/1987-like and B/Yamagata/16/1988-like lineages, or simply (B/)Victoria(-like) and (B/)Yamagata(-like). Both lineages are in circulation in humans, disproportionately affecting children. IBVs contribute to seasonal epidemics alongside IAVs but have never been associated with a pandemic. ICV, like IBV, is primarily found in humans, though it also has been detected in pigs, feral dogs, dromedary camels, cattle, and dogs. ICV infection primarily affects children and is usually asymptomatic or has mild cold-like symptoms, though more severe symptoms such as gastroenteritis and pneumonia can occur. Unlike IAV and IBV, ICV has not been a major focus of research pertaining to antiviral drugs, vaccines, and other measures against influenza. ICV is subclassified into six genetic/antigenic lineages. IDV has been isolated from pigs and cattle, the latter being the natural reservoir. Infection has also been observed in humans, horses, dromedary camels, and small ruminants such as goats and sheep. IDV is distantly related to ICV. While cattle workers have occasionally tested positive to prior IDV infection, it is not known to cause disease in humans. ICV and IDV experience a slower rate of antigenic evolution than IAV and IBV. Because of this antigenic stability, relatively few novel lineages emerge. Influenza viruses have a negative-sense , single-stranded RNA genome that is segmented. The negative sense of the genome means it can be used as a template to synthesize messenger RNA (mRNA). IAV and IBV have eight genome segments that encode 10 major proteins. ICV and IDV have seven genome segments that encode nine major proteins. Three segments encode three subunits of an RNA-dependent RNA polymerase (RdRp) complex: PB1, a transcriptase, PB2, which recognizes 5' caps, and PA (P3 for ICV and IDV), an endonuclease. The matrix protein (M1) and membrane protein (M2) share a segment, as do the non-structural protein (NS1) and the nuclear export protein (NEP). For IAV and IBV, hemagglutinin (HA) and neuraminidase (NA) are encoded on one segment each, whereas ICV and IDV encode a hemagglutinin-esterase fusion (HEF) protein on one segment that merges the functions of HA and NA. The final genome segment encodes the viral nucleoprotein (NP). Influenza viruses also encode various accessory proteins, such as PB1-F2 and PA-X, that are expressed through alternative open reading frames and which are important in host defense suppression, virulence, and pathogenicity. The virus particle, called a virion, is pleomorphic and varies between being filamentous, bacilliform, or spherical in shape. Clinical isolates tend to be pleomorphic, whereas strains adapted to laboratory growth typically produce spherical virions. Filamentous virions are about 250 nanometers (nm) by 80 nm, bacilliform 120–250 by 95 nm, and spherical 120 nm in diameter. The virion consists of each segment of the genome bound to nucleoproteins in separate ribonucleoprotein (RNP) complexes for each segment, all of which are surrounded by a lipid bilayer membrane called the viral envelope . There is a copy of the RdRp, all subunits included, bound to each RNP. The envelope is reinforced structurally by matrix proteins on the interior that enclose the RNPs, and the envelope contains HA and NA (or HEF ) proteins extending outward from the exterior surface of the envelope. HA and HEF proteins have a distinct "head" and "stalk" structure. M2 proteins form proton ion channels through the viral envelope that are required for viral entry and exit. IBVs contain a surface protein named NB that is anchored in the envelope, but its function is unknown. The viral life cycle begins by binding to a target cell. Binding is mediated by the viral HA proteins on the surface of the envelope, which bind to cells that contain sialic acid receptors on the surface of the cell membrane. For N1 subtypes with the "G147R" mutation and N2 subtypes, the NA protein can initiate entry. Prior to binding, NA proteins promote access to target cells by degrading mucus, which helps to remove extracellular decoy receptors that would impede access to target cells. After binding, the virus is internalized into the cell by an endosome that contains the virion inside it. The endosome is acidified by cellular vATPase to have lower pH, which triggers a conformational change in HA that allows fusion of the viral envelope with the endosomal membrane. At the same time, hydrogen ions diffuse into the virion through M2 ion channels, disrupting internal protein-protein interactions to release RNPs into the host cell's cytosol . The M1 protein shell surrounding RNPs is degraded, fully uncoating RNPs in the cytosol. RNPs are then imported into the nucleus with the help of viral localization signals. There, the viral RNA polymerase transcribes mRNA using the genomic negative-sense strand as a template. The polymerase snatches 5' caps for viral mRNA from cellular RNA to prime mRNA synthesis and the 3'-end of mRNA is polyadenylated at the end of transcription. Once viral mRNA is transcribed, it is exported out of the nucleus and translated by host ribosomes in a cap-dependent manner to synthesize viral proteins. RdRp also synthesizes complementary positive-sense strands of the viral genome in a complementary RNP complex which are then used as templates by viral polymerases to synthesize copies of the negative-sense genome. During these processes, RdRps of avian influenza viruses (AIVs) function optimally at a higher temperature than mammalian influenza viruses. Newly synthesized viral polymerase subunits and NP proteins are imported to the nucleus to further increase the rate of viral replication and form RNPs. HA, NA, and M2 proteins are trafficked with the aid of M1 and NEP proteins to the cell membrane through the Golgi apparatus and inserted into the cell's membrane. Viral non-structural proteins including NS1, PB1-F2, and PA-X regulate host cellular processes to disable antiviral responses. PB1-F2 also interacts with PB1 to keep polymerases in the nucleus longer. M1 and NEP proteins localize to the nucleus during the later stages of infection, bind to viral RNPs and mediate their export to the cytoplasm where they migrate to the cell membrane with the aid of recycled endosomes and are bundled into the segments of the genome. Progeny viruses leave the cell by budding from the cell membrane, which is initiated by the accumulation of M1 proteins at the cytoplasmic side of the membrane. The viral genome is incorporated inside a viral envelope derived from portions of the cell membrane that have HA, NA, and M2 proteins. At the end of budding, HA proteins remain attached to cellular sialic acid until they are cleaved by the sialidase activity of NA proteins. The virion is then released from the cell. The sialidase activity of NA also cleaves any sialic acid residues from the viral surface, which helps prevent newly assembled viruses from aggregating near the cell surface and improving infectivity. Similar to other aspects of influenza replication, optimal NA activity is temperature- and pH-dependent. Ultimately, presence of large quantities of viral RNA in the cell triggers apoptosis, i.e. programmed cell death, which is initiated by cellular factors to restrict viral replication. Two key processes that influenza viruses evolve through are antigenic drift and antigenic shift . Antigenic drift is when an influenza virus' antigens change due to the gradual accumulation of mutations in the antigen's (HA or NA) gene. This can occur in response to evolutionary pressure exerted by the host immune response. Antigenic drift is especially common for the HA protein, in which just a few amino acid changes in the head region can constitute antigenic drift. The result is the production of novel strains that can evade pre-existing antibody-mediated immunity. Antigenic drift occurs in all influenza species but is slower in B than A and slowest in C and D. Antigenic drift is a major cause of seasonal influenza, and requires that flu vaccines be updated annually. HA is the main component of inactivated vaccines, so surveillance monitors antigenic drift of this antigen among circulating strains. Antigenic evolution of influenza viruses of humans appears to be faster than influenza viruses in swine and equines. In wild birds, within-subtype antigenic variation appears to be limited but has been observed in poultry. Antigenic shift is a sudden, drastic change in an influenza virus' antigen, usually HA. During antigenic shift, antigenically different strains that infect the same cell can reassort genome segments with each other, producing hybrid progeny. Since all influenza viruses have segmented genomes, all are capable of reassortment. Antigenic shift, however, only occurs among influenza viruses of the same genus and most commonly occurs among IAVs. In particular, reassortment is very common in AIVs, creating a large diversity of influenza viruses in birds, but is uncommon in human, equine, and canine lineages. Pigs, bats, and quails have receptors for both mammalian and avian IAVs, so they are potential "mixing vessels" for reassortment. If an animal strain reassorts with a human strain, then a novel strain can emerge that is capable of human-to-human transmission. This has caused pandemics, but only a limited number have occurred, so it is difficult to predict when the next will happen. Influenza viruses comprise four species. Each of the four species is the sole member of its own genus, and the four influenza genera comprise four of the seven genera in the family Orthomyxoviridae . They are: IAV is responsible for most cases of severe illness as well as seasonal epidemics and occasional pandemics. It infects people of all ages but tends to disproportionately cause severe illness in the elderly, the very young, and those who have chronic health issues. Birds are the primary reservoir of IAV, especially aquatic birds such as ducks, geese, shorebirds, and gulls, but the virus also circulates among mammals, including pigs, horses, and marine mammals. IAV is classified into subtypes based on the viral proteins haemagglutinin (H) and neuraminidase (N). As of 2019, 18 H subtypes and 11 N subtypes have been identified. Most potential combinations have been reported in birds, but H17-18 and N10-11 have only been found in bats. Only H subtypes H1-3 and N subtypes N1-2 are known to have circulated in humans. The IAV subtypes in circulation as of 2018 [ update ] are H1N1 and H3N2. IAVs can be classified more specifically by natural host species, geographical origin, year of isolation, and strain number, such as H1N1/A/duck/Alberta/35/76. IBV mainly infects humans but has been identified in seals, horses, dogs, and pigs. IBV does not have subtypes like IAV but has two antigenically distinct lineages, termed the B/Victoria/2/1987-like and B/Yamagata/16/1988-like lineages, or simply (B/)Victoria(-like) and (B/)Yamagata(-like). Both lineages are in circulation in humans, disproportionately affecting children. IBVs contribute to seasonal epidemics alongside IAVs but have never been associated with a pandemic. ICV, like IBV, is primarily found in humans, though it also has been detected in pigs, feral dogs, dromedary camels, cattle, and dogs. ICV infection primarily affects children and is usually asymptomatic or has mild cold-like symptoms, though more severe symptoms such as gastroenteritis and pneumonia can occur. Unlike IAV and IBV, ICV has not been a major focus of research pertaining to antiviral drugs, vaccines, and other measures against influenza. ICV is subclassified into six genetic/antigenic lineages. IDV has been isolated from pigs and cattle, the latter being the natural reservoir. Infection has also been observed in humans, horses, dromedary camels, and small ruminants such as goats and sheep. IDV is distantly related to ICV. While cattle workers have occasionally tested positive to prior IDV infection, it is not known to cause disease in humans. ICV and IDV experience a slower rate of antigenic evolution than IAV and IBV. Because of this antigenic stability, relatively few novel lineages emerge. Influenza viruses have a negative-sense , single-stranded RNA genome that is segmented. The negative sense of the genome means it can be used as a template to synthesize messenger RNA (mRNA). IAV and IBV have eight genome segments that encode 10 major proteins. ICV and IDV have seven genome segments that encode nine major proteins. Three segments encode three subunits of an RNA-dependent RNA polymerase (RdRp) complex: PB1, a transcriptase, PB2, which recognizes 5' caps, and PA (P3 for ICV and IDV), an endonuclease. The matrix protein (M1) and membrane protein (M2) share a segment, as do the non-structural protein (NS1) and the nuclear export protein (NEP). For IAV and IBV, hemagglutinin (HA) and neuraminidase (NA) are encoded on one segment each, whereas ICV and IDV encode a hemagglutinin-esterase fusion (HEF) protein on one segment that merges the functions of HA and NA. The final genome segment encodes the viral nucleoprotein (NP). Influenza viruses also encode various accessory proteins, such as PB1-F2 and PA-X, that are expressed through alternative open reading frames and which are important in host defense suppression, virulence, and pathogenicity. The virus particle, called a virion, is pleomorphic and varies between being filamentous, bacilliform, or spherical in shape. Clinical isolates tend to be pleomorphic, whereas strains adapted to laboratory growth typically produce spherical virions. Filamentous virions are about 250 nanometers (nm) by 80 nm, bacilliform 120–250 by 95 nm, and spherical 120 nm in diameter. The virion consists of each segment of the genome bound to nucleoproteins in separate ribonucleoprotein (RNP) complexes for each segment, all of which are surrounded by a lipid bilayer membrane called the viral envelope . There is a copy of the RdRp, all subunits included, bound to each RNP. The envelope is reinforced structurally by matrix proteins on the interior that enclose the RNPs, and the envelope contains HA and NA (or HEF ) proteins extending outward from the exterior surface of the envelope. HA and HEF proteins have a distinct "head" and "stalk" structure. M2 proteins form proton ion channels through the viral envelope that are required for viral entry and exit. IBVs contain a surface protein named NB that is anchored in the envelope, but its function is unknown. The viral life cycle begins by binding to a target cell. Binding is mediated by the viral HA proteins on the surface of the envelope, which bind to cells that contain sialic acid receptors on the surface of the cell membrane. For N1 subtypes with the "G147R" mutation and N2 subtypes, the NA protein can initiate entry. Prior to binding, NA proteins promote access to target cells by degrading mucus, which helps to remove extracellular decoy receptors that would impede access to target cells. After binding, the virus is internalized into the cell by an endosome that contains the virion inside it. The endosome is acidified by cellular vATPase to have lower pH, which triggers a conformational change in HA that allows fusion of the viral envelope with the endosomal membrane. At the same time, hydrogen ions diffuse into the virion through M2 ion channels, disrupting internal protein-protein interactions to release RNPs into the host cell's cytosol . The M1 protein shell surrounding RNPs is degraded, fully uncoating RNPs in the cytosol. RNPs are then imported into the nucleus with the help of viral localization signals. There, the viral RNA polymerase transcribes mRNA using the genomic negative-sense strand as a template. The polymerase snatches 5' caps for viral mRNA from cellular RNA to prime mRNA synthesis and the 3'-end of mRNA is polyadenylated at the end of transcription. Once viral mRNA is transcribed, it is exported out of the nucleus and translated by host ribosomes in a cap-dependent manner to synthesize viral proteins. RdRp also synthesizes complementary positive-sense strands of the viral genome in a complementary RNP complex which are then used as templates by viral polymerases to synthesize copies of the negative-sense genome. During these processes, RdRps of avian influenza viruses (AIVs) function optimally at a higher temperature than mammalian influenza viruses. Newly synthesized viral polymerase subunits and NP proteins are imported to the nucleus to further increase the rate of viral replication and form RNPs. HA, NA, and M2 proteins are trafficked with the aid of M1 and NEP proteins to the cell membrane through the Golgi apparatus and inserted into the cell's membrane. Viral non-structural proteins including NS1, PB1-F2, and PA-X regulate host cellular processes to disable antiviral responses. PB1-F2 also interacts with PB1 to keep polymerases in the nucleus longer. M1 and NEP proteins localize to the nucleus during the later stages of infection, bind to viral RNPs and mediate their export to the cytoplasm where they migrate to the cell membrane with the aid of recycled endosomes and are bundled into the segments of the genome. Progeny viruses leave the cell by budding from the cell membrane, which is initiated by the accumulation of M1 proteins at the cytoplasmic side of the membrane. The viral genome is incorporated inside a viral envelope derived from portions of the cell membrane that have HA, NA, and M2 proteins. At the end of budding, HA proteins remain attached to cellular sialic acid until they are cleaved by the sialidase activity of NA proteins. The virion is then released from the cell. The sialidase activity of NA also cleaves any sialic acid residues from the viral surface, which helps prevent newly assembled viruses from aggregating near the cell surface and improving infectivity. Similar to other aspects of influenza replication, optimal NA activity is temperature- and pH-dependent. Ultimately, presence of large quantities of viral RNA in the cell triggers apoptosis, i.e. programmed cell death, which is initiated by cellular factors to restrict viral replication. Two key processes that influenza viruses evolve through are antigenic drift and antigenic shift . Antigenic drift is when an influenza virus' antigens change due to the gradual accumulation of mutations in the antigen's (HA or NA) gene. This can occur in response to evolutionary pressure exerted by the host immune response. Antigenic drift is especially common for the HA protein, in which just a few amino acid changes in the head region can constitute antigenic drift. The result is the production of novel strains that can evade pre-existing antibody-mediated immunity. Antigenic drift occurs in all influenza species but is slower in B than A and slowest in C and D. Antigenic drift is a major cause of seasonal influenza, and requires that flu vaccines be updated annually. HA is the main component of inactivated vaccines, so surveillance monitors antigenic drift of this antigen among circulating strains. Antigenic evolution of influenza viruses of humans appears to be faster than influenza viruses in swine and equines. In wild birds, within-subtype antigenic variation appears to be limited but has been observed in poultry. Antigenic shift is a sudden, drastic change in an influenza virus' antigen, usually HA. During antigenic shift, antigenically different strains that infect the same cell can reassort genome segments with each other, producing hybrid progeny. Since all influenza viruses have segmented genomes, all are capable of reassortment. Antigenic shift, however, only occurs among influenza viruses of the same genus and most commonly occurs among IAVs. In particular, reassortment is very common in AIVs, creating a large diversity of influenza viruses in birds, but is uncommon in human, equine, and canine lineages. Pigs, bats, and quails have receptors for both mammalian and avian IAVs, so they are potential "mixing vessels" for reassortment. If an animal strain reassorts with a human strain, then a novel strain can emerge that is capable of human-to-human transmission. This has caused pandemics, but only a limited number have occurred, so it is difficult to predict when the next will happen. People who are infected can transmit influenza viruses through breathing, talking, coughing, and sneezing, which spread respiratory droplets and aerosols that contain virus particles into the air. A person susceptible to infection can then contract influenza by coming into contact with these particles. Respiratory droplets are relatively large and travel less than two meters before falling onto nearby surfaces. Aerosols are smaller and remain suspended in the air longer, so they take longer to settle and can travel further than respiratory droplets. Inhalation of aerosols can lead to infection, but most transmission is in the area about two meters around an infected person via respiratory droplets that come into contact with mucosa of the upper respiratory tract. Transmission through contact with a person, bodily fluids, or intermediate objects ( fomites ) can also occur, such as through contaminated hands and surfaces since influenza viruses can survive for hours on non-porous surfaces. If one's hands are contaminated, then touching one's face can cause infection. Influenza is usually transmissible from one day before the onset of symptoms to 5–7 days after. In healthy adults, the virus is shed for up to 3–5 days. In children and the immunocompromised, the virus may be transmissible for several weeks. Children ages 2–17 are considered to be the primary and most efficient spreaders of influenza. Children who have not had multiple prior exposures to influenza viruses shed the virus at greater quantities and for a longer duration than other children. People who are at risk of exposure to influenza include health care workers, social care workers, and those who live with or care for people vulnerable to influenza. In long-term care facilities, the flu can spread rapidly after it is introduced. A variety of factors likely encourage influenza transmission, including lower temperature, lower absolute and relative humidity , less ultraviolet radiation from the Sun, and crowding. Influenza viruses that infect the upper respiratory tract like H1N1 tend to be more mild but more transmissible, whereas those that infect the lower respiratory tract like H5N1 tend to cause more severe illness but are less contagious. In humans, influenza viruses first cause infection by infecting epithelial cells in the respiratory tract. Illness during infection is primarily the result of lung inflammation and compromise caused by epithelial cell infection and death, combined with inflammation caused by the immune system's response to infection. Non-respiratory organs can become involved, but the mechanisms by which influenza is involved in these cases are unknown. Severe respiratory illness can be caused by multiple, non-exclusive mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity due to epithelial cell infection and death, and degradation of the extracellular matrix that maintains lung structure. In particular, alveolar cell infection appears to drive severe symptoms since this results in impaired gas exchange and enables viruses to infect endothelial cells, which produce large quantities of pro-inflammatory cytokines . Pneumonia caused by influenza viruses is characterized by high levels of viral replication in the lower respiratory tract, accompanied by a strong pro-inflammatory response called a cytokine storm . Infection with H5N1 or H7N9 especially produces high levels of pro-inflammatory cytokines. In bacterial infections, early depletion of macrophages during influenza creates a favorable environment in the lungs for bacterial growth since these white blood cells are important in responding to bacterial infection. Host mechanisms to encourage tissue repair may inadvertently allow bacterial infection. Infection also induces production of systemic glucocorticoids that can reduce inflammation to preserve tissue integrity but allow increased bacterial growth. The pathophysiology of influenza is significantly influenced by which receptors influenza viruses bind to during entry into cells. Mammalian influenza viruses preferentially bind to sialic acids connected to the rest of the oligosaccharide by an α-2,6 link, most commonly found in various respiratory cells, such as respiratory and retinal epithelial cells. AIVs prefer sialic acids with an α-2,3 linkage, which are most common in birds in gastrointestinal epithelial cells and in humans in the lower respiratory tract. Furthermore, cleavage of the HA protein into HA 1 , the binding subunit, and HA 2 , the fusion subunit, is performed by different proteases, affecting which cells can be infected. For mammalian influenza viruses and low pathogenic AIVs, cleavage is extracellular, which limits infection to cells that have the appropriate proteases, whereas for highly pathogenic AIVs, cleavage is intracellular and performed by ubiquitous proteases, which allows for infection of a greater variety of cells, thereby contributing to more severe disease. Cells possess sensors to detect viral RNA, which can then induce interferon production. Interferons mediate expression of antiviral proteins and proteins that recruit immune cells to the infection site, and they also notify nearby uninfected cells of infection. Some infected cells release pro-inflammatory cytokines that recruit immune cells to the site of infection. Immune cells control viral infection by killing infected cells and phagocytizing viral particles and apoptotic cells. An exacerbated immune response, however, can harm the host organism through a cytokine storm. To counter the immune response, influenza viruses encode various non-structural proteins, including NS1, NEP, PB1-F2, and PA-X, that are involved in curtailing the host immune response by suppressing interferon production and host gene expression. B cells , a type of white blood cell, produce antibodies that bind to influenza antigens HA and NA (or HEF ) and other proteins to a lesser degree. Once bound to these proteins, antibodies block virions from binding to cellular receptors, neutralizing the virus. In humans, a sizeable antibody response occurs ~1 week after viral exposure. This antibody response is typically robust and long-lasting, especially for ICV and IDV. In other words, people exposed to a certain strain in childhood still possess antibodies to that strain at a reasonable level later in life, which can provide some protection to related strains. There is, however, an " original antigenic sin ", in which the first HA subtype a person is exposed to influences the antibody-based immune response to future infections and vaccines. People who are infected can transmit influenza viruses through breathing, talking, coughing, and sneezing, which spread respiratory droplets and aerosols that contain virus particles into the air. A person susceptible to infection can then contract influenza by coming into contact with these particles. Respiratory droplets are relatively large and travel less than two meters before falling onto nearby surfaces. Aerosols are smaller and remain suspended in the air longer, so they take longer to settle and can travel further than respiratory droplets. Inhalation of aerosols can lead to infection, but most transmission is in the area about two meters around an infected person via respiratory droplets that come into contact with mucosa of the upper respiratory tract. Transmission through contact with a person, bodily fluids, or intermediate objects ( fomites ) can also occur, such as through contaminated hands and surfaces since influenza viruses can survive for hours on non-porous surfaces. If one's hands are contaminated, then touching one's face can cause infection. Influenza is usually transmissible from one day before the onset of symptoms to 5–7 days after. In healthy adults, the virus is shed for up to 3–5 days. In children and the immunocompromised, the virus may be transmissible for several weeks. Children ages 2–17 are considered to be the primary and most efficient spreaders of influenza. Children who have not had multiple prior exposures to influenza viruses shed the virus at greater quantities and for a longer duration than other children. People who are at risk of exposure to influenza include health care workers, social care workers, and those who live with or care for people vulnerable to influenza. In long-term care facilities, the flu can spread rapidly after it is introduced. A variety of factors likely encourage influenza transmission, including lower temperature, lower absolute and relative humidity , less ultraviolet radiation from the Sun, and crowding. Influenza viruses that infect the upper respiratory tract like H1N1 tend to be more mild but more transmissible, whereas those that infect the lower respiratory tract like H5N1 tend to cause more severe illness but are less contagious. In humans, influenza viruses first cause infection by infecting epithelial cells in the respiratory tract. Illness during infection is primarily the result of lung inflammation and compromise caused by epithelial cell infection and death, combined with inflammation caused by the immune system's response to infection. Non-respiratory organs can become involved, but the mechanisms by which influenza is involved in these cases are unknown. Severe respiratory illness can be caused by multiple, non-exclusive mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity due to epithelial cell infection and death, and degradation of the extracellular matrix that maintains lung structure. In particular, alveolar cell infection appears to drive severe symptoms since this results in impaired gas exchange and enables viruses to infect endothelial cells, which produce large quantities of pro-inflammatory cytokines . Pneumonia caused by influenza viruses is characterized by high levels of viral replication in the lower respiratory tract, accompanied by a strong pro-inflammatory response called a cytokine storm . Infection with H5N1 or H7N9 especially produces high levels of pro-inflammatory cytokines. In bacterial infections, early depletion of macrophages during influenza creates a favorable environment in the lungs for bacterial growth since these white blood cells are important in responding to bacterial infection. Host mechanisms to encourage tissue repair may inadvertently allow bacterial infection. Infection also induces production of systemic glucocorticoids that can reduce inflammation to preserve tissue integrity but allow increased bacterial growth. The pathophysiology of influenza is significantly influenced by which receptors influenza viruses bind to during entry into cells. Mammalian influenza viruses preferentially bind to sialic acids connected to the rest of the oligosaccharide by an α-2,6 link, most commonly found in various respiratory cells, such as respiratory and retinal epithelial cells. AIVs prefer sialic acids with an α-2,3 linkage, which are most common in birds in gastrointestinal epithelial cells and in humans in the lower respiratory tract. Furthermore, cleavage of the HA protein into HA 1 , the binding subunit, and HA 2 , the fusion subunit, is performed by different proteases, affecting which cells can be infected. For mammalian influenza viruses and low pathogenic AIVs, cleavage is extracellular, which limits infection to cells that have the appropriate proteases, whereas for highly pathogenic AIVs, cleavage is intracellular and performed by ubiquitous proteases, which allows for infection of a greater variety of cells, thereby contributing to more severe disease. Cells possess sensors to detect viral RNA, which can then induce interferon production. Interferons mediate expression of antiviral proteins and proteins that recruit immune cells to the infection site, and they also notify nearby uninfected cells of infection. Some infected cells release pro-inflammatory cytokines that recruit immune cells to the site of infection. Immune cells control viral infection by killing infected cells and phagocytizing viral particles and apoptotic cells. An exacerbated immune response, however, can harm the host organism through a cytokine storm. To counter the immune response, influenza viruses encode various non-structural proteins, including NS1, NEP, PB1-F2, and PA-X, that are involved in curtailing the host immune response by suppressing interferon production and host gene expression. B cells , a type of white blood cell, produce antibodies that bind to influenza antigens HA and NA (or HEF ) and other proteins to a lesser degree. Once bound to these proteins, antibodies block virions from binding to cellular receptors, neutralizing the virus. In humans, a sizeable antibody response occurs ~1 week after viral exposure. This antibody response is typically robust and long-lasting, especially for ICV and IDV. In other words, people exposed to a certain strain in childhood still possess antibodies to that strain at a reasonable level later in life, which can provide some protection to related strains. There is, however, an " original antigenic sin ", in which the first HA subtype a person is exposed to influences the antibody-based immune response to future infections and vaccines. Annual vaccination is the primary and most effective way to prevent influenza and influenza-associated complications, especially for high-risk groups. Vaccines against the flu are trivalent or quadrivalent, providing protection against an H1N1 strain, an H3N2 strain, and one or two IBV strains corresponding to the two IBV lineages. Two types of vaccines are in use: inactivated vaccines that contain "killed" (i.e. inactivated) viruses and live attenuated influenza vaccines (LAIVs) that contain weakened viruses. There are three types of inactivated vaccines: whole virus, split virus, in which the virus is disrupted by a detergent, and subunit, which only contains the viral antigens HA and NA. Most flu vaccines are inactivated and administered via intramuscular injection. LAIVs are sprayed into the nasal cavity. Vaccination recommendations vary by country. Some recommend vaccination for all people above a certain age, such as 6 months, whereas other countries limit recommendations to high-risk groups. Young infants cannot receive flu vaccines for safety reasons, but they can inherit passive immunity from their mother if inactivated vaccines are administered to the mother during pregnancy. Influenza vaccination helps to reduce the probability of reassortment. In general, influenza vaccines are only effective if there is an antigenic match between vaccine strains and circulating strains. Additionally, most commercially available flu vaccines are manufactured by propagation of influenza viruses in embryonated chicken eggs, taking 6–8 months. Flu seasons are different in the northern and southern hemisphere, so the WHO meets twice a year, one for each hemisphere, to discuss which strains should be included in flu vaccines based on observation from HA inhibition assays. Other manufacturing methods include an MDCK cell culture-based inactivated vaccine and a recombinant subunit vaccine manufactured from baculovirus overexpression in insect cells. Influenza can be prevented or reduced in severity by post-exposure prophylaxis with the antiviral drugs oseltamivir , which can be taken orally by those at least three months old, and zanamivir , which can be inhaled by those above seven years of age. Chemoprophylaxis is most useful for individuals at high-risk of developing complications and those who cannot receive the flu vaccine due to contraindications or lack of effectiveness. Post-exposure chemoprophylaxis is only recommended if oseltamivir is taken within 48 hours of contact with a confirmed or suspected influenza case and zanamivir within 36 hours. It is recommended that it be offered to people who have yet to receive a vaccine for the current flu season, who have been vaccinated less than two week since contact, if there is a significant mismatch between vaccine and circulating strains, or during an outbreak in a closed setting regardless of vaccination history. Hand hygiene is important in reducing the spread of influenza. This includes frequent hand washing with soap and water, using alcohol -based hand sanitizers , and not touching one's eyes, nose, and mouth with one's hands. Covering one's nose and mouth when coughing or sneezing is important. Other methods to limit influenza transmission include staying home when sick, avoiding contact with others until one day after symptoms end, and disinfecting surfaces likely to be contaminated by the virus. Health education through media and posters is often used to remind people of hygiene. There is uncertainty about the use of masks since research thus far has not shown a significant reduction in seasonal influenza with mask usage. Likewise, the effectiveness of screening at points of entry into countries is not well researched. Social distancing measures such as school closures, avoiding contact with infected people via isolation or quarantine, and limiting mass gatherings may reduce transmission, but these measures are often expensive, unpopular, and difficult to implement. Consequently, the commonly recommended methods of infection control are respiratory etiquette, hand hygiene, and mask wearing, which are inexpensive and easy to perform. Pharmaceutical measures are effective but may not be available in the early stages of an outbreak. In health care settings, infected individuals may be cohorted or assigned to individual rooms. Protective clothing such as masks, gloves, and gowns is recommended when coming into contact with infected individuals if there is a risk of exposure to infected bodily fluids. Keeping patients in negative pressure rooms and avoiding aerosol-producing activities may help, but special air handling and ventilation systems are not considered necessary to prevent the spread of influenza in the air. In residential homes, new admissions may need to be closed until the spread of influenza is controlled. When discharging patients to care homes, it is important to take care if there is a known influenza outbreak. Since influenza viruses circulate in animals such as birds and pigs, prevention of transmission from these animals is important. Water treatment , indoor raising of animals, quarantining sick animals, vaccination, and biosecurity are the primary measures used. Placing poultry houses and piggeries on high ground away from high-density farms, backyard farms, live poultry markets, and bodies of water helps to minimize contact with wild birds. Closure of live poultry markets appears to the most effective measure and has shown to be effective at controlling the spread of H5N1, H7N9, and H9N2 . Other biosecurity measures include cleaning and disinfecting facilities and vehicles, banning visits to poultry farms, not bringing birds intended for slaughter back to farms, changing clothes, disinfecting foot baths, and treating food and water. If live poultry markets are not closed, then "clean days" when unsold poultry is removed and facilities are disinfected and "no carry-over" policies to eliminate infectious material before new poultry arrive can be used to reduce the spread of influenza viruses. If a novel influenza viruses has breached the aforementioned biosecurity measures, then rapid detection to stamp it out via quarantining, decontamination, and culling may be necessary to prevent the virus from becoming endemic. Vaccines exist for avian H5, H7, and H9 subtypes that are used in some countries. In China, for example, vaccination of domestic birds against H7N9 successfully limited its spread, indicating that vaccination may be an effective strategy if used in combination with other measures to limit transmission. In pigs and horses, management of influenza is dependent on vaccination with biosecurity. Annual vaccination is the primary and most effective way to prevent influenza and influenza-associated complications, especially for high-risk groups. Vaccines against the flu are trivalent or quadrivalent, providing protection against an H1N1 strain, an H3N2 strain, and one or two IBV strains corresponding to the two IBV lineages. Two types of vaccines are in use: inactivated vaccines that contain "killed" (i.e. inactivated) viruses and live attenuated influenza vaccines (LAIVs) that contain weakened viruses. There are three types of inactivated vaccines: whole virus, split virus, in which the virus is disrupted by a detergent, and subunit, which only contains the viral antigens HA and NA. Most flu vaccines are inactivated and administered via intramuscular injection. LAIVs are sprayed into the nasal cavity. Vaccination recommendations vary by country. Some recommend vaccination for all people above a certain age, such as 6 months, whereas other countries limit recommendations to high-risk groups. Young infants cannot receive flu vaccines for safety reasons, but they can inherit passive immunity from their mother if inactivated vaccines are administered to the mother during pregnancy. Influenza vaccination helps to reduce the probability of reassortment. In general, influenza vaccines are only effective if there is an antigenic match between vaccine strains and circulating strains. Additionally, most commercially available flu vaccines are manufactured by propagation of influenza viruses in embryonated chicken eggs, taking 6–8 months. Flu seasons are different in the northern and southern hemisphere, so the WHO meets twice a year, one for each hemisphere, to discuss which strains should be included in flu vaccines based on observation from HA inhibition assays. Other manufacturing methods include an MDCK cell culture-based inactivated vaccine and a recombinant subunit vaccine manufactured from baculovirus overexpression in insect cells. Influenza can be prevented or reduced in severity by post-exposure prophylaxis with the antiviral drugs oseltamivir , which can be taken orally by those at least three months old, and zanamivir , which can be inhaled by those above seven years of age. Chemoprophylaxis is most useful for individuals at high-risk of developing complications and those who cannot receive the flu vaccine due to contraindications or lack of effectiveness. Post-exposure chemoprophylaxis is only recommended if oseltamivir is taken within 48 hours of contact with a confirmed or suspected influenza case and zanamivir within 36 hours. It is recommended that it be offered to people who have yet to receive a vaccine for the current flu season, who have been vaccinated less than two week since contact, if there is a significant mismatch between vaccine and circulating strains, or during an outbreak in a closed setting regardless of vaccination history. Hand hygiene is important in reducing the spread of influenza. This includes frequent hand washing with soap and water, using alcohol -based hand sanitizers , and not touching one's eyes, nose, and mouth with one's hands. Covering one's nose and mouth when coughing or sneezing is important. Other methods to limit influenza transmission include staying home when sick, avoiding contact with others until one day after symptoms end, and disinfecting surfaces likely to be contaminated by the virus. Health education through media and posters is often used to remind people of hygiene. There is uncertainty about the use of masks since research thus far has not shown a significant reduction in seasonal influenza with mask usage. Likewise, the effectiveness of screening at points of entry into countries is not well researched. Social distancing measures such as school closures, avoiding contact with infected people via isolation or quarantine, and limiting mass gatherings may reduce transmission, but these measures are often expensive, unpopular, and difficult to implement. Consequently, the commonly recommended methods of infection control are respiratory etiquette, hand hygiene, and mask wearing, which are inexpensive and easy to perform. Pharmaceutical measures are effective but may not be available in the early stages of an outbreak. In health care settings, infected individuals may be cohorted or assigned to individual rooms. Protective clothing such as masks, gloves, and gowns is recommended when coming into contact with infected individuals if there is a risk of exposure to infected bodily fluids. Keeping patients in negative pressure rooms and avoiding aerosol-producing activities may help, but special air handling and ventilation systems are not considered necessary to prevent the spread of influenza in the air. In residential homes, new admissions may need to be closed until the spread of influenza is controlled. When discharging patients to care homes, it is important to take care if there is a known influenza outbreak. Since influenza viruses circulate in animals such as birds and pigs, prevention of transmission from these animals is important. Water treatment , indoor raising of animals, quarantining sick animals, vaccination, and biosecurity are the primary measures used. Placing poultry houses and piggeries on high ground away from high-density farms, backyard farms, live poultry markets, and bodies of water helps to minimize contact with wild birds. Closure of live poultry markets appears to the most effective measure and has shown to be effective at controlling the spread of H5N1, H7N9, and H9N2 . Other biosecurity measures include cleaning and disinfecting facilities and vehicles, banning visits to poultry farms, not bringing birds intended for slaughter back to farms, changing clothes, disinfecting foot baths, and treating food and water. If live poultry markets are not closed, then "clean days" when unsold poultry is removed and facilities are disinfected and "no carry-over" policies to eliminate infectious material before new poultry arrive can be used to reduce the spread of influenza viruses. If a novel influenza viruses has breached the aforementioned biosecurity measures, then rapid detection to stamp it out via quarantining, decontamination, and culling may be necessary to prevent the virus from becoming endemic. Vaccines exist for avian H5, H7, and H9 subtypes that are used in some countries. In China, for example, vaccination of domestic birds against H7N9 successfully limited its spread, indicating that vaccination may be an effective strategy if used in combination with other measures to limit transmission. In pigs and horses, management of influenza is dependent on vaccination with biosecurity. Diagnosis based on symptoms is fairly accurate in otherwise healthy people during seasonal epidemics and should be suspected in cases of pneumonia, acute respiratory distress syndrome (ARDS), sepsis , or if encephalitis, myocarditis , or breaking down of muscle tissue occur. Because influenza is similar to other viral respiratory tract illnesses, laboratory diagnosis is necessary for confirmation. Common ways of collecting samples for testing include nasal and throat swabs. Samples may be taken from the lower respiratory tract if infection has cleared the upper but not lower respiratory tract. Influenza testing is recommended for anyone hospitalized with symptoms resembling influenza during flu season or who is connected to an influenza case. For severe cases, earlier diagnosis improves patient outcome. Diagnostic methods that can identify influenza include viral cultures , antibody- and antigen-detecting tests, and nucleic acid-based tests. Viruses can be grown in a culture of mammalian cells or embryonated eggs for 3–10 days to monitor cytopathic effect. Final confirmation can then be done via antibody staining, hemadsorption using red blood cells , or immunofluorescence microscopy. Shell vial cultures, which can identify infection via immunostaining before a cytopathic effect appears, are more sensitive than traditional cultures with results in 1–3 days. Cultures can be used to characterize novel viruses, observe sensitivity to antiviral drugs, and monitor antigenic drift, but they are relatively slow and require specialized skills and equipment. Serological assays can be used to detect an antibody response to influenza after natural infection or vaccination. Common serological assays include hemagglutination inhibition assays that detect HA-specific antibodies, virus neutralization assays that check whether antibodies have neutralized the virus, and enzyme-linked immunoabsorbant assays. These methods tend to be relatively inexpensive and fast but are less reliable than nucleic-acid based tests. Direct fluorescent or immunofluorescent antibody (DFA/IFA) tests involve staining respiratory epithelial cells in samples with fluorescently-labeled influenza-specific antibodies, followed by examination under a fluorescent microscope. They can differentiate between IAV and IBV but can not subtype IAV. Rapid influenza diagnostic tests (RIDTs) are a simple way of obtaining assay results, are low cost, and produce results quickly, at less than 30 minutes, so they are commonly used, but they can not distinguish between IAV and IBV or between IAV subtypes and are not as sensitive as nucleic-acid based tests. Nucleic acid-based tests (NATs) amplify and detect viral nucleic acid. Most of these tests take a few hours, but rapid molecular assays are as fast as RIDTs. Among NATs, reverse transcription polymerase chain reaction (RT-PCR) is the most traditional and considered the gold standard for diagnosing influenza because it is fast and can subtype IAV, but it is relatively expensive and more prone to false-positives than cultures. Other NATs that have been used include loop-mediated isothermal amplification -based assays, simple amplification-based assays, and nucleic acid sequence-based amplification. Nucleic acid sequencing methods can identify infection by obtaining the nucleic acid sequence of viral samples to identify the virus and antiviral drug resistance. The traditional method is Sanger sequencing , but it has been largely replaced by next-generation methods that have greater sequencing speed and throughput. Treatment of influenza in cases of mild or moderate illness is supportive and includes anti-fever medications such as acetaminophen and ibuprofen , adequate fluid intake to avoid dehydration, and resting at home. Cough drops and throat sprays may be beneficial for sore throat. It is recommended to avoid alcohol and tobacco use while sick with the flu. Aspirin is not recommended to treat influenza in children due to an elevated risk of developing Reye syndrome. Corticosteroids likewise are not recommended except when treating septic shock or an underlying medical condition, such as chronic obstructive pulmonary disease or asthma exacerbation, since they are associated with increased mortality. If a secondary bacterial infection occurs, then treatment with antibiotics may be necessary. Antiviral drugs are primarily used to treat severely ill patients, especially those with compromised immune systems. Antivirals are most effective when started in the first 48 hours after symptoms appear. Later administration may still be beneficial for those who have underlying immune defects, those with more severe symptoms, or those who have a higher risk of developing complications if these individuals are still shedding the virus. Antiviral treatment is also recommended if a person is hospitalized with suspected influenza instead of waiting for test results to return and if symptoms are worsening. Most antiviral drugs against influenza fall into two categories: neuraminidase (NA) inhibitors and M2 inhibitors. Baloxavir marboxil is a notable exception, which targets the endonuclease activity of the viral RNA polymerase and can be used as an alternative to NA and M2 inhibitors for IAV and IBV. NA inhibitors target the enzymatic activity of NA receptors, mimicking the binding of sialic acid in the active site of NA on IAV and IBV virions so that viral release from infected cells and the rate of viral replication are impaired. NA inhibitors include oseltamivir, which is consumed orally in a prodrug form and converted to its active form in the liver, and zanamivir, which is a powder that is inhaled nasally. Oseltamivir and zanamivir are effective for prophylaxis and post-exposure prophylaxis, and research overall indicates that NA inhibitors are effective at reducing rates of complications, hospitalization, and mortality and the duration of illness. Additionally, the earlier NA inhibitors are provided, the better the outcome, though late administration can still be beneficial in severe cases. Other NA inhibitors include laninamivir and peramivir, the latter of which can be used as an alternative to oseltamivir for people who cannot tolerate or absorb it. The adamantanes amantadine and rimantadine are orally administered drugs that block the influenza virus' M2 ion channel, preventing viral uncoating. These drugs are only functional against IAV but are no longer recommended for use because of widespread resistance to them among IAVs. Adamantane resistance first emerged in H3N2 in 2003, becoming worldwide by 2008. Oseltamivir resistance is no longer widespread because the 2009 pandemic H1N1 strain (H1N1 pdm09), which is resistant to adamantanes, seemingly replaced resistant strains in circulation. Since the 2009 pandemic, oseltamivir resistance has mainly been observed in patients undergoing therapy, especially the immunocompromised and young children. Oseltamivir resistance is usually reported in H1N1, but has been reported in H3N2 and IBVs less commonly. Because of this, oseltamivir is recommended as the first drug of choice for immunocompetent people, whereas for the immunocompromised, oseltamivir is recommended against H3N2 and IBV and zanamivir against H1N1 pdm09. Zanamivir resistance is observed less frequently, and resistance to peramivir and baloxavir marboxil is possible. Antiviral drugs are primarily used to treat severely ill patients, especially those with compromised immune systems. Antivirals are most effective when started in the first 48 hours after symptoms appear. Later administration may still be beneficial for those who have underlying immune defects, those with more severe symptoms, or those who have a higher risk of developing complications if these individuals are still shedding the virus. Antiviral treatment is also recommended if a person is hospitalized with suspected influenza instead of waiting for test results to return and if symptoms are worsening. Most antiviral drugs against influenza fall into two categories: neuraminidase (NA) inhibitors and M2 inhibitors. Baloxavir marboxil is a notable exception, which targets the endonuclease activity of the viral RNA polymerase and can be used as an alternative to NA and M2 inhibitors for IAV and IBV. NA inhibitors target the enzymatic activity of NA receptors, mimicking the binding of sialic acid in the active site of NA on IAV and IBV virions so that viral release from infected cells and the rate of viral replication are impaired. NA inhibitors include oseltamivir, which is consumed orally in a prodrug form and converted to its active form in the liver, and zanamivir, which is a powder that is inhaled nasally. Oseltamivir and zanamivir are effective for prophylaxis and post-exposure prophylaxis, and research overall indicates that NA inhibitors are effective at reducing rates of complications, hospitalization, and mortality and the duration of illness. Additionally, the earlier NA inhibitors are provided, the better the outcome, though late administration can still be beneficial in severe cases. Other NA inhibitors include laninamivir and peramivir, the latter of which can be used as an alternative to oseltamivir for people who cannot tolerate or absorb it. The adamantanes amantadine and rimantadine are orally administered drugs that block the influenza virus' M2 ion channel, preventing viral uncoating. These drugs are only functional against IAV but are no longer recommended for use because of widespread resistance to them among IAVs. Adamantane resistance first emerged in H3N2 in 2003, becoming worldwide by 2008. Oseltamivir resistance is no longer widespread because the 2009 pandemic H1N1 strain (H1N1 pdm09), which is resistant to adamantanes, seemingly replaced resistant strains in circulation. Since the 2009 pandemic, oseltamivir resistance has mainly been observed in patients undergoing therapy, especially the immunocompromised and young children. Oseltamivir resistance is usually reported in H1N1, but has been reported in H3N2 and IBVs less commonly. Because of this, oseltamivir is recommended as the first drug of choice for immunocompetent people, whereas for the immunocompromised, oseltamivir is recommended against H3N2 and IBV and zanamivir against H1N1 pdm09. Zanamivir resistance is observed less frequently, and resistance to peramivir and baloxavir marboxil is possible. In healthy individuals, influenza infection is usually self-limiting and rarely fatal. Symptoms usually last for 2–8 days. Influenza can cause people to miss work or school, and it is associated with decreased job performance and, in older adults, reduced independence. Fatigue and malaise may last for several weeks after recovery, and healthy adults may experience pulmonary abnormalities that can take several weeks to resolve. Complications and mortality primarily occur in high-risk populations and those who are hospitalized. Severe disease and mortality are usually attributable to pneumonia from the primary viral infection or a secondary bacterial infection, which can progress to ARDS. Other respiratory complications that may occur include sinusitis , bronchitis , bronchiolitis , excess fluid buildup in the lungs, and exacerbation of chronic bronchitis and asthma. Middle ear infection and croup may occur, most commonly in children. Secondary S. aureus infection has been observed, primarily in children, to cause toxic shock syndrome after influenza, with hypotension, fever, and reddening and peeling of the skin. Complications affecting the cardiovascular system are rare and include pericarditis, fulminant myocarditis with a fast, slow, or irregular heartbeat , and exacerbation of pre-existing cardiovascular disease. Inflammation or swelling of muscles accompanied by muscle tissue breaking down occurs rarely, usually in children, which presents as extreme tenderness and muscle pain in the legs and a reluctance to walk for 2–3 days. Influenza can affect pregnancy, including causing smaller neonatal size, increased risk of premature birth, and an increased risk of child death shortly before or after birth. Neurological complications have been associated with influenza on rare occasions, including aseptic meningitis, encephalitis, disseminated encephalomyelitis, transverse myelitis, and Guillain–Barré syndrome . Additionally, febrile seizures and Reye syndrome can occur, most commonly in children. Influenza-associated encephalopathy can occur directly from central nervous system infection from the presence of the virus in blood and presents as sudden onset of fever with convulsions, followed by rapid progression to coma. An atypical form of encephalitis called encephalitis lethargica, characterized by headache, drowsiness, and coma, may rarely occur sometime after infection. In survivors of influenza-associated encephalopathy, neurological defects may occur. Primarily in children, in severe cases the immune system may rarely dramatically overproduce white blood cells that release cytokines, causing severe inflammation. People who are at least 65 years of age, due to a weakened immune system from aging or a chronic illness, are a high-risk group for developing complications, as are children less than one year of age and children who have not been previously exposed to influenza viruses multiple times. Pregnant women are at an elevated risk, which increases by trimester and lasts up to two weeks after childbirth. Obesity, in particular a body mass index greater than 35–40, is associated with greater amounts of viral replication, increased severity of secondary bacterial infection, and reduced vaccination efficacy. People who have underlying health conditions are also considered at-risk, including those who have congenital or chronic heart problems or lung (e.g. asthma), kidney, liver, blood, neurological, or metabolic (e.g. diabetes ) disorders, as are people who are immunocompromised from chemotherapy, asplenia , prolonged steroid treatment, splenic dysfunction, or HIV infection. Tobacco use, including past use, places a person at risk. The role of genetics in influenza is not well researched, but it may be a factor in influenza mortality. Influenza is typically characterized by seasonal epidemics and sporadic pandemics. Most of the burden of influenza is a result of flu seasons caused by IAV and IBV. Among IAV subtypes, H1N1 and H3N2 circulate in humans and are responsible for seasonal influenza. Cases disproportionately occur in children, but most severe causes are among the elderly, the very young, and the immunocompromised. In a typical year, influenza viruses infect 5–15% of the global population, causing 3–5 million cases of severe illness annually and accounting for 290,000–650,000 deaths each year due to respiratory illness. 5–10% of adults and 20–30% of children contract influenza each year. The reported number of influenza cases is usually much lower than the actual number of cases. During seasonal epidemics, it is estimated that about 80% of otherwise healthy people who have a cough or sore throat have the flu. Approximately 30–40% of people hospitalized for influenza develop pneumonia, and about 5% of all severe pneumonia cases in hospitals are due to influenza, which is also the most common cause of ARDS in adults. In children, influenza is one of the two most common causes of ARDS, the other being the respiratory syncytial virus . About 3–5% of children each year develop otitis media due to influenza. Adults who develop organ failure from influenza and children who have PIM scores and acute renal failure have higher rates of mortality. During seasonal influenza, mortality is concentrated in the very young and the elderly, whereas during flu pandemics, young adults are often affected at a high rate. In temperate regions, the number of influenza cases varies from season to season. Lower vitamin D levels, presumably due to less sunlight, lower humidity, lower temperature, and minor changes in virus proteins caused by antigenic drift contribute to annual epidemics that peak during the winter season. In the northern hemisphere, this is from October to May (more narrowly December to April ), and in the southern hemisphere, this is from May to October (more narrowly June to September ). There are therefore two distinct influenza seasons every year in temperate regions, one in the northern hemisphere and one in the southern hemisphere. In tropical and subtropical regions, seasonality is more complex and appears to be affected by various climatic factors such as minimum temperature, hours of sunshine, maximum rainfall, and high humidity. Influenza may therefore occur year-round in these regions. Influenza epidemics in modern times have the tendency to start in the eastern or southern hemisphere, with Asia being a key reservoir of influenza viruses. IAV and IBV co-circulate, so the two have the same patterns of transmission. The seasonality of ICV, however, is poorly understood. ICV infection is most common in children under the age of two, and by adulthood most people have been exposed to it. ICV-associated hospitalization most commonly occurs in children under the age of three and is frequently accompanied by co-infection with another virus or a bacterium, which may increase the severity of disease. When considering all hospitalizations for respiratory illness among young children, ICV appears to account for only a small percentage of such cases. Large outbreaks of ICV infection can occur, so incidence varies significantly. Outbreaks of influenza caused by novel influenza viruses are common. Depending on the level of pre-existing immunity in the population, novel influenza viruses can spread rapidly and cause pandemics with millions of deaths. These pandemics, in contrast to seasonal influenza, are caused by antigenic shifts involving animal influenza viruses. To date, all known flu pandemics have been caused by IAVs, and they follow the same pattern of spreading from an origin point to the rest of the world over the course of multiple waves in a year. Pandemic strains tend to be associated with higher rates of pneumonia in otherwise healthy individuals. Generally after each influenza pandemic, the pandemic strain continues to circulate as the cause of seasonal influenza, replacing prior strains. From 1700 to 1889, influenza pandemics occurred about once every 50–60 years. Since then, pandemics have occurred about once every 10–50 years, so they may be getting more frequent over time. The first influenza epidemic may have occurred around 6,000 BC in China, and possible descriptions of influenza exist in Greek writings from the 5th century BC. In both 1173–1174 AD and 1387 AD, epidemics occurred across Europe that were named "influenza". Whether these epidemics or others were caused by influenza is unclear since there was then no consistent naming pattern for epidemic respiratory diseases, and "influenza" did not become clearly associated with respiratory disease until centuries later. Influenza may have been brought to the Americas as early as 1493, when an epidemic disease resembling influenza killed most of the population of the Antilles . The first convincing record of an influenza pandemic was in 1510 . It began in East Asia before spreading to North Africa and then Europe. Following the pandemic, seasonal influenza occurred, with subsequent pandemics in 1557 and 1580. The flu pandemic in 1557 was potentially the first time influenza was connected to miscarriage and death of pregnant women. The 1580 influenza pandemic originated in Asia during summer, spread to Africa, then Europe, and finally America. By the end of the 16th century, influenza was beginning to become understood as a specific, recognizable disease with epidemic and endemic forms. In 1648, it was discovered that horses also experience influenza. Influenza data after 1700 is more accurate, so it is easier to identify flu pandemics after this point. The first flu pandemic of the 18th century started in 1729 in Russia in spring, spreading worldwide over the course of three years with distinct waves, the later ones being more lethal. Another flu pandemic occurred in 1781–1782, starting in China in autumn. From this pandemic, influenza became associated with sudden outbreaks of febrile illness. The next flu pandemic was from 1830 to 1833, beginning in China in winter. This pandemic had a high attack rate, but the mortality rate was low. A minor influenza pandemic occurred from 1847 to 1851 at the same time as the third cholera pandemic and was the first flu pandemic to occur with vital statistics being recorded, so influenza mortality was clearly recorded for the first time. Highly pathogenic avian influenza was recognized in 1878 and was soon linked to transmission to humans. By the time of the 1889 pandemic , which may have been caused by an H2N2 strain, the flu had become an easily recognizable disease. The microbial agent responsible for influenza was incorrectly identified in 1892 by R. F. J. Pfeiffer as the bacteria species Haemophilus influenzae , which retains "influenza" in its name. From 1901 to 1903, Italian and Austrian researchers were able to show that avian influenza, then called "fowl plague", was caused by a microscopic agent smaller than bacteria by using filters with pores too small for bacteria to pass through. The fundamental differences between viruses and bacteria, however, were not yet fully understood. From 1918 to 1920, the Spanish flu pandemic became the most devastating influenza pandemic and one of the deadliest pandemics in history. The pandemic, probably caused by H1N1, likely began in the United States before spreading worldwide via soldiers during and after the First World War . The initial wave in the first half of 1918 was relatively minor and resembled past flu pandemics, but the second wave later that year had a much higher mortality rate. A third wave with lower mortality occurred in many places a few months after the second. By the end of 1920, it is estimated that about a third to half of all people in the world had been infected, with tens of millions of deaths, disproportionately young adults. During the 1918 pandemic, the respiratory route of transmission was clearly identified and influenza was shown to be caused by a "filter passer", not a bacterium, but there remained a lack of agreement about influenza's cause for another decade and research on influenza declined. After the pandemic, H1N1 circulated in humans in seasonal form until the next pandemic. In 1931, Richard Shope published three papers identifying a virus as the cause of swine influenza, a then newly recognized disease among pigs that was characterized during the second wave of the 1918 pandemic. Shope's research reinvigorated research on human influenza, and many advances in virology, serology, immunology, experimental animal models, vaccinology, and immunotherapy have since arisen from influenza research. Just two years after influenza viruses were discovered, in 1933, IAV was identified as the agent responsible for human influenza. Subtypes of IAV were discovered throughout the 1930s, and IBV was discovered in 1940. During the Second World War , the US government worked on developing inactivated vaccines for influenza, resulting in the first influenza vaccine being licensed in 1945 in the United States. ICV was discovered two years later in 1947. In 1955, avian influenza was confirmed to be caused by IAV. Four influenza pandemics have occurred since WWII. The first of these was the Asian flu from 1957 to 1958, caused by an H2N2 strain and beginning in China's Yunnan province. The number of deaths probably exceeded one million, mostly among the very young and very old. This was the first flu pandemic to occur in the presence of a global surveillance system and laboratories able to study the novel influenza virus. After the pandemic, H2N2 was the IAV subtype responsible for seasonal influenza. The first antiviral drug against influenza, amantadine , was approved in 1966, with additional antiviral drugs being used since the 1990s. In 1968, H3N2 was introduced into humans through a rearrangement between an avian H3N2 strain and an H2N2 strain that was circulating in humans. The novel H3N2 strain emerged in Hong Kong and spread worldwide, causing the Hong Kong flu pandemic, which resulted in 500,000–2,000,000 deaths. This was the first pandemic to spread significantly by air travel. H2N2 and H3N2 co-circulated after the pandemic until 1971 when H2N2 waned in prevalence and was completely replaced by H3N2. In 1977, H1N1 reemerged in humans, possibly after it was released from a freezer in a laboratory accident, and caused a pseudo-pandemic . This H1N1 strain was antigenically similar to the H1N1 strains that circulated prior to 1957. Since 1977, both H1N1 and H3N2 have circulated in humans as part of seasonal influenza. In 1980, the classification system used to subtype influenza viruses was introduced. At some point, IBV diverged into two strains, named the B/Victoria-like and B/Yamagata-like lineages, both of which have been circulating in humans since 1983. In 1996, HPAI H5N1 was detected in Guangdong , China and a year later emerged in poultry in Hong Kong, gradually spreading worldwide from there. A small H5N1 outbreak in humans in Hong Kong occurred then, and sporadic human cases have occurred since 1997, carrying a high case fatality rate. The most recent flu pandemic was the 2009 swine flu pandemic , which originated in Mexico and resulted in hundreds of thousands of deaths. It was caused by a novel H1N1 strain that was a reassortment of human, swine, and avian influenza viruses. The 2009 pandemic had the effect of replacing prior H1N1 strains in circulation with the novel strain but not any other influenza viruses. Consequently, H1N1, H3N2, and both IBV lineages have been in circulation in seasonal form since the 2009 pandemic. In 2011, IDV was discovered in pigs in Oklahoma, USA, and cattle were later identified as the primary reservoir of IDV. In the same year, avian H7N9 was detected in China and began to cause human infections in 2013, starting in Shanghai and Anhui and remaining mostly in China. HPAI H7N9 emerged sometime in 2016 and has occasionally infected humans incidentally. Other AIVs have less commonly infected humans since the 1990s, including H5N6 , H6N1 , H7N2-4, H7N7 , and H10N7-8, and HPAI H subtypes such as H5N1-3, H5N5-6, and H5N8 have begun to spread throughout much of the world since the 2010s. Future flu pandemics, which may be caused by an influenza virus of avian origin, are viewed as almost inevitable, and increased globalization has made it easier for novel viruses to spread, so there are continual efforts to prepare for future pandemics and improve the prevention and treatment of influenza. The word influenza comes from the Italian word influenza , from medieval Latin influentia , originally meaning 'visitation' or 'influence'. Terms such as influenza di freddo , meaning 'influence of the cold', and influenza di stelle , meaning 'influence of the stars' are attested from the 14th century. The latter referred to the disease's cause, which at the time was ascribed by some to unfavorable astrological conditions. As early as 1504, influenza began to mean a 'visitation' or 'outbreak' of any disease affecting many people in a single place at once. During an outbreak of influenza in 1743 that started in Italy and spread throughout Europe, the word reached the English language and was anglicized in pronunciation. Since the mid-1800s, influenza has also been used to refer to severe colds. The shortened form of the word, "flu", is first attested in 1839 as flue with the spelling flu confirmed in 1893. Other names that have been used for influenza include epidemic catarrh , la grippe from French , sweating sickness , and, especially when referring to the 1918 pandemic strain, Spanish fever . The word influenza comes from the Italian word influenza , from medieval Latin influentia , originally meaning 'visitation' or 'influence'. Terms such as influenza di freddo , meaning 'influence of the cold', and influenza di stelle , meaning 'influence of the stars' are attested from the 14th century. The latter referred to the disease's cause, which at the time was ascribed by some to unfavorable astrological conditions. As early as 1504, influenza began to mean a 'visitation' or 'outbreak' of any disease affecting many people in a single place at once. During an outbreak of influenza in 1743 that started in Italy and spread throughout Europe, the word reached the English language and was anglicized in pronunciation. Since the mid-1800s, influenza has also been used to refer to severe colds. The shortened form of the word, "flu", is first attested in 1839 as flue with the spelling flu confirmed in 1893. Other names that have been used for influenza include epidemic catarrh , la grippe from French , sweating sickness , and, especially when referring to the 1918 pandemic strain, Spanish fever . Influenza research includes efforts to understand how influenza viruses enter hosts, the relationship between influenza viruses and bacteria, how influenza symptoms progress, and why some influenza viruses are deadlier than others. Non-structural proteins encoded by influenza viruses are periodically discovered and their functions are continually under research. Past pandemics, and especially the 1918 pandemic, are the subject of much research to understand flu pandemics. As part of pandemic preparedness, the Global Influenza Surveillance and Response System is a global network of laboratories that monitors influenza transmission and epidemiology. Additional areas of research include ways to improve the diagnosis, treatment, and prevention of influenza. Existing diagnostic methods have a variety of limitations coupled with their advantages. For example, NATs have high sensitivity and specificity but are impractical in under-resourced regions due to their high cost, complexity, maintenance, and training required. Low-cost, portable RIDTs can rapidly diagnose influenza but have highly variable sensitivity and are unable to subtype IAV. As a result of these limitations and others, research into new diagnostic methods revolves around producing new methods that are cost-effective, less labor-intensive, and less complex than existing methods while also being able to differentiate influenza species and IAV subtypes. One approach in development are lab-on-a-chips , which are diagnostic devices that make use of a variety of diagnostic tests, such as RT-PCR and serological assays, in microchip form. These chips have many potential advantages, including high reaction efficiency, low energy consumption, and low waste generation. New antiviral drugs are also in development due to the elimination of adamantines as viable drugs and concerns over oseltamivir resistance. These include: NA inhibitors that can be injected intravenously, such as intravenous formulations of zanamivir; favipiravir , which is a polymerase inhibitor used against several RNA viruses; pimodivir , which prevents cap-binding required during viral transcription; and nitazoxanide , which inhibits HA maturation. Reducing excess inflammation in the respiratory tract is also subject to much research since this is one of the primary mechanisms of influenza pathology. Other forms of therapy in development include monoclonal and polyclonal antibodies that target viral proteins, convalescent plasma, different approaches to modify the host antiviral response, and stem cell -based therapies to repair lung damage. Much research on LAIVs focuses on identifying genome sequences that can be deleted to create harmless influenza viruses in vaccines that still confer immunity. The high variability and rapid evolution of influenza virus antigens, however, is a major obstacle in developing effective vaccines. Furthermore, it is hard to predict which strains will be in circulation during the next flu season, manufacturing a sufficient quantity of flu vaccines for the next season is difficult, LAIVs have limited efficacy, and repeated annual vaccination potentially has diminished efficacy. For these reasons, "broadly-reactive" or "universal" flu vaccines are being researched that can provide protection against many or all influenza viruses. Approaches to develop such a vaccine include HA stalk-based methods such as chimeras that have the same stalk but different heads, HA head-based methods such as computationally optimized broadly neutralizing antigens, anti-idiotypic antibodies , and vaccines to elicit immune responses to highly conserved viral proteins. mRNA vaccines to provide protection against influenza are also under research. In recent years, controversy emerged over the ethical justifications for certain 'gain-of-function' (GOF) studies on influenza. Aquatic birds such as ducks, geese, shorebirds, and gulls are the primary reservoir of IAVs. In birds, AIVs may be either low pathogenic avian influenza (LPAI) viruses that produce little to no symptoms or highly pathogenic avian influenza (HPAI) viruses that cause severe illness. Symptoms of HPAI infection include lack of energy and appetite, decreased egg production, soft-shelled or misshapen eggs, swelling of the head, comb, wattles, and hocks, purple discoloration of wattles, combs, and legs, nasal discharge, coughing, sneezing, incoordination, and diarrhea. Birds infected with an HPAI virus may also die suddenly without any signs of infection. The distinction between LPAI and HPAI can generally be made based on how lethal an AIV is to chickens. At the genetic level, an AIV can be usually be identified as an HPAI virus if it has a multibasic cleavage site in the HA protein, which contains additional residues in the HA gene. Most AIVs are LPAI. Notable HPAI viruses include HPAI H5N1 and HPAI H7N9. HPAI viruses have been a major disease burden in the 21st century, resulting in the death of large numbers of birds. In H7N9's case, some circulating strains were originally LPAI but became HPAI by acquiring the HA multibasic cleavage site. Avian H9N2 is also of concern because although it is LPAI, it is a common donor of genes to H5N1 and H7N9 during reassortment. Migratory birds can spread influenza across long distances. An example of this was when an H5N1 strain in 2005 infected birds at Qinghai Lake , China, which is a stopover and breeding site for many migratory birds, subsequently spreading the virus to more than 20 countries across Asia, Europe, and the Middle East. AIVs can be transmitted from wild birds to domestic free-range ducks and in turn to poultry through contaminated water, aerosols, and fomites. Ducks therefore act as key intermediates between wild and domestic birds. Transmission to poultry typically occurs in backyard farming and live animal markets where multiple species interact with each other. From there, AIVs can spread to poultry farms in the absence of adequate biosecurity. Among poultry, HPAI transmission occurs through aerosols and contaminated feces, cages, feed, and dead animals. Back-transmission of HPAI viruses from poultry to wild birds has occurred and is implicated in mass die-offs and intercontinental spread. AIVs have occasionally infected humans through aerosols, fomites, and contaminated water. Direction transmission from wild birds is rare. Instead, most transmission involves domestic poultry, mainly chickens, ducks, and geese but also a variety of other birds such as guinea fowl, partridge, pheasants, and quails. The primary risk factor for infection with AIVs is exposure to birds in farms and live poultry markets. Typically, infection with an AIV has an incubation period of 3–5 days but can be up to 9 days. H5N1 and H7N9 cause severe lower respiratory tract illness, whereas other AIVs such as H9N2 cause a more mild upper respiratory tract illness, commonly with conjunctivitis. Limited transmission of avian H2, H5-7, H9, and H10 subtypes from one person to another through respiratory droplets, aerosols, and fomites has occurred, but sustained human-to-human transmission of AIVs has not occurred. Before 2013, H5N1 was the most common AIV to infect humans. Since then, H7N9 has been responsible for most human cases. Influenza in pigs is a respiratory disease similar to influenza in humans and is found worldwide. Asymptomatic infections are common. Symptoms typically appear 1–3 days after infection and include fever, lethargy, anorexia, weight loss, labored breathing, coughing, sneezing, and nasal discharge. In sows, pregnancy may be aborted. Complications include secondary infections and potentially fatal bronchopneumonia . Pigs become contagious within a day of infection and typically spread the virus for 7–10 days, which can spread rapidly within a herd. Pigs usually recover from infection within 3–7 days after symptoms appear. Prevention and control measures include inactivated vaccines and culling infected herds. The influenza viruses usually responsible for swine flu are IAV subtypes H1N1, H1N2 , and H3N2. Some IAVs can be transmitted via aerosols from pigs to humans and vice versa. Furthermore, pigs, along with bats and quails, are recognized as a mixing vessel of influenza viruses because they have both α-2,3 and α-2,6 sialic acid receptors in their respiratory tract. Because of that, both avian and mammalian influenza viruses can infect pigs. If co-infection occurs, then reassortment is possible. A notable example of this was the reassortment of a swine, avian, and human influenza virus in 2009, resulting in a novel H1N1 strain that caused the 2009 flu pandemic. Spillover events from humans to pigs, however, appear to be more common than from pigs to humans. Influenza viruses have been found in many other animals, including cattle, horses, dogs, cats, and marine mammals. Nearly all IAVs are apparently descended from ancestral viruses in birds. The exception are bat influenza-like viruses, which have an uncertain origin. These bat viruses have HA and NA subtypes H17, H18, N10, and N11. H17N10 and H18N11 are unable to reassort with other IAVs, but they are still able to replicate in other mammals. AIVs sometimes crossover into mammals. For example, in late 2016 to early 2017, an avian H7N2 strain was found to be infecting cats in New York. Equine IAVs include H7N7 and two lineages of H3N8 . H7N7, however, has not been detected in horses since the late 1970s, so it may have become extinct in horses. H3N8 in equines spreads via aerosols and causes respiratory illness. Equine H3N8 perferentially binds to α-2,3 sialic acids, so horses are usually considered dead-end hosts, but transmission to dogs and camels has occurred, raising concerns that horses may be mixing vessels for reassortment. In canines, the only IAVs in circulation are equine-derived H3N8 and avian-derived H3N2. Canine H3N8 has not been observed to reassort with other subtypes. H3N2 has a much broader host range and can reassort with H1N1 and H5N1. An isolated case of H6N1 likely from a chicken was found infecting a dog, so other AIVs may emerge in canines. Other mammals to be infected by IAVs include H7N7 and H4N5 in seals, H1N3 in whales, and H10N4 and H3N2 in minks. Various mutations have been identified that are associated with AIVs adapting to mammals. Since HA proteins vary in which sialic acids they bind to, mutations in the HA receptor binding site can allow AIVs to infect mammals. Other mutations include mutations affecting which sialic acids NA proteins cleave and a mutation in the PB2 polymerase subunit that improves tolerance of lower temperatures in mammalian respiratory tracts and enhances RNP assembly by stabilizing NP and PB2 binding. IBV is mainly found in humans but has also been detected in pigs, dogs, horses, and seals. Likewise, ICV primarily infects humans but has been observed in pigs, dogs, cattle, and dromedary camels. IDV causes an influenza-like illness in pigs but its impact in its natural reservoir, cattle, is relatively unknown. It may cause respiratory disease resembling human influenza on its own, or it may be part of a bovine respiratory disease (BRD) complex with other pathogens during co-infection. BRD is a concern for the cattle industry, so IDV's possible involvement in BRD has led to research on vaccines for cattle that can provide protection against IDV. Two antigenic lineages are in circulation: D/swine/Oklahoma/1334/2011 (D/OK) and D/bovine/Oklahoma/660/2013 (D/660). Aquatic birds such as ducks, geese, shorebirds, and gulls are the primary reservoir of IAVs. In birds, AIVs may be either low pathogenic avian influenza (LPAI) viruses that produce little to no symptoms or highly pathogenic avian influenza (HPAI) viruses that cause severe illness. Symptoms of HPAI infection include lack of energy and appetite, decreased egg production, soft-shelled or misshapen eggs, swelling of the head, comb, wattles, and hocks, purple discoloration of wattles, combs, and legs, nasal discharge, coughing, sneezing, incoordination, and diarrhea. Birds infected with an HPAI virus may also die suddenly without any signs of infection. The distinction between LPAI and HPAI can generally be made based on how lethal an AIV is to chickens. At the genetic level, an AIV can be usually be identified as an HPAI virus if it has a multibasic cleavage site in the HA protein, which contains additional residues in the HA gene. Most AIVs are LPAI. Notable HPAI viruses include HPAI H5N1 and HPAI H7N9. HPAI viruses have been a major disease burden in the 21st century, resulting in the death of large numbers of birds. In H7N9's case, some circulating strains were originally LPAI but became HPAI by acquiring the HA multibasic cleavage site. Avian H9N2 is also of concern because although it is LPAI, it is a common donor of genes to H5N1 and H7N9 during reassortment. Migratory birds can spread influenza across long distances. An example of this was when an H5N1 strain in 2005 infected birds at Qinghai Lake , China, which is a stopover and breeding site for many migratory birds, subsequently spreading the virus to more than 20 countries across Asia, Europe, and the Middle East. AIVs can be transmitted from wild birds to domestic free-range ducks and in turn to poultry through contaminated water, aerosols, and fomites. Ducks therefore act as key intermediates between wild and domestic birds. Transmission to poultry typically occurs in backyard farming and live animal markets where multiple species interact with each other. From there, AIVs can spread to poultry farms in the absence of adequate biosecurity. Among poultry, HPAI transmission occurs through aerosols and contaminated feces, cages, feed, and dead animals. Back-transmission of HPAI viruses from poultry to wild birds has occurred and is implicated in mass die-offs and intercontinental spread. AIVs have occasionally infected humans through aerosols, fomites, and contaminated water. Direction transmission from wild birds is rare. Instead, most transmission involves domestic poultry, mainly chickens, ducks, and geese but also a variety of other birds such as guinea fowl, partridge, pheasants, and quails. The primary risk factor for infection with AIVs is exposure to birds in farms and live poultry markets. Typically, infection with an AIV has an incubation period of 3–5 days but can be up to 9 days. H5N1 and H7N9 cause severe lower respiratory tract illness, whereas other AIVs such as H9N2 cause a more mild upper respiratory tract illness, commonly with conjunctivitis. Limited transmission of avian H2, H5-7, H9, and H10 subtypes from one person to another through respiratory droplets, aerosols, and fomites has occurred, but sustained human-to-human transmission of AIVs has not occurred. Before 2013, H5N1 was the most common AIV to infect humans. Since then, H7N9 has been responsible for most human cases. Influenza in pigs is a respiratory disease similar to influenza in humans and is found worldwide. Asymptomatic infections are common. Symptoms typically appear 1–3 days after infection and include fever, lethargy, anorexia, weight loss, labored breathing, coughing, sneezing, and nasal discharge. In sows, pregnancy may be aborted. Complications include secondary infections and potentially fatal bronchopneumonia . Pigs become contagious within a day of infection and typically spread the virus for 7–10 days, which can spread rapidly within a herd. Pigs usually recover from infection within 3–7 days after symptoms appear. Prevention and control measures include inactivated vaccines and culling infected herds. The influenza viruses usually responsible for swine flu are IAV subtypes H1N1, H1N2 , and H3N2. Some IAVs can be transmitted via aerosols from pigs to humans and vice versa. Furthermore, pigs, along with bats and quails, are recognized as a mixing vessel of influenza viruses because they have both α-2,3 and α-2,6 sialic acid receptors in their respiratory tract. Because of that, both avian and mammalian influenza viruses can infect pigs. If co-infection occurs, then reassortment is possible. A notable example of this was the reassortment of a swine, avian, and human influenza virus in 2009, resulting in a novel H1N1 strain that caused the 2009 flu pandemic. Spillover events from humans to pigs, however, appear to be more common than from pigs to humans. Influenza viruses have been found in many other animals, including cattle, horses, dogs, cats, and marine mammals. Nearly all IAVs are apparently descended from ancestral viruses in birds. The exception are bat influenza-like viruses, which have an uncertain origin. These bat viruses have HA and NA subtypes H17, H18, N10, and N11. H17N10 and H18N11 are unable to reassort with other IAVs, but they are still able to replicate in other mammals. AIVs sometimes crossover into mammals. For example, in late 2016 to early 2017, an avian H7N2 strain was found to be infecting cats in New York. Equine IAVs include H7N7 and two lineages of H3N8 . H7N7, however, has not been detected in horses since the late 1970s, so it may have become extinct in horses. H3N8 in equines spreads via aerosols and causes respiratory illness. Equine H3N8 perferentially binds to α-2,3 sialic acids, so horses are usually considered dead-end hosts, but transmission to dogs and camels has occurred, raising concerns that horses may be mixing vessels for reassortment. In canines, the only IAVs in circulation are equine-derived H3N8 and avian-derived H3N2. Canine H3N8 has not been observed to reassort with other subtypes. H3N2 has a much broader host range and can reassort with H1N1 and H5N1. An isolated case of H6N1 likely from a chicken was found infecting a dog, so other AIVs may emerge in canines. Other mammals to be infected by IAVs include H7N7 and H4N5 in seals, H1N3 in whales, and H10N4 and H3N2 in minks. Various mutations have been identified that are associated with AIVs adapting to mammals. Since HA proteins vary in which sialic acids they bind to, mutations in the HA receptor binding site can allow AIVs to infect mammals. Other mutations include mutations affecting which sialic acids NA proteins cleave and a mutation in the PB2 polymerase subunit that improves tolerance of lower temperatures in mammalian respiratory tracts and enhances RNP assembly by stabilizing NP and PB2 binding. IBV is mainly found in humans but has also been detected in pigs, dogs, horses, and seals. Likewise, ICV primarily infects humans but has been observed in pigs, dogs, cattle, and dromedary camels. IDV causes an influenza-like illness in pigs but its impact in its natural reservoir, cattle, is relatively unknown. It may cause respiratory disease resembling human influenza on its own, or it may be part of a bovine respiratory disease (BRD) complex with other pathogens during co-infection. BRD is a concern for the cattle industry, so IDV's possible involvement in BRD has led to research on vaccines for cattle that can provide protection against IDV. Two antigenic lineages are in circulation: D/swine/Oklahoma/1334/2011 (D/OK) and D/bovine/Oklahoma/660/2013 (D/660).

Wiki

Pandemic influenza

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1957–1958 influenza pandemic

The 1957–1958 Asian flu pandemic was a global pandemic of influenza A virus subtype H2N2 that originated in Guizhou in Southern China . The number of excess deaths caused by the pandemic is estimated to be 1–4 million around the world (1957–1958 and probably beyond), making it one of the deadliest pandemics in history. A decade later, a reassorted viral strain H3N2 further caused the Hong Kong flu pandemic (1968–1969). The first cases were reported in Guizhou of southern China , in 1956 or in early 1957. Observers within China noted an epidemic beginning in the third week of February in western Guizhou, between its capital Guiyang and the city of Qujing in neighbouring Yunnan province. They were soon reported in Yunnan in late February or early March 1957. By the middle of March, the flu had spread all over China. The People's Republic of China was not a member of the World Health Organization at the time (not until 1981 ), and did not inform other countries about the outbreak. The United States CDC , however, contradicting most records, states that the flu was "first reported in Singapore in February 1957". In late 1957, a second wave of the flu took place in Northern China , especially in rural areas. In the same year, as response to the epidemic, the Chinese government established the Chinese National Influenza Center (CNIC) , which soon published a manual on influenza in 1958. On 17 April 1957, The Times reported that "an influenza epidemic has affected thousands of Hong Kong residents". The same day The New York Times reported that local press estimated at least 250,000 persons were receiving treatment by that time, out of the colony's total population of about 2.5 million. The recent influx of about 700,000 refugees from mainland China had intensified authorities' fears of epidemics and fires due to crowded conditions, and according to a report received by the US Influenza Information Center on 3 May, the disease was said to be occurring mainly among these refugees. By the end of the month (or as early as February ), Singapore also experienced an outbreak of the new flu, which peaked in mid-May with 680 deaths. The only National Influenza Center reporting data to the World Health Organization for the southeast-Asian region in 1957 was located in Singapore, and thus the country was the first to notify the WHO on 4 May about an extensive outbreak of the flu which "appeared to have been introduced from Hong Kong". By the end of May, the outbreak had spread across Mainland Southeast Asia and also involved Indonesia , the Philippines , and Japan . In Taiwan , 100,000 were affected by mid-May. India suffered a million cases by June. In late June, the pandemic reached the United Kingdom . By June 1957, it reached the United States , where it initially caused few infections. Some of the first people affected were US Navy personnel at destroyers docked at Newport Naval Station and new military recruits elsewhere. The first wave peaked in October and affected mainly children who recently returned to school after summer break. The second wave, in January and February 1958, was more pronounced among elderly people and so was more fatal. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. The 1957–1958 pandemic was the first influenza pandemic to occur since the creation of the World Health Organization in 1947. Memories of the 1918 pandemic were still ever-present. In recognition of the worldwide threat of epidemic influenza, the WHO launched its Global Influenza Programme in 1947 with the establishment of the World Influenza Centre at the National Institute for Medical Research in London . This eventually gave rise to the Global Influenza Surveillance Network in 1952 to facilitate global scientific collaboration and fulfil the objectives of the programme. In 1957, China was not a member of the WHO, and thus it was not a part of its influenza surveillance network. Therefore, it took several weeks, if not months, for the news of an outbreak to reach the WHO, when the virus had already spread into Hong Kong and then to Singapore. This fact would be lamented repeatedly after the pandemic, and it was taken as reinforcement of the importance of a "truly worldwide" network of epidemiological surveillance. Following this delay, things then "moved swiftly". After receiving the report out of Singapore in early May, the WHO reported on the developing outbreak for the first time in its Weekly Epidemiological Record published on 10 May. Within three weeks laboratories around the world had concluded that the cause of these epidemics was a new variant of influenza A. This information was first reported in the Weekly Epidemiological Record for 29 May. On 14 June, the WHO declared that attempts at large-scale quarantine were "as costly as they are ineffective", instead recommending only that acute cases be isolated. It reiterated that all reports it had received emphasized the mildness of the disease in most cases, with the very few deaths having occurred mainly in elderly victims suffering from chronic bronchitis. The need for a single, consistent name for the novel virus became clear as it continued to spread and became more commonly discussed. Up to this point, the causative agent had mostly been called "Far East influenza virus" or "Far East strain (influenza virus)" or even "Oriental flu", though "Asian influenza" had been used before. On 11 July, the question was finally taken up at an informal meeting of scientists during the Fourth International Poliomyelitis Congress in Geneva. There it was agreed that "Asian influenza" was a "descriptive and appropriate" name for the "contemporary manifestation of the ancient disease", as the term "Far East" was considered "not exact as to geographical location". On 23 July, the WHO issued a circular letter advising that surplus vaccine be made available to poorer countries at the "lowest economic price". On 16 August, William J. Tepsix, commander of Pennsylvania 's Veterans of Foreign Wars in the United States, sent a letter to United Nations Secretary-General Dag Hammarskjold demanding an investigation into whether the virus had been released by the Soviet Union or China. It is not clear if the UN or the WHO ever responded to Tepsix's letter. However, US Surgeon General Leroy E. Burney would later dismiss this notion on 26 August in response to a similar question raised by the press. On 11 October, the WHO announced that the virus had spread to all populated parts of the world aside from "a few islands or territories having no contact with the outside world". Following the main phase of the pandemic in 1957, the WHO reflected on its performance as part of its review of the first ten years of the organization in 1958. It concluded that "the WHO influenza programme fulfilled the major task allotted to it", which allowed "many parts of the world to organize health services to meet the threat and for some countries to attempt to protect priority groups by vaccination". However, it acknowledged that had its influenza surveillance network been "truly worldwide", as it would repeatedly lament it was not, then preparations could have begun two months earlier. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. The number of deaths peaked the week ending 17 October, with 600 reported in England and Wales . The vaccine was available in the same month in the United Kingdom. Although it was initially available only in limited quantities, its rapid deployment helped contain the pandemic. Hilleman's vaccine is believed to have saved hundreds of thousands of lives. Some predicted that the U.S. death toll would have reached 1 million without the vaccine that Hilleman called for. H2N2 influenza virus continued to be transmitted until 1968, when it transformed via antigenic shift into influenza A virus subtype H3N2 , the cause of the 1968 influenza pandemic . The first cases were reported in Guizhou of southern China , in 1956 or in early 1957. Observers within China noted an epidemic beginning in the third week of February in western Guizhou, between its capital Guiyang and the city of Qujing in neighbouring Yunnan province. They were soon reported in Yunnan in late February or early March 1957. By the middle of March, the flu had spread all over China. The People's Republic of China was not a member of the World Health Organization at the time (not until 1981 ), and did not inform other countries about the outbreak. The United States CDC , however, contradicting most records, states that the flu was "first reported in Singapore in February 1957". In late 1957, a second wave of the flu took place in Northern China , especially in rural areas. In the same year, as response to the epidemic, the Chinese government established the Chinese National Influenza Center (CNIC) , which soon published a manual on influenza in 1958. On 17 April 1957, The Times reported that "an influenza epidemic has affected thousands of Hong Kong residents". The same day The New York Times reported that local press estimated at least 250,000 persons were receiving treatment by that time, out of the colony's total population of about 2.5 million. The recent influx of about 700,000 refugees from mainland China had intensified authorities' fears of epidemics and fires due to crowded conditions, and according to a report received by the US Influenza Information Center on 3 May, the disease was said to be occurring mainly among these refugees. By the end of the month (or as early as February ), Singapore also experienced an outbreak of the new flu, which peaked in mid-May with 680 deaths. The only National Influenza Center reporting data to the World Health Organization for the southeast-Asian region in 1957 was located in Singapore, and thus the country was the first to notify the WHO on 4 May about an extensive outbreak of the flu which "appeared to have been introduced from Hong Kong". By the end of May, the outbreak had spread across Mainland Southeast Asia and also involved Indonesia , the Philippines , and Japan . In Taiwan , 100,000 were affected by mid-May. India suffered a million cases by June. In late June, the pandemic reached the United Kingdom . By June 1957, it reached the United States , where it initially caused few infections. Some of the first people affected were US Navy personnel at destroyers docked at Newport Naval Station and new military recruits elsewhere. The first wave peaked in October and affected mainly children who recently returned to school after summer break. The second wave, in January and February 1958, was more pronounced among elderly people and so was more fatal. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ] The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Since the 1918 pandemic , epidemiological infrastructure in the US had expanded considerably. The Armed Forces Epidemiological Board and its Commission on Influenza were established in 1941, marking the beginning of the Armed Forces' involvement in the control of influenza. Among other activities, the Board maintained surveillance of influenza-like illness around the world, operating 176 stations by 1957. The Commission on Influenza also conducted studies into vaccination, which was considered "the only really effective control measure available in combating influenza". The Communicable Disease Center (today the Centers for Disease Control and Prevention ) was formed in 1946 initially for the control of malaria within military installations in the southeastern US . In light of developing Cold War –era concerns over biological warfare , the Epidemic Intelligence Service was created in 1951 at the CDC as a combined service and training program in the field of applied epidemiology, with the purpose of investigating certain disease outbreaks, among other activities. The 1950s were a tumultuous time in public health in the US. After the incidence of poliomyelitis in the US reached a peak in 1952, the first vaccine against it was licensed in 1955. Its rollout that year was marred by an incident in April involving Cutter Laboratories , one of the manufacturers of the inactivated vaccine, in which some lots of its vaccine actually contained live virus, resulting in tens of thousands of vaccine-derived infections and tens of cases of paralytic polio. Oveta Culp Hobby , the first secretary of the Department of Health, Education, and Welfare , quit in July (though she claimed that her intention to resign went back to January and was so that she could care for her ailing husband, former Governor of Texas William P. Hobby ). Marion B. Folsom replaced her on 1 August. This vaccine incident reportedly strained the relationship between Hobby and the Surgeon General , Leonard A. Scheele . Hobby relegated the entirety of federal responsibility in the vaccine program to the Surgeon General, not the Secretary of Health, Education, and Welfare. After being sworn in for a third term in April 1956, with no public indication of his intentions, Scheele resigned on 1 August to work at a pharmaceutical company. On 8 August, his successor, Leroy E. Burney , was sworn in as the eighth Surgeon General. On 20 January 1957, Dwight D. Eisenhower and Richard Nixon were sworn in for a second term as president and vice president respectively. [ citation needed ]The notion that an influenza pandemic was developing in the Far East first occurred to American microbiologist Maurice Hilleman , who was alarmed by pictures of those affected by the virus in Hong Kong that were published in The New York Times , on 17 April 1957. Hilleman was then head of the Department of Respiratory Diseases at the Walter Reed Army Institute of Research . He immediately sent for virus samples from patients in the Far East, and, on 12 May, the first isolate was sent out to the vaccine manufacturers as soon as they all arrived in the US. The Office of the Surgeon General became aware of the situation in Asia on 20 May. Burney was out of the country at the time, representing the US at the Tenth World Health Assembly in Geneva . The Deputy Surgeon General, W.P. Dearing, spread the word and established special liaison with the National Institutes of Health on Burney's behalf. On 22 May, after working "around the clock" for the last five days, Hilleman's team reported that the viruses isolated in the Far East were type A but antigenically quite distinct from previously known strains. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The microbiologist was thereafter instrumental in stimulating the development of the pandemic vaccine. The day after Hilleman's announcement, the Division of Foreign Quarantine began to monitor travelers from the Far East for signs of respiratory illness. All Epidemic Intelligence Service officers and all relevant personnel at the CDC were alerted of the priority of investigating cases and outbreaks of influenza-like disease at that time. The Public Health Service formally began its participation in the national effort against the flu on 28 May. The Surgeons General of the military called a meeting with the Service to discuss the control of the novel influenza. The disease was noted for its mild presentation though high rates of attack in various settings. It was the opinion of those at the meeting that the virus was already in the US, but no epidemic was expected until the fall. It was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, the director of the National Institutes of Health, Justin M. Andrews , having consulted with CDC Director Robert J. Anderson , submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed, that state epidemiologists be alerted to watch for outbreaks of influenza-like illness, that EIS officers immediately investigate any reported outbreak, and that "the role of influenza vaccine as a public health measure be carefully studied...". On 31 May, Dearing reflected on the 1918 pandemic and how new strains of influenza emerge, "presumably by mutation", which may spark another pandemic at any time. In writing, he indicated his support for a mass immunization program, saying that, if epidemiologists did find the present situation "unusual or almost unique", then the burden of proof would shift to opponents of such a program. He asked the principal staff officers to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. The 1957–1958 pandemic was the first influenza pandemic to occur since the creation of the World Health Organization in 1947. Memories of the 1918 pandemic were still ever-present. In recognition of the worldwide threat of epidemic influenza, the WHO launched its Global Influenza Programme in 1947 with the establishment of the World Influenza Centre at the National Institute for Medical Research in London . This eventually gave rise to the Global Influenza Surveillance Network in 1952 to facilitate global scientific collaboration and fulfil the objectives of the programme. In 1957, China was not a member of the WHO, and thus it was not a part of its influenza surveillance network. Therefore, it took several weeks, if not months, for the news of an outbreak to reach the WHO, when the virus had already spread into Hong Kong and then to Singapore. This fact would be lamented repeatedly after the pandemic, and it was taken as reinforcement of the importance of a "truly worldwide" network of epidemiological surveillance. Following this delay, things then "moved swiftly". After receiving the report out of Singapore in early May, the WHO reported on the developing outbreak for the first time in its Weekly Epidemiological Record published on 10 May. Within three weeks laboratories around the world had concluded that the cause of these epidemics was a new variant of influenza A. This information was first reported in the Weekly Epidemiological Record for 29 May. On 14 June, the WHO declared that attempts at large-scale quarantine were "as costly as they are ineffective", instead recommending only that acute cases be isolated. It reiterated that all reports it had received emphasized the mildness of the disease in most cases, with the very few deaths having occurred mainly in elderly victims suffering from chronic bronchitis. The need for a single, consistent name for the novel virus became clear as it continued to spread and became more commonly discussed. Up to this point, the causative agent had mostly been called "Far East influenza virus" or "Far East strain (influenza virus)" or even "Oriental flu", though "Asian influenza" had been used before. On 11 July, the question was finally taken up at an informal meeting of scientists during the Fourth International Poliomyelitis Congress in Geneva. There it was agreed that "Asian influenza" was a "descriptive and appropriate" name for the "contemporary manifestation of the ancient disease", as the term "Far East" was considered "not exact as to geographical location". On 23 July, the WHO issued a circular letter advising that surplus vaccine be made available to poorer countries at the "lowest economic price". On 16 August, William J. Tepsix, commander of Pennsylvania 's Veterans of Foreign Wars in the United States, sent a letter to United Nations Secretary-General Dag Hammarskjold demanding an investigation into whether the virus had been released by the Soviet Union or China. It is not clear if the UN or the WHO ever responded to Tepsix's letter. However, US Surgeon General Leroy E. Burney would later dismiss this notion on 26 August in response to a similar question raised by the press. On 11 October, the WHO announced that the virus had spread to all populated parts of the world aside from "a few islands or territories having no contact with the outside world". Following the main phase of the pandemic in 1957, the WHO reflected on its performance as part of its review of the first ten years of the organization in 1958. It concluded that "the WHO influenza programme fulfilled the major task allotted to it", which allowed "many parts of the world to organize health services to meet the threat and for some countries to attempt to protect priority groups by vaccination". However, it acknowledged that had its influenza surveillance network been "truly worldwide", as it would repeatedly lament it was not, then preparations could have begun two months earlier. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. In December 1942, Dr. Thomas Francis Jr. , and his colleagues on the United States Armed Forces' Commission on Influenza (including Jonas Salk , future developer of the inactivated polio vaccine) began a series of key studies into the use of inactivated influenza virus vaccines, which for the first time demonstrated the protective effect of such vaccines against infection. Similar studies into their efficacy and safety continued until 1945, when the first inactivated virus vaccine entered the market for commercial use. In the fall of that year and the spring of 1946, the entirety of the Armed Forces received the inactivated virus vaccine. During the winter of 1946–1947, a worldwide influenza epidemic occurred, an event that for some time was itself considered a pandemic due to its global distribution albeit low mortality. Vaccines that had been effective during the 1943–1944 and 1944–1945 seasons suddenly failed during this epidemic. It was found that the influenza A virus had undergone significant antigenic drift , resulting in a virus that was quite antigenically distinct, but not one of an entirely new subtype. This experience demonstrated the necessity to alter vaccine composition to match newly circulating strains. In the winter of 1950–1951, a severe influenza epidemic ravaged England and Wales , the number of weekly deaths at one point even surpassing that of the 1918 pandemic in Liverpool . Public health experts in the US, fearing the implications of the outbreak on their country, decided to impose a challenge on themselves: to see how quickly the British virus could be imported into the US, its antigenic structure analyzed, and then incorporated into a new vaccine, if the virus were found to be distinct from preexisting strains. Upon receipt of the strains at the laboratories at Walter Reed Army Institute of Research and the National Institute of Allergy and Infectious Diseases , which then sent samples to the vaccine manufacturers, the two government laboratories were able to produce the required 1 liter of vaccine of "acceptable potency, sterility, and safety" in three weeks; the manufacturers were soon to follow. The exercise was considered a success by those involved, but it was recognized that a repeat performance in the future might not be so likely without the same factors in their favor. Out of this exercise came a list of recommended priority groups from the civilian occupational population to be inoculated in the event of an emergency. In 1954, the Armed Forces initiated routine annual vaccination against the flu, considered the "only really effective measure available in combating" the virus, but the Public Health Service did not recommend a comparable regimen to the general public. This was based on the relatively short-lived demonstrated immunity of the vaccines and the lack of certainty that the strains used in the polyvalent vaccines then would be the cause of epidemics in the future. However, this policy would be reexamined in light of the pandemic three years later. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. After reading of the epidemic underway in Hong Kong, Maurice Hilleman immediately sent for samples of the virus from patients in the Far East, which were collected in late April 1957 and received at the Walter Reed Army Institute of Research before the middle of May. The Division of Biologics Standards of the US Public Health Service released the first of the virus cultures, designated A/Jap/305/57, to vaccine manufacturers on 12 May 1957. An immediate issue encountered with the new variant was in choosing the isolate optimally adaptable to producing necessary virus growth in chick embryos. After study of the five isolates in total, it was concluded that none in particular would be chosen for production, but each manufacturer would use whichever isolate showed the best growth characteristics. Hilleman's team reported its finding of the antigenic novelty of the virus on 22 May after working "around the clock" for the last five days. Hilleman predicted an epidemic would strike the US when schools reopened in the fall. The Public Health Service formally began its participation in the effort against the flu on 29 May with a meeting with the Surgeons General of the military. The nature of the disease was discussed, and it was recommended that the Department of Defense purchase about 3 million doses of monovalent vaccine targeting the pandemic virus. The Commission on Influenza was asked to propose the composition of the polyvalent vaccine to be used as well. The following day, Justin M. Andrews, Director of NIH, having consulted with CDC Director Robert J. Anderson, submitted a memo that recommended, among other items, that the monovalent pandemic vaccine needed for the Department of Defense be licensed. On the last day of May, reflecting upon the experience of the 1918 pandemic, Acting Surgeon General W.P. Dearing indicated his support for a mass immunization program, if epidemiologists were to find the present situation "unusual or almost unique", in which case the burden of proof would shift to opponents of such a program. He asked the principal staff officers of the Office of the Surgeon General to explore whether "the investment of the few million dollars necessary" to organize an immunization campaign would be advisable, if the situation indeed justified it. Vaccine production was underway before the start of June. After receiving its samples on 23 May, for example, Merck Sharp & Dohme had produced "laboratory quantities" of pandemic vaccine within two weeks. Before the middle of June, the first experimental lots had been produced and promptly entered into testing at the National Institutes of Health, which was expected to take about two weeks. The first 90 volunteers from among PHS personnel were inoculated with the experimental vaccine on 18 June. On 5 June, the Assistant to the Surgeon General called a meeting with representatives of the three bureaus of the Service. The associate director of NIH reported that the technical problem in the production of the monovalent vaccine had been resolved and that it could be ready in September, with a polyvalent vaccine including the novel strain ready a month later. He advised that certain groups receive the monovalent vaccine at the same time as the Armed Forces, basing his priorities on the list produced following the 1951 exercise. It was made clear that this would not require any additional funding. The deputy chief of the Bureau of State Services then recommended that the Surgeon General form an advisory council of public health officials, physicians, and the manufacturers; his vision was one of the Public Health Service advocating for mass inoculation, which would necessitate extra funds. The first meeting of the Advisory Committee on Influenza occurred on 10 June. One general finding of this meeting was that since limited data suggested the existing polyvalent vaccine was not protective against the novel variant, an effective monovalent vaccine should be produced immediately. Existing polyvalent vaccine should be utilized as otherwise recommended. Furthermore, the present situation did not yet justify establishing priorities for civilian use or considering any federal subsidy in producing the vaccine. Following this meeting, Surgeon General Burney held a press conference, where he discussed the vaccine. He shared the Department of Defense's consideration of purchasing 4 million doses of the monovalent vaccine — enough to vaccinate the entire Armed Forces, estimated at 2.8 million. He made clear that production of the monovalent vaccine would occupy the manufacturers, and so they would not be able to produce both the monovalent and the polyvalent vaccines at the same time. He also shared the committee's recommendation that if only 4 million doses could be produced over the next six weeks, they should go to the Armed Forces. The second phase of the Public Health Service's Asian Influenza Program began with a meeting of technical representatives of the manufacturers with NIH on 12 June. The manufacturers were presented with the latest epidemiological information, including data on the virus isolates and their growth characteristics. Here each company's experience with the different strains used in production was also summarized, and they ultimately agreed to review their inventories and report a potential formula that would make best use of available materials. This same day, the State of New York announced its plan to start a pilot project to produce pandemic vaccine, authorized by Governor W. Averell Harriman . On 20 June, an associate director of NIH laid out various alternatives for the course of the virus in the US and how to respond to each: an explosive outbreak before 1 September, with either continued low mortality or increased virulence (vaccination would not be possible, except for the use of limited polyvalent vaccine supplies and possible use in 1958); sporadic local activity during the summer with an explosive outbreak in the winter, again with low mortality (vaccinate priority groups) or increased virulence (maximize vaccine production, vaccination would be required, and priority groups would receive it first); or sporadic local activity during the summer with normal incidence in the winter (no recommendation of vaccination). It was generally agreed that the most likely outcome would be closer to the second possibility, with sporadic local activity during the summer with an epidemic in the fall or winter, with little increase in lethality. It was also clear then that the quantities of vaccine necessary for large-scale inoculation would not be ready until after the middle of August, but if the epidemic held off until the fall and winter, as was considered likely, it would be possible protect a significant part of the population. This framework was later presented to the Secretary Folsom of Health, Education, and Welfare on 24 June. On 26 June, Burney met with representatives of the American Medical Association to discuss the virus and how best to employ medical manpower against a serious epidemic. The vaccination situation was also discussed, as well as the variety of federal responses envisioned by the Service. Although it was emphasized that the present situation did not appear to justify large-scale orders or subsidization of production by the federal government, the parties agreed up a partnership between the Public Health Service and the American Medical Association with the purpose of public health education. It was recognized that the public had heard much about the novel virus but had not heard a thing about how to protect itself against it. In 1957, six pharmaceutical companies were licensed to manufacture influenza vaccine: Merck Sharpe & Dohme, Eli Lilly & Co. , Parke, Davis & Co. , Pitman-Moore Co., National Drug Company, and Lederle Laboratories . As members of the pharmaceutical industry, they had participated in the effort since the day the Public Health Service sent them samples of the virus. Maurice Hilleman happened to be close to the industry, and he helped secure the initial involvement of the manufacturers, going to them directly to spur development and avoiding "the bureaucratic red tape" that might typically forestall manufacture of new pharmaceutical products. In the latter half of June, following a series of outbreaks of the novel virus aboard naval vessels docked on the East Coast, the Department of Defense provided a significant stimulus to commercial production by placing an order for 2,650,000 ml of monovalent vaccine. After Merck's production of "laboratory quantities" of vaccine by early June and the product's entry into clinical trials in the middle of June, initial batches from four other manufacturers, including Pitman-Moore Co. and Eli Lilly & Co., were sent to NIH in early July. By this time, Pitman-Moore had received a government contract for about half a million doses while Eli Lilly had not, though Lilly confirmed it would be moving ahead with production on a "preparedness basis". The Public Health Service announced the establishment of specifications in the manufacture of the pandemic vaccine, which were then sent to the manufacturers, on 10 July. Service officials that day also met with the executive committee of the Association of State and Territorial Health Officers in Washington, D.C. , where the flu situation was discussed. The officers agreed with the proposed PHS-AMA partnership to launch a public health education campaign, specifically one that urged vaccination against the flu. At this time, influenza vaccines had generally been used by large companies to protect their employees, but with the threat of a probable, large-scale outbreak, stimulating their broader use seemed advisable. With the middle of July came the need finally to make two key policy decisions: whether to recommend vaccination again the flu for the general public and whether to recommend to the manufacturers to continue production of the monovalent vaccine then intended only for military use or to recommend they shift to making a polyvalent vaccine incorporating the novel variant for use by the general public. As to the first question, such a recommendation was considered medically justified, but the necessary quantities of vaccine had never been produced so quickly. Beyond providing for its own employees and patients, PHS ruled out any purchasing of vaccine itself. To the end of ensuring adequate supply for the general public, Burney spoke to each of the manufacturers by telephone from 15 July through 19 July. They could see the need, "from the standpoint of public health", to vaccinate as much as one-third of the population, and given the predictions of an epidemic and the plans already being developed by public health officials, they agreed to make a sizable investment in vaccine production without any aid from the federal government. As to the second question, NIH believed that a polyvalent vaccine was preferable immunologically speaking, but the manufacturers were unsure they could produce large amounts of an effective polyvalent vaccine on the timeline envisioned. On the other hand, a monovalent vaccine would become preferable if the virus itself were to become significantly deadlier. Therefore, the wisest recommendation seemed to be for a monovalent vaccine for use by the general public once the needs of the Armed Forces had been satisfied. Burney ultimately made these decisions, but they were not necessarily set in stone. With the unpredictability of influenza well recognized, it was considered judicious to "hedge" any policy in favor of reducing a potential rise in mortality, were it to occur. The Division of Biologics Standards therefore outlined a set of facilities that could be used to shore up production if the situation worsened. A mandatory allocation system for distribution and appropriation of funds for the purchase of vaccine and for public vaccination clinics were considered feasible if circumstances ultimately justified them. The vaccine entered trials at Fort Ord on 26 July and Lowry Air Force Base on 29 July. At the beginning of August, PHS gave the go-ahead to the press to initiate its public health education campaign. Burney met with press to warn of "the very definite probability" of a widespread epidemic in the fall or winter. He shared that the manufacturers had agreed to working "triple shifts", every day of the week, to produce 8 million doses by the middle of September, of which half would go to the Armed Forces. The ultimate target was 60 million doses by 1 February. It was made clear that there would not be enough time to produce enough vaccine to inoculate a majority of the country before the flu season, but vaccination, as "the only known preventive" against the flu, was viewed as the best course of action. When asked about the potential for mass immunization programs like those against polio, Burney stated that these would be the states' responsibility, but he conceded that "you could probably get more immunized in a shorter period" that way. The principal reason against such a policy was, apparently, that "that isn't the ordinary way we do things in this country." On 2 August, representatives of the Armed Forces, the Veterans Administration , and PHS met to discuss the question of vaccine dosage. It was the opinion of the Office of the Surgeon General, upon review of studies thus far reported, that 1 cc (cubic centimeter) of monovalent vaccine, with a strength of 200 CCA units, would be "the most effective and practical dosage". This was five times the strength of the pilot vaccine initially announced on 10 July. This potency was selected in light of difficulties during the early-summer trials in obtaining high yields of the virus in embryonated eggs, with any strength greater than 200 CCA seeming unlikely. On 9 August, Burney recommended to the Office of the Surgeon General that export of the pandemic vaccine be controlled while supplies were limited. The next day, PHS announced its plans for a "nationwide battle" against the anticipated flu outbreak that fall and winter. Beginning in September, a mass education campaign would call for the public to get vaccinated through various media such as the press, radio, and television. On 12 August, Burney sent individual letters to each of the manufacturers requesting their cooperation with PHS in a "voluntary system of equitable interstate allocations" of the pandemic vaccine while supplies remained limited. They all agreed. This plan was later announced on 16 August, with the purpose of such a system being to ensure "an equitable availability of vaccine supplies throughout all parts of the country". The manufacturers were acknowledged as having "informally" shown a willingness to follow the system while vaccine remained scarce. In short, each state would receive shipments of a fraction of a lot of vaccine from each manufacturer equal to the proportion of that state's population to the population of the entire country. Burney emphasized that the Service "would not contemplate any allocation between public agency purchasers and commercial sales." The first lot of 502,000 doses of vaccines was released on 12 August. Almost immediately, issues with allocation became glaringly obvious. In Washington, D.C., physicians reported of an intensely worried public, asking more about the "Asiatic flu" than any other epidemic disease that any could recall. They feared that such pressure might bring about a black market around the vaccine (though Daniel L. Finucane, Director of the District Department of Health, doubted such a possibility). Nevertheless, Time reported that National Drug Co. and Lederle Laboratories had sent their initial doses to companies across the country, leaving it to them to distribute the shots, and that indeed individual doctors had begun vaccinating "favored patients". At the same time, the NFL 's Chicago Cardinals were able to announce that the entire team would be vaccinated against the flu. The pandemic vaccine became relevant for the Eisenhower administration not long after the first doses were released. White House Press Secretary James Hagerty would report that two doses had been sent to Secretary of the Interior Fred A. Seaton by PHS. However, Seaton decided beginning his inoculation was not necessary before his trip to Hawaii. On 21 August, a spokesperson for the Department of Agriculture had to deny the speculation that the use of millions of eggs necessary for vaccine production would "skyrocket" the price of eggs. That same day, President Eisenhower was asked whether he would receive the pandemic vaccine. He replied, "I am going to take it just as soon as ordinary people like I am can get it." Eisenhower later met with his chief economic advisor, Gabriel Hauge . On 22 August, Hauge was sent home ill. That same day, Burney stated that the president was "an essential person" and should get vaccinated immediately, a recommendation with which Eisenhower's personal physician, Major General Howard McCrum Snyder , "agreed completely". On 24 August, Burney made the pointed recommendation that those with a history of heart or lung conditions be vaccinated early. (Eisenhower had suffered a heart attack in September 1955.) Notably, he assured Snyder that there was sufficient vaccine in the district to cover this priority group. Finally, based on Burney's recommendation the preceding weekend, Eisenhower was vaccinated on 26 August, the injection administered by Snyder. Hagerty reported that all members of the White House who worked closely with the president would thereafter be vaccinated. That same week, the Association of State and Territorial Health Officers convened in Bethesda, Maryland , and Washington, D.C., beginning on 27 August for a two-day special meeting to discuss the pandemic response. Among other recommendations pertaining to preparing for a likely epidemic, the Committee on Vaccination Promotion outlined how such programs should be carried out and who should be prioritized for inoculation. The primary objective for any such program was considered "to prevent illness and death from epidemic influenza within the limits of available vaccine." The committee sided with PHS's informal agreement with the manufacturers that they participate in a "voluntary" system of interstate allocation. It was plainly acknowledged that "influenza vaccine is being manufactured and will becoming increasingly available but is not yet available for everyone"; therefore, PHS would recommend to civilian physicians that they prioritize those working in essential services maintaining the health of the community, those maintaining other basic services, and those considered to be at "special medical risk". It was stated that the pandemic vaccine had been approved for use in children as young as three months, with the following recommendations for administration: Children three months to five years of age would receive a two-dose regimen of 0.1 cc each, spaced over one to two weeks; children five to 12 years of age would receive a similar two-dose regimen but of 0.5 cc each; and children 13 years of age and older would receive the same dosage as for adults, a single, 1.0-cc injection. Finally, it was resolved that the two vaccination programs, that against polio and now that against influenza, "be continued as independent and parallel programs." The second lot of 562,610 doses was released on 28 August, bringing the total to 1,149,610 doses for both military and civilian use. Burney shared the expectation that, based on the current pace of production, it was possible that 80 to 85 million doses would be ready by 1 January, 20 million doses more and one month sooner than originally anticipated. The Armed Forces announced their intention to give two injections to each servicemember, and thus their order had increased from 4 million doses to over 7 million. Just as after release of the first batch of vaccine, issues with supply and allocation quickly became apparent yet again. Although authorities like the New York County Medical Society and wholesalers in Washington, D.C., made clear that vaccine would not be available for the public until September or even October, there was still intense demand for the vaccine. A physician's secretary in the district reported in The Evening Star that her office was receiving "dozens" of calls every day from anxious patients. This was not helped by Burney's statement days before, that there was sufficient vaccine in the district to vaccinate those with heart and lung conditions, such as the president. Even the State Department had not received any vaccine, and it was reportedly unknown when it would. Interestingly, in contrast to the D.C. situation, doctors in New York City reported that they had been asked about the vaccine, but the pressure was nowhere near that for the Salk polio vaccine when it had been in short supply. On 31 August, a spokesperson for National Drug stated that D.C. physicians had been "very well taken care of" with respect to vaccine. Finucane, the district health director, immediately pushed back on this claim, saying that he knew of "no large shipments of the vaccine into Washington" and that those who had received any were "lucky". Meanwhile, the pharmaceutical company had been very responsive to the demands of industrial concerns such as Bell Telephone , E. I. duPont de Nemours & Co., Inc. , and Pennsylvania Railroad . One district physician decried this state of affairs as "grossly unfair"; similarly, Dr. I. Phillips Frohman, a former chairman within the American Medical Association, labeled it "criminal". However, the company defended its distribution practices by asserting it was "trying to get as much of the vaccine out as possible." Ironically, The Star 's reporting on National Drug's statement regarding vaccine supply and Finucane's pushback, with the headline "Doctors Here Receive Vaccine for Patients", seemed to stimulate demand even more, according to physicians. J. Hunter Stewart, chief of the Information Office of the Office of the Surgeon General, clarified that there was no federal priority system beyond PHS's recommendations that the vaccine be distributed equitably and that it first go to healthcare providers. He emphasized: "But you must remember that these are recommendations." This insistence upon the voluntary nature of vaccine allocation was not satisfying to all. On 3 September, Dr. Thomas E. Mattingly wrote into The Star to thank it for debunking National Drug's statement and to discuss the situation in general. He described PHS's establishment of a system of priorities as "very wise" but asserted that it was "not enough to panic the public and not provide dependable discipline and guarantee a system of priorities". He called on the federal government to "accept both responsibility and purposeful leadership" and PHS to seize every last dose of vaccine and distribute it itself. The government would also reimburse the companies "for the fair cost of all vaccine they have been urged to manufacture." Others echoed this call for some "special action of one vague kind or another" by the federal government, just as had been advocated for during the early days of the Salk vaccine. On 4 September, PHS officially announced the system of allocation agreed to by the manufacturers, which would allocate vaccine supplies to states in proportion to their population, though it made clear that the program would not retroactively apply to any allotments of vaccine already shipped to fill military or civilian orders. The Service also emphatically reiterated that the allocation plan was "strictly voluntary". On 5 September, the week-long eighth session of the Regional Committee for the Western Pacific of the World Health Organization commenced in Hong Kong. Burney, the elected vice chairman for the session, gave a progress report on the pandemic response in the United States, including the vaccine situation, in which he stated his expectation that 85 million doses would be ready in order to combat the epidemic. That same day, PHS announced the release of a further 1,028,295 doses, entirely for civilian use, in addition to the 3,705,770 doses already released. As the vaccine began to be rolled out "in quantity", so too did the nationwide incidence of influenza begin to rise with the reopening of schools. On 18 September, PHS reported that vaccine production had fallen short of the original expectation of 8 million doses by the middle of the month, with only 5,430,442 having been released by that point. The release of another 1,526,590 doses that week, however, brought the total to 6,957,032. Despite this shortfall, the Service estimated that 12,200,000 doses would still be produced by the end of September. This goal proved feasible as production increased, and a total of 13,504,947 doses were ultimately released through 1 October. Although vaccine was, at this point, being rolled out at a faster pace than expected, the issue of exact allocation persisted. On 7 October, Time reported that most supplies had seemingly "been sold to anyone who went after [the vaccine] early and energetically"; this included, in particular, "football teams and business concerns." As a result, the San Francisco 49ers and the football teams of Stanford and the University of California had received inoculations, as had employees of Dun & Bradstreet and the Retail Credit Co. (today Equifax ); many essential workers in at least a dozen cities, on the other hand, received none. The agreement between PHS and the manufacturers on a "voluntary" system of allocation, in other words, "was generally ignored." On 24 September, PHS announced that it had requested, more specifically, that the vaccine manufacturers fill orders in accordance with state and local priority recommendations, in addition to the population-based system of allocation. Confusion surrounding vaccination priorities plagued even federal agencies. In October, The Evening Star reported of a "major foul-up" in the provision of vaccine to government employees. The Civil Service Commission , among some other agencies, had been inoculating any who applied, while others, such as the Commerce Department , had been giving vaccine only to those deemed "essential", such as air traffic controllers within the Civil Air Administration . The director of personnel at the Commerce Department, Carlton Hayward, expressed plainly that the process had been "handled sloppily". Hayward's assistant, John S. Myers, suggested two items to improve the allocation policy — "clearcut guidance" on this issue from PHS and specification as to whether federal agencies could use vaccine funding for those other than essential workers — noting that doing so could well save money on sick leave. Similar criticisms were echoed across the country, even as the pace of production continued to accelerate. In Boston, city councilors charged that a "lack of leadership" on the part of state and federal health authorities had created a "black market" for the vaccine, with some doctors allegedly charging "exorbitant amounts" for shots. In California, testifying before the subcommittee on intergovernmental affairs in the State Assembly , Director of the Department of Public Health Malcolm Merrill expressed his view that insufficient planning had gone into the system of allocation based on state population. Neither were the manufacturers themselves spared of criticism for their part in this vaccine "black market": After the Queens County Medical Society contacted several of the companies to protest their "maldistribution" of vaccine to such nonessential recipients as "banks, candy stores, hair net factories, etc.", the firms reportedly could offer nothing in response but "very evasive answers" and "vague explanations". With flu cases having peaked, and excess mortality at this point increasing, in the latter half of October, PHS announced the development of a more "potent" vaccine to be available by the end of November. Vaccine remained scarce in many places by the end of October, while in others supply had improved. In Oklahoma City for a water pollution control meeting, Burney provided the expectation that the epidemic would continue for 8 to 10 weeks and recommended that people should take the improved vaccine when it was available but that they should not wait if they were able to take the currently available vaccine. By early November, estimated flu cases had reached 6 million while mortality peaked during the first week of the month. Cities like Philadelphia and Washington, D.C., continued to urge those not yet inoculated to get the vaccine, at this point, in part, in an effort to ward off a potential second wave. On 8 November, with over 40 million doses released thus far, PHS announced an end to the voluntary allocation program; distributors were now free to send vaccine supplies to areas of high demand rather than attempt an equitable allocation. At the 85th annual meeting of the American Public Health Association on 14 November, PHS information chief J. Hunter Stewart addressed the vaccine situation, reporting that the time of demand exceeding supply had ended in many places and would soon end in all places across the country. With the epidemic declining in most places by early December, demand for the vaccine began to decline as well, leaving behind a considerable surplus, and manufacturers began to cut back on production. By 11 December, over 54 million doses had been released. Despite improving conditions, Burney urged continued vaccination given the possibility for another, even more severe wave later in the winter, and noted that the estimated 22 million to 25 million doses still on the way would be sufficient to control any new outbreaks until production could restart. After influenza and pneumonia mortality began to increase again in January 1958, Burney called for a second round of injections for older individuals and others in high-risk groups. Overall, this vaccination effort was considered to be a "gamble". The industry as a whole invested $20 million in production, without any subsidization by the government and with no guarantee, other than assurances from PHS, that there would be demand for the vaccine. Despite the drop in demand and the subsequent surplus as the epidemic waned, several of the manufacturers expressed little concern regarding the financial situation. Although vaccine sales had been, according to Eli Lilly & Co., "disappointing", Lederle Laboratories, for example, reported in December that the slump in sales would have little effect on their overall earnings for 1957. Parke, Davis & Co. expressed a similar sentiment, noting that the high levels of respiratory illness stimulated a significant demand for the company's other products, such as cough medicine and antibiotics. It is questionable how effective the campaign was on the whole in altering the course of the epidemic. On account of the delays in distribution, many fewer individuals actually received the vaccine than the approximately 49 million doses that had been released by the peak of the epidemic. Considering the time needed to build up antibodies following vaccination, the number of individuals "effectively immunized" was considered to be "relatively small." Reflecting on lessons learned from this episode, PHS acknowledged after the fact that "a more coherent system of allocation" would be necessary, particularly when demand far exceeds available supply. The number of deaths peaked the week ending 17 October, with 600 reported in England and Wales . The vaccine was available in the same month in the United Kingdom. Although it was initially available only in limited quantities, its rapid deployment helped contain the pandemic. Hilleman's vaccine is believed to have saved hundreds of thousands of lives. Some predicted that the U.S. death toll would have reached 1 million without the vaccine that Hilleman called for. H2N2 influenza virus continued to be transmitted until 1968, when it transformed via antigenic shift into influenza A virus subtype H3N2 , the cause of the 1968 influenza pandemic . The strain of virus that caused the Asian flu pandemic, influenza A virus subtype H2N2 , was a recombination of avian influenza (probably from geese) and human influenza viruses. As it was a novel strain of the virus, the population had minimal immunity . The reproduction number for the virus was around 1.8 and approximately two-thirds of infected individuals were estimated to have experienced clinical symptoms. It could cause pneumonia by itself without the presence of secondary bacterial infection . It caused many infections in children, spread in schools, and led to many school closures. However, the virus was rarely fatal in children and was most deadly in pregnant women, the elderly, and those with pre-existing heart and lung disease. In October 1957, Leroy Edgar Burney told The New York Times that the pandemic is mild and the case fatality rate (CFR) is below "two-thirds of 1 per cent", or less than 0.67%. After the pandemic, information from 29 general practices in the UK estimated 2.3 deaths per 1,000 medically attended cases. A survey based on randomly selected families in Kolkata, India, revealed that there were 1,055 deaths in 1,496,000 cases. On the symposium of Asian influenza in 1958, a range of CFR from 0.01% to 0.33% was provided, most frequently in between 0.02% and 0.05%. More recently, the World Health Organization estimated the CFR of Asian flu to be lower than 0.2%. In the US pandemic preparedness plan, the CDC estimated the CFR of 1957 pandemic to be 0.1%. The estimated CFR from first wave morbidity and excess mortality in Norway is in between 0.04% and 0.11%. Other scholars estimated the CFR near 0.1%. The flu may have infected as many as or more people than the 1918 Spanish flu pandemic , but the vaccine, improved health care, and the invention of antibiotics to manage opportunistic bacterial infections contributed to a lower mortality rate. Most estimates of excessive deaths due to the pandemic range from 1-4 million, some of which include years beyond 1958. In particular, the attempt by the National Institutes of Health in 2016 attributed global mortality 1.1 million (0.7 to 1.5 million) excess deaths to the pandemic, including the year 1959. This estimate of global burden has recently been adopted by the World Health Organization and US CDC . The study also estimated the excess deaths in the first year of the pandemic, in 1957, to be 0.6 million (0.4 to 0.8 million). The Dow Jones Industrial Average lost 15% of its value in the second half of 1957, and the U.S. experienced a recession . In the United Kingdom , the government paid out £10,000,000 in sickness benefit , and some factories and mines had to close. Many schools had to close in Ireland , including seventeen in Dublin .

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Pandemic influenza

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1510 influenza pandemic

In 1510, an acute respiratory disease emerged in Asia before spreading through North Africa and Europe during the first chronicled, inter-regional flu pandemic generally recognized by medical historians and epidemiologists. Influenza-like illnesses had been documented in Europe since at least Charlemagne , with 1357's outbreak the first to be called influenza , but the 1510 flu pandemic is the first to be pathologically described following communication advances brought about by the printing press . Flu became more widely referred to as coqueluche and coccolucio in France and Sicily during this pandemic, variations of which became the most popular names for flu in early modern Europe . The pandemic caused significant disruption in government, church, and society with near-universal infection and a mortality rate of around 1%. The 1510 flu is suspected of originating in East Asia, possibly China . Gregor Horst writes in Operum medicorum tombus primus (1661) that the disease came from Asia and spread along trade routes before attacking the Middle East and North Africa. German medical writer Justus Hecker suggested the 1510 influenza most likely came from Asia because of the historical nature of other influenzas to originate there in more recent pandemics. The flu spread along trade routes towards North Africa, traveling southwest through the Middle East. Frequently visited cities like Jerusalem and Mecca would have almost certainly been reached by the flu, with large volumes of people destined to travel to Egypt , North Africa, and the Ottoman Empire . [ citation needed ]The flu spread along trade routes towards North Africa, traveling southwest through the Middle East. Frequently visited cities like Jerusalem and Mecca would have almost certainly been reached by the flu, with large volumes of people destined to travel to Egypt , North Africa, and the Ottoman Empire . [ citation needed ]It is generally understood that the 1510 influenza had spread in Africa before Europe. Influenza was likely widespread in North Africa before crossing continents through the Mediterranean, arriving in Malta where British medical historian Thomas Short believed that the "island of Melite in Africa " became the 1510 flu's springboard into Europe. Europe's internationally traveled cities and flu's highly contagious nature enabled its spread through European populations. The 1510 flu disrupted royal courts, church services, and social life across Europe. Contemporary chroniclers and those who have read their accounts observed how entire populations were attacked at once, which is how the disease first received the name influenza (from the belief that such outbreaks were caused by influences like stars or cold). Turin professor Francisco Vallerioli (aka Valleriola) writes that the 1510 flu featured "Constriction of breathing, and beginning with a hoarseness of voice and... shivering. Not long after that there being a cooked humor which fills the lungs." Physicians like Valleriola described the 1510 flu as more fatal to children and those who were bled. Lawyer Francesco Muralto noted that "the disease killed 10 people out of a thousand in one day," supporting a fatality rate of around 1%. The first cases of influenza began to appear in Sicily around July after the arrival of infected merchant ships from Malta . In Sicily it was commonly called coccolucio for the hood (resembling a coqueluchon - a kind of monk's cowl) the sick often wore over their heads. Influenza quickly spread out along the Mediterranean coasts of Italy and southern France via merchant ships leaving the island. In Emilia-Romagna , Tommasino de' Bianchi recorded the recovery of Modena's first cases on 13 July 1510, writing that in the city "there appears an illness that lasts three days with a great fever, and headache and then they rise... but there remains a terrible cough that lasts maybe eight days, and then they recover." This data would indicate that the first cases of flu, which has an incubation period of one to four days, began to fall ill in the Emilia-Romagna region around late June or early July. Pope Julius II attributed the outbreaks in Rome and the Holy See to God's wrath. Flu spread over the Alps into Switzerland and the Holy Roman Empire . In Switzerland it is documented as being called das Gruppie by the Mellingen chronicler Anton Tegenfeld, the flu nickname then preferred by German-speaking Europeans. A respiratory illness seemed to have menaced the Canton of Aargua in June, with the population falling ill with sniffling, coughing, and fatigue. German physician Achilles Gasser recorded a deadly epidemic spreading over the Holy Roman Empire's upper kingdoms, branching into the cities and the "whole mankind:" Mira qua edam Epidemia mortales per urbes hanc totamque adeo superiorem Germaniam corripiebat, qua aegri IV vel V ad summum dies molestissimis destillationibus laborabant ac ration privati instar phrenicorum furebant, atque inde iterum convalescebant, paucissimis ad Gorcum demissis. André de Burgo's letters dated 24 August 1510 indicate Margaret of Austria had to intervene at a royal assembly between her father, Holy Roman Emperor Maximilian I , and Louis XII of France because the King of France was too sick with "coqueluche" to be spoken to. Influenza spread out from the Holy Roman Empire towards Northern Europe, the Baltic states , and west towards France and England . Arriving aboard infected sailors from Sicily, influenza struck the Kingdom of France through the ports of Marseille and Nice and spread through the international crowds of the shipyards. Merchants, pilgrims, and other travelers from the south and east spread the virus throughout the western Mediterranean in July. It was referred to as " cephalie catarrhal " among French physicians, but more commonly just called coqueluche . Historian François Eudes de Mézeray traced the etymology of "coqueluche" to an outbreak 1410s during which sufferers wore hoods resembling coqueluchons, a kind of monk's cowl. French surgeon Ambroise Paré described the outbreak as having been a "rheumatic affliction of the head...with constriction of the heart and lungs." By August it had appeared in Tours and after it had propagated itself throughout France over summer, sickening the entire country by September. French poet and historian Jean Bouchet, employed by King Louis XII's Royal Court, wrote that the epidemic "appeared in the entire Kingdom of France, as much in the towns as in the countryside." Coqueluche filled up the hospitals in France. King Louis XII's National Assembly of Bishops , Prelates , and university professors scheduled for September 1510 was delayed because of the intensity of the flu in Paris . Jean Fernel (aka Fernelius), physician to Henry III of France , compares the 1557 influenza to the 1510 epidemic which attacked everyone with fever, a heaviness in their head, and profound coughing. Up to 1000 Parisians per day were dying at the height of the "1510 peste." Mézeray mentions that it disrupted judicial proceedings and colleges, and that the 1510 flu was more widespread and deadly in France than in other countries. Cardinal Georges d'Amboise , a close friend and advisor to the King of France, is sometimes believed to have died of influenza since his health sharply declined after arriving in Lyons in May 1510. The cardinal, also known as Monseigneur le Ledat, made his final testimony and recited Sacraments around 22 May before he died on the 25th. His sudden decline in health and flu's arrival in Europe around early summer have created uncertainty as to whether he died of gout or influenza, but "coqueluche" is not mentioned in French royal correspondence that year until August. British medical historian Charles Creighton claimed there is one foreign account of the 1510 flu in England, but did not elaborate. Fernel and Paré suggested that the 1510 influenza "spread to almost all countries of the world" (not concerning Spain's territories in the New World). An epidemiological study of past influenza pandemics reviewing previous medical historians' data has found England was affected in 1510 and there were reports of symptoms like "gastrodynia" and noteworthy murrain among cattle. The 1510 flu is also recorded to have reached Ireland . Influenza reached the Iberian Peninsula early after Italy, due to the highly interconnected trade and pilgrimage routes between Spain, Portugal, and the Italian kingdoms. Cases began to appear in Portugal around the same time the disease entered the Holy Roman Empire. Spanish cities were reportedly "dispopulated" by the 1510 flu. The first cases of influenza began to appear in Sicily around July after the arrival of infected merchant ships from Malta . In Sicily it was commonly called coccolucio for the hood (resembling a coqueluchon - a kind of monk's cowl) the sick often wore over their heads. Influenza quickly spread out along the Mediterranean coasts of Italy and southern France via merchant ships leaving the island. In Emilia-Romagna , Tommasino de' Bianchi recorded the recovery of Modena's first cases on 13 July 1510, writing that in the city "there appears an illness that lasts three days with a great fever, and headache and then they rise... but there remains a terrible cough that lasts maybe eight days, and then they recover." This data would indicate that the first cases of flu, which has an incubation period of one to four days, began to fall ill in the Emilia-Romagna region around late June or early July. Pope Julius II attributed the outbreaks in Rome and the Holy See to God's wrath. Flu spread over the Alps into Switzerland and the Holy Roman Empire . In Switzerland it is documented as being called das Gruppie by the Mellingen chronicler Anton Tegenfeld, the flu nickname then preferred by German-speaking Europeans. A respiratory illness seemed to have menaced the Canton of Aargua in June, with the population falling ill with sniffling, coughing, and fatigue. German physician Achilles Gasser recorded a deadly epidemic spreading over the Holy Roman Empire's upper kingdoms, branching into the cities and the "whole mankind:" Mira qua edam Epidemia mortales per urbes hanc totamque adeo superiorem Germaniam corripiebat, qua aegri IV vel V ad summum dies molestissimis destillationibus laborabant ac ration privati instar phrenicorum furebant, atque inde iterum convalescebant, paucissimis ad Gorcum demissis. André de Burgo's letters dated 24 August 1510 indicate Margaret of Austria had to intervene at a royal assembly between her father, Holy Roman Emperor Maximilian I , and Louis XII of France because the King of France was too sick with "coqueluche" to be spoken to. Influenza spread out from the Holy Roman Empire towards Northern Europe, the Baltic states , and west towards France and England . Arriving aboard infected sailors from Sicily, influenza struck the Kingdom of France through the ports of Marseille and Nice and spread through the international crowds of the shipyards. Merchants, pilgrims, and other travelers from the south and east spread the virus throughout the western Mediterranean in July. It was referred to as " cephalie catarrhal " among French physicians, but more commonly just called coqueluche . Historian François Eudes de Mézeray traced the etymology of "coqueluche" to an outbreak 1410s during which sufferers wore hoods resembling coqueluchons, a kind of monk's cowl. French surgeon Ambroise Paré described the outbreak as having been a "rheumatic affliction of the head...with constriction of the heart and lungs." By August it had appeared in Tours and after it had propagated itself throughout France over summer, sickening the entire country by September. French poet and historian Jean Bouchet, employed by King Louis XII's Royal Court, wrote that the epidemic "appeared in the entire Kingdom of France, as much in the towns as in the countryside." Coqueluche filled up the hospitals in France. King Louis XII's National Assembly of Bishops , Prelates , and university professors scheduled for September 1510 was delayed because of the intensity of the flu in Paris . Jean Fernel (aka Fernelius), physician to Henry III of France , compares the 1557 influenza to the 1510 epidemic which attacked everyone with fever, a heaviness in their head, and profound coughing. Up to 1000 Parisians per day were dying at the height of the "1510 peste." Mézeray mentions that it disrupted judicial proceedings and colleges, and that the 1510 flu was more widespread and deadly in France than in other countries. Cardinal Georges d'Amboise , a close friend and advisor to the King of France, is sometimes believed to have died of influenza since his health sharply declined after arriving in Lyons in May 1510. The cardinal, also known as Monseigneur le Ledat, made his final testimony and recited Sacraments around 22 May before he died on the 25th. His sudden decline in health and flu's arrival in Europe around early summer have created uncertainty as to whether he died of gout or influenza, but "coqueluche" is not mentioned in French royal correspondence that year until August. British medical historian Charles Creighton claimed there is one foreign account of the 1510 flu in England, but did not elaborate. Fernel and Paré suggested that the 1510 influenza "spread to almost all countries of the world" (not concerning Spain's territories in the New World). An epidemiological study of past influenza pandemics reviewing previous medical historians' data has found England was affected in 1510 and there were reports of symptoms like "gastrodynia" and noteworthy murrain among cattle. The 1510 flu is also recorded to have reached Ireland . Influenza reached the Iberian Peninsula early after Italy, due to the highly interconnected trade and pilgrimage routes between Spain, Portugal, and the Italian kingdoms. Cases began to appear in Portugal around the same time the disease entered the Holy Roman Empire. Spanish cities were reportedly "dispopulated" by the 1510 flu. There are no records of influenza affecting the New World in 1510, even though Spain was sending fleets of ships across the Atlantic. The first recorded flu outbreak in the New World had afflicted the Isle of Santo Domingo (Now Haiti and the Dominican Republic ) in 1493 . Amerindian populations sharp decline due to Spanish-imported diseases in these 1490s and early 1500s is however documented, most notably due to smallpox . [ citation needed ]Blistering on the back of the head and shoulders was one form of treatment prescribed in Europe for the flu. Paré regarded the common treatments of bloodletting and purgation to be especially dangerous to 1510's flu patients. Supraorbital pain and vision problems were symptoms of coqueluche , so sufferers may have felt tempted to wear hoods due to light sensitivity. Short describes some medicinal treatments for the 1510 flu including "Bole Armoniac, oily lintus, pectoral troches, and decoctions." Justus Hecker and John Parkin presumed the 1510 influenza originated from East Asia because of the historical nature of other influenza pandemics to originate there, while in 1661 Gregor Horst wrote that the 1510 flu spread along trade routes from East Asia to Africa before reaching Europe. Influenza viruses sometimes leap from Asia's migratory water fowl after massive migrations congregate near water sources for humans and domesticated animals, in which cross-species infections trigger antigenic shift and create new strains of flu human beings have little immunity to. European chroniclers noticed that the 1510 influenza did appear in North Africa before Europe, which has led some medical historians to suggest it may have developed there (parts of North Africa also lie along migratory bird ways, specifically the east Africa-West Asia and Black Sea-Mediterranean routes, that make it vulnerable to spontaneous reassortment of pandemic flu viruses). There remains no chronicled or biological evidence to suggest the 1510 flu originated from, as opposed to just spread in, Africa before reaching Europe. [ citation needed ]The 1510 "coqueluche" has been recognized as influenza by modern epidemiologists and medical historians. Suggestions that the 1510 coqueluche was whooping cough have been doubted because adult sufferers often experienced "precipitous" symptoms described by contemporaries like Tommasino de Bianchi or Valleriola as high fever for 3 days, headache, prostration, loss of sleep and appetite, delirium, a cough most severe on the 5th to 10th days, lung congestion, and slow recovery beginning on the second week. Adults with pertussis will usually cough for weeks before becoming gradually more ill then recovering over a period of months. The coqueluche of 1510 is considered to be influenza by experts because of its sudden symptoms, explosive spread, and timelines of sickness to recovery. The first outbreak of whooping cough to be agreed on by most medical historians is Guillaume de Baillou's description of an outbreak in Paris in 1578 .

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Pandemic influenza

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1557 influenza pandemic

In 1557, a pandemic strain of influenza emerged in Asia , then spread to Africa , Europe , and eventually the Americas . This flu was highly infectious and presented with intense, occasionally lethal symptoms. Medical historians like Thomas Short , Lazare Rivière and Charles Creighton gathered descriptions of catarrhal fevers recognized as influenza by modern physicians attacking populations with the greatest intensity between 1557 and 1559. The 1557 flu saw governments, for possibly the first time, inviting physicians to instill bureaucratic organization into epidemic responses. It is also the first pandemic where influenza is pathologically linked to miscarriages , given its first English names, and is reliably recorded as having spread globally. Influenza caused higher burial rates, near-universal infection, and economic turmoil as it returned in repeated waves.According to a European chronicler surnamed Fonseca who wrote Disputat. de Garotillo, the 1557 influenza pandemic first broke out in Asia . The flu spread west along established trade and pilgrimage routes before reaching the Ottoman Empire and the Middle East . An epidemic of a flu-like illness is recorded for September 1557 in Portuguese Goa . In the summer of 1557 parts of Europe had just suffered outbreaks of plague , typhus , measles , and smallpox when influenza arrived from the Ottoman Empire and North Africa . The flu spread west through Europe aboard merchant ships in the Mediterranean Sea , again taking advantage of trade and pilgrimage routes. Death rates were highest in children, those with preexisting conditions, the elderly, and those who were bled. Outbreaks were particularly severe in communities suffering from food scarcity. The epidemics of fevers and respiratory illness eventually became referred to as the new sickness in England, new acquaintance in Scotland, and coqueluche or simply catarrh by medical historians in the rest of Europe. Because it afflicted entire populations at once in mass outbreaks, some contemporary scholars thought the flu was caused by stars, contaminated vapors brought about by damp weather, or the dryness of the air. Ultimately the 1557 flu lasted in varying waves of intensity for around four years in epidemics that increased European death rates, disrupted the highest levels of society, and frequently spread to other continents. The flu pandemic first reached Europe in 1557 from the Ottoman Empire along trade and shipping routes connected to Constantinople , brought to Asia Minor by infected travelers from the Middle East. At the time, the Ottoman Empire's territory included most of the Balkans and Bulgaria. This gave influenza unrestricted access to Athens , Sofia , and Sarajevo as it spread throughout the empire. Influenza set sail from the capital, Constantinople, into the recently conquered North African territories of Tripoli (1551) and the Habesh (1557), from where it likely ricocheted to Malta from North Africa via merchant ships, as during the pandemic of 1510 . On land, influenza spread north from the Ottoman Empire over Wallachia to the Kingdom of Poland and Grand Duchy of Lithuania before moving west into continental Europe. [ citation needed ] Influenza arrived in the Kingdom of Sicily in June at Palermo , whence it spread across the island. Church services, Sicilian social life, and the economy were disrupted as the flu sickened a large portion of the population. The Sicilian Senate asked a well-known Palermitan physician named Giovanni Filippo Ingrassia to help combat the epidemic in an advisory capacity, which he accepted. Ingrassia approached epidemic responses as a collaboration between healthcare and government officials, and was the first known "health care professional" to propose that a system for monitoring epidemics of contagious catarrhal fevers would aid in early detection and epidemic control. Flu spread quickly from Sicily into the Kingdom of Naples on the lower part of the Italian Peninsula , moving upward along the coastline. In Urbino , Venetian court poet Bernardo Tasso , his son Torquato , and the occupants of a monastery fell sick "from hand to hand" with influenza for four to five days. Though the epidemic left the entire city of Urbino ill, most individuals recovered without complications. By the time Bernardo had traveled to northern Italy on August 3 the disease had already spread into the rest of Europe. In Lombardy there was an outbreak of "suffocating catarrh" that could quickly become fatal. The symptoms were so severe that some members of the population suspected a mass poisoning had occurred. Padua began to see cases in August, with sickness lasting into September. German medical historian Justus Hecker writes that the young population of Padua had been reeling from a dual outbreak of measles and smallpox since the spring when a new illness, featuring extreme cough and headache, began to afflict the citizens in late summer. The illness was referred to as coqueluche. Switzerland was also reached by the disease in August. "Catarrh" swept through the Swiss plateaus from August to September and almost disrupted the graduate studies of Swiss physician Felix Plater , who was sickened by severe fits of coughing while a candidate for his doctorate. French physician and medical historian Lazare Rivière documented an anonymous physician's descriptions of a flu outbreak occurring in the Languedoc region of France in July 1557. The disease, often called coqueluche by the French, caused a severe outbreak in Nîmes that featured a fast onset of symptoms like headaches, fevers, loss of appetite, fatigue, and intense coughing. Most of those who died from the disease did so on the fourth day, but some succumbed up to 11 days after first symptoms. Across Languedoc influenza had a high mortality rate, with up to 200 people per day dying in Toulouse at the height of the region's epidemic. Italian physician Francisco Vallerioli, known as François Valleriola, was a witness to the epidemic in France and described the 1557 flu's symptoms as featuring a fever, severe headache, intense coughing, shortness of breath, chills, hoarseness, and expulsion of phlegm after 7 to 14 days. French lawyer Étienne Pasquier wrote that the disease began with a severe pain in the head and a 12- to 15-hour fever while sufferers' noses "ran like a fountain." Paris saw its judiciary disrupted when the Paris Law Court suspended its meetings to slow the spread of flu. Medical historian Charles-Jacques Saillant described this influenza as especially fatal to those who were treated with bleeding and very dangerous to children. The 1557 influenza severely impacted the British Isles. British medical historian Charles Creighton cited a contemporary writer, Wriothesley, who noted in 1557 "this summer reigned in England divers strange and new sicknesses, taking men and women in their heads; as strange agues and fevers, whereof many died." 18th Century physician Thomas Short wrote that those who succumbed to the flu "were let blood of or had unsound viscera." Flu blighted the army of Mary I of England by leaving her government unable to train sufficient reinforcements for Henry Manners, 2nd Earl of Rutland to protect Calais from an impending French assault, and by January 1558 the Duke of Guise had claimed the under-protected city in the name of France. Influenza significantly contributed to England's unusually high death rates for 1557–58: Data compiled on over 100 parishes in England found that the mortality rates increased by up to 60% in some areas during the flu epidemic, even though diseases like true plague were not heavily present in England at the time. Dr. Short found that the number of burials for market towns was much higher than christenings from 1557 to 1562. For example, the annual number of burials in Tonbridge increased from 33 on average in 1556 to 61 in 1557, 105 in 1558, and 94 in 1559. Before the flu epidemic, England had suffered from a poor harvest and widespread famine that medical historian Thomas Short believed made the epidemic more deadly. Influenza returned in 1558. Contemporary historian John Stow wrote that during "winter the quarterne agues continued in like manner" to 1557's epidemic. On 6 September 1558 the Governor of the Isle of Wight , Lord St. John , wrote in a despatch to Mary I of England about a highly-contagious illness afflicting more than half the people of Southampton , the Isle of Wight, and Portsmouth (places where Lord St. John had stationed troops). A second despatch from 11 P.M. of 6 October indicated "from the mayor of Dover that there is no plague there, but the people that daily die are those that come out of the ships, and such poor people as come out of Calais, of the new sickness." One of the commissioners for the surrender of Calais found Sir William Pickering, former knight-marshal to King Henry VIII , "very sore of this new burning ague. He has had four sore fits, and is brought very low, and in danger of his life if they continue as they have done." Influenza began to move north through England, felling numerous farmers and leaving large quantities of grain unharvested before it reached London around mid-late October. Queen Mary and Archbishop of Canterbury Reginald Pole , who had both been in poor health before flu broke out in London, likely died of influenza within 12 hours of each other on 17 November 1558. Two of Mary's physicians died as well. Ultimately around 8000 other Londoners likely died of influenza during the epidemic, including many elders and parish priests. New waves of "agues" and fevers were recorded in England into 1559. These repeated outbreaks proved unusually deadly for populations already suffering from extensive rains and poor harvests. From 1557 to 1559 the nation's population contracted by 2%. The sheer numbers of people dying from epidemics and famine in England caused economic inflation to flatten out. In the late 1550s the English language had not yet developed a proper name for the flu, despite previous epidemics. Thus 1557's epidemic was either described as a "plague" (like many epidemics with notable mortality), "ague" (most generally) or "new disease" in England. "The sweat" was one name used to describe the usually deadly, flu-like fevers and "agues" plaguing the English countryside from 1557 to 1558, despite no reliable records of sweating sickness after 1551. Doctor John Jones, a prominent 16th Century London physician, refers in his book Dyall of Agues to a "great sweat" during the reign of Mary I of England. After the 1557 pandemic English nicknames for the flu began to appear in letters, like "the new disease" in England and "the newe acquaintance" in Scotland. When the entire royal court of Mary, Queen of Scots was struck down with influenza in Edinburgh in November 1562, Lord Randolph described the outbreak as "a new disease, that is common in this town, called here 'the newe acquaintance,' which passed also through her whole court, neigh sparing lord, lady, nor damoysell, not so much as either French or English. It is a pain in their heads that have it, and a soreness in their stomachs, with a great cough, that remaineth with some longer with other short time, as it findeth apt bodies for the nature of the disease...There was not an appearance of danger, nor manie that died of the disease, except some old folks." Mary Stuart herself spent six days sick in her bedchambers. Habsburg Netherlands was also heavily impacted by the flu in October. Dutch historian Petrus Forestus described an outbreak in Alkmaar where 2000 fell sick with flu and 200 perished in a span of three weeks. Forestus himself became sick with the flu and related that it "...began with a slight fever like a common catarrh, and showed its great malignancy only by degrees. Sudden fits of suffocation then came on, and the pain of the chest was so distressing that patients imagined they must die in the paroxysm . The complaint was increased still by a tight, convulsive cough. Death did not take place till the 9th or 14th day." He further observed that the flu was very dangerous to pregnant women, killing at least eight such citizens in Alkmaar who contracted it. Influenza's symptoms came on suddenly and attacked thousands of the city's residents at the same time. Hunger likely contributed to a higher death toll, as the authorities had been struggling to provide food to the needy amid a severe bread shortage during the summer. Attempting to explain the epidemic of fevers and respiratory illness affecting the Low Countries , Flemish physician Rembert Dodoens suggested that the mass outbreaks of illness were caused by a dry, hot summer following a very cold winter. Spain was widely and severely impacted by influenza, which chroniclers recognized as a highly contagious catarrhal fever. Influenza likely arrived in Spain around July, with the first cases being reported near Madrid in August. British medical historian Thomas Short wrote that "At Mantua Carpentaria, three miles outside of Madrid, the first cases were reported...There it began with a roughness of the jaws, small cough, then a strong fever with a pain in the head, back, and legs. Some felt as though they were corded over the breast, with a weight at the stomach, all which continued to the third day at the furthest. Then the fever went off, with a sweat of bleeding at the nose. In some few, it turned to a pleurisy of fatal peripneumony." Bloodletting greatly increased the risk of mortality, and it was observed in Mantua Carpentaria that "2000 were let blood of and all died." The flu then entered Spain's capital city, where it rapidly spread to all parts of the Spanish mainland. [ citation needed ] Cases expanded exponentially as merchants, pilgrims, and other travelers leaving Madrid transported the virus to cities and towns across the country. According to King Phillip II's doctor Luis de Mercado, "All the population was attacked the same day, and the same time of day. It was catarrh, marked by fever of the double tertian type, with such pernicious symptoms that many died." The season's poor harvests and hunger in the Spanish population, as well as negligent medical care, likely contributed to the severity of the influenza pandemic in Spain . Flu symptoms could be so intense that the region's physicians often distinguished it from other contagious, seasonal pneumonias that spread from East Europe. Sixteenth century Spaniards frequently referred to any mass outbreak of deadly disease generically as a pestilencia , and "plagues" are recognized as occurring in Valencia and Granada during the years 1557–59, despite pathological records of true plague (like descriptions of buboes) occurring in the area at the time being scant. Influenza hit the Kingdom of Portugal at the same time as it spread throughout Spain, with an impact that spread across the Atlantic Ocean. The kingdom had just suffered food shortages due to 1556-57's poor harvest, which would have exacerbated the effects of the flu on hungry patients. A violent storm had just hit Portugal and severely damaged the Palace of Enxobregas, and in following with attributing outbreaks of influenza to the weather Portuguese historians like Ignácio Barbosa-Machado attributed the epidemic in the kingdom to the storm with little opposition. Barbosa-Machado referred to 1557 as the "anno de catarro." The flu pandemic first reached Europe in 1557 from the Ottoman Empire along trade and shipping routes connected to Constantinople , brought to Asia Minor by infected travelers from the Middle East. At the time, the Ottoman Empire's territory included most of the Balkans and Bulgaria. This gave influenza unrestricted access to Athens , Sofia , and Sarajevo as it spread throughout the empire. Influenza set sail from the capital, Constantinople, into the recently conquered North African territories of Tripoli (1551) and the Habesh (1557), from where it likely ricocheted to Malta from North Africa via merchant ships, as during the pandemic of 1510 . On land, influenza spread north from the Ottoman Empire over Wallachia to the Kingdom of Poland and Grand Duchy of Lithuania before moving west into continental Europe. [ citation needed ]Influenza arrived in the Kingdom of Sicily in June at Palermo , whence it spread across the island. Church services, Sicilian social life, and the economy were disrupted as the flu sickened a large portion of the population. The Sicilian Senate asked a well-known Palermitan physician named Giovanni Filippo Ingrassia to help combat the epidemic in an advisory capacity, which he accepted. Ingrassia approached epidemic responses as a collaboration between healthcare and government officials, and was the first known "health care professional" to propose that a system for monitoring epidemics of contagious catarrhal fevers would aid in early detection and epidemic control. Flu spread quickly from Sicily into the Kingdom of Naples on the lower part of the Italian Peninsula , moving upward along the coastline. In Urbino , Venetian court poet Bernardo Tasso , his son Torquato , and the occupants of a monastery fell sick "from hand to hand" with influenza for four to five days. Though the epidemic left the entire city of Urbino ill, most individuals recovered without complications. By the time Bernardo had traveled to northern Italy on August 3 the disease had already spread into the rest of Europe. In Lombardy there was an outbreak of "suffocating catarrh" that could quickly become fatal. The symptoms were so severe that some members of the population suspected a mass poisoning had occurred. Padua began to see cases in August, with sickness lasting into September. German medical historian Justus Hecker writes that the young population of Padua had been reeling from a dual outbreak of measles and smallpox since the spring when a new illness, featuring extreme cough and headache, began to afflict the citizens in late summer. The illness was referred to as coqueluche. Switzerland was also reached by the disease in August. "Catarrh" swept through the Swiss plateaus from August to September and almost disrupted the graduate studies of Swiss physician Felix Plater , who was sickened by severe fits of coughing while a candidate for his doctorate.French physician and medical historian Lazare Rivière documented an anonymous physician's descriptions of a flu outbreak occurring in the Languedoc region of France in July 1557. The disease, often called coqueluche by the French, caused a severe outbreak in Nîmes that featured a fast onset of symptoms like headaches, fevers, loss of appetite, fatigue, and intense coughing. Most of those who died from the disease did so on the fourth day, but some succumbed up to 11 days after first symptoms. Across Languedoc influenza had a high mortality rate, with up to 200 people per day dying in Toulouse at the height of the region's epidemic. Italian physician Francisco Vallerioli, known as François Valleriola, was a witness to the epidemic in France and described the 1557 flu's symptoms as featuring a fever, severe headache, intense coughing, shortness of breath, chills, hoarseness, and expulsion of phlegm after 7 to 14 days. French lawyer Étienne Pasquier wrote that the disease began with a severe pain in the head and a 12- to 15-hour fever while sufferers' noses "ran like a fountain." Paris saw its judiciary disrupted when the Paris Law Court suspended its meetings to slow the spread of flu. Medical historian Charles-Jacques Saillant described this influenza as especially fatal to those who were treated with bleeding and very dangerous to children. The 1557 influenza severely impacted the British Isles. British medical historian Charles Creighton cited a contemporary writer, Wriothesley, who noted in 1557 "this summer reigned in England divers strange and new sicknesses, taking men and women in their heads; as strange agues and fevers, whereof many died." 18th Century physician Thomas Short wrote that those who succumbed to the flu "were let blood of or had unsound viscera." Flu blighted the army of Mary I of England by leaving her government unable to train sufficient reinforcements for Henry Manners, 2nd Earl of Rutland to protect Calais from an impending French assault, and by January 1558 the Duke of Guise had claimed the under-protected city in the name of France. Influenza significantly contributed to England's unusually high death rates for 1557–58: Data compiled on over 100 parishes in England found that the mortality rates increased by up to 60% in some areas during the flu epidemic, even though diseases like true plague were not heavily present in England at the time. Dr. Short found that the number of burials for market towns was much higher than christenings from 1557 to 1562. For example, the annual number of burials in Tonbridge increased from 33 on average in 1556 to 61 in 1557, 105 in 1558, and 94 in 1559. Before the flu epidemic, England had suffered from a poor harvest and widespread famine that medical historian Thomas Short believed made the epidemic more deadly. Influenza returned in 1558. Contemporary historian John Stow wrote that during "winter the quarterne agues continued in like manner" to 1557's epidemic. On 6 September 1558 the Governor of the Isle of Wight , Lord St. John , wrote in a despatch to Mary I of England about a highly-contagious illness afflicting more than half the people of Southampton , the Isle of Wight, and Portsmouth (places where Lord St. John had stationed troops). A second despatch from 11 P.M. of 6 October indicated "from the mayor of Dover that there is no plague there, but the people that daily die are those that come out of the ships, and such poor people as come out of Calais, of the new sickness." One of the commissioners for the surrender of Calais found Sir William Pickering, former knight-marshal to King Henry VIII , "very sore of this new burning ague. He has had four sore fits, and is brought very low, and in danger of his life if they continue as they have done." Influenza began to move north through England, felling numerous farmers and leaving large quantities of grain unharvested before it reached London around mid-late October. Queen Mary and Archbishop of Canterbury Reginald Pole , who had both been in poor health before flu broke out in London, likely died of influenza within 12 hours of each other on 17 November 1558. Two of Mary's physicians died as well. Ultimately around 8000 other Londoners likely died of influenza during the epidemic, including many elders and parish priests. New waves of "agues" and fevers were recorded in England into 1559. These repeated outbreaks proved unusually deadly for populations already suffering from extensive rains and poor harvests. From 1557 to 1559 the nation's population contracted by 2%. The sheer numbers of people dying from epidemics and famine in England caused economic inflation to flatten out. In the late 1550s the English language had not yet developed a proper name for the flu, despite previous epidemics. Thus 1557's epidemic was either described as a "plague" (like many epidemics with notable mortality), "ague" (most generally) or "new disease" in England. "The sweat" was one name used to describe the usually deadly, flu-like fevers and "agues" plaguing the English countryside from 1557 to 1558, despite no reliable records of sweating sickness after 1551. Doctor John Jones, a prominent 16th Century London physician, refers in his book Dyall of Agues to a "great sweat" during the reign of Mary I of England. After the 1557 pandemic English nicknames for the flu began to appear in letters, like "the new disease" in England and "the newe acquaintance" in Scotland. When the entire royal court of Mary, Queen of Scots was struck down with influenza in Edinburgh in November 1562, Lord Randolph described the outbreak as "a new disease, that is common in this town, called here 'the newe acquaintance,' which passed also through her whole court, neigh sparing lord, lady, nor damoysell, not so much as either French or English. It is a pain in their heads that have it, and a soreness in their stomachs, with a great cough, that remaineth with some longer with other short time, as it findeth apt bodies for the nature of the disease...There was not an appearance of danger, nor manie that died of the disease, except some old folks." Mary Stuart herself spent six days sick in her bedchambers. Habsburg Netherlands was also heavily impacted by the flu in October. Dutch historian Petrus Forestus described an outbreak in Alkmaar where 2000 fell sick with flu and 200 perished in a span of three weeks. Forestus himself became sick with the flu and related that it "...began with a slight fever like a common catarrh, and showed its great malignancy only by degrees. Sudden fits of suffocation then came on, and the pain of the chest was so distressing that patients imagined they must die in the paroxysm . The complaint was increased still by a tight, convulsive cough. Death did not take place till the 9th or 14th day." He further observed that the flu was very dangerous to pregnant women, killing at least eight such citizens in Alkmaar who contracted it. Influenza's symptoms came on suddenly and attacked thousands of the city's residents at the same time. Hunger likely contributed to a higher death toll, as the authorities had been struggling to provide food to the needy amid a severe bread shortage during the summer. Attempting to explain the epidemic of fevers and respiratory illness affecting the Low Countries , Flemish physician Rembert Dodoens suggested that the mass outbreaks of illness were caused by a dry, hot summer following a very cold winter. Spain was widely and severely impacted by influenza, which chroniclers recognized as a highly contagious catarrhal fever. Influenza likely arrived in Spain around July, with the first cases being reported near Madrid in August. British medical historian Thomas Short wrote that "At Mantua Carpentaria, three miles outside of Madrid, the first cases were reported...There it began with a roughness of the jaws, small cough, then a strong fever with a pain in the head, back, and legs. Some felt as though they were corded over the breast, with a weight at the stomach, all which continued to the third day at the furthest. Then the fever went off, with a sweat of bleeding at the nose. In some few, it turned to a pleurisy of fatal peripneumony." Bloodletting greatly increased the risk of mortality, and it was observed in Mantua Carpentaria that "2000 were let blood of and all died." The flu then entered Spain's capital city, where it rapidly spread to all parts of the Spanish mainland. [ citation needed ] Cases expanded exponentially as merchants, pilgrims, and other travelers leaving Madrid transported the virus to cities and towns across the country. According to King Phillip II's doctor Luis de Mercado, "All the population was attacked the same day, and the same time of day. It was catarrh, marked by fever of the double tertian type, with such pernicious symptoms that many died." The season's poor harvests and hunger in the Spanish population, as well as negligent medical care, likely contributed to the severity of the influenza pandemic in Spain . Flu symptoms could be so intense that the region's physicians often distinguished it from other contagious, seasonal pneumonias that spread from East Europe. Sixteenth century Spaniards frequently referred to any mass outbreak of deadly disease generically as a pestilencia , and "plagues" are recognized as occurring in Valencia and Granada during the years 1557–59, despite pathological records of true plague (like descriptions of buboes) occurring in the area at the time being scant. Influenza hit the Kingdom of Portugal at the same time as it spread throughout Spain, with an impact that spread across the Atlantic Ocean. The kingdom had just suffered food shortages due to 1556-57's poor harvest, which would have exacerbated the effects of the flu on hungry patients. A violent storm had just hit Portugal and severely damaged the Palace of Enxobregas, and in following with attributing outbreaks of influenza to the weather Portuguese historians like Ignácio Barbosa-Machado attributed the epidemic in the kingdom to the storm with little opposition. Barbosa-Machado referred to 1557 as the "anno de catarro." There are records of the New World eventually being reached by the flu in 1557, brought to the Spanish and Portuguese Empires by sailors from Europe. Influenza arrived in Central America in 1557, likely aboard Spanish ships sailing to New Spain . During that year there were epidemics of flu recorded in the south Atlantic states, Gulf area, and Southwest. The Native American Cherokee appear to have been affected during this wave, and it may have spread along newly established trade routes between Spanish colonies in the New World . The flu also reached South America. Anthropologist Henry F. Dobyns described a 1557 epidemic of influenza in Ecuador in which European and Native populations were both left sick with severe coughing. In Colonial Brazil , Portuguese missionaries did not take breaks from religious activities when they became sick. Missionaries like the Society of Jesus in Brazil founder Manuel da Nóbrega continued to preach, host mass, and baptize converts in the New World even when symptomatic with contagious illnesses like influenza. As a result, flu would have quickly spread through Portuguese colonies due to mandatory church attendance. In 1559 the flu struck colonial Brazil with a wave of illness recorded along the coastal state of Bahia : That February, the region of Espírito Santo was struck by an outbreak of lung infections, dysentery, and "fevers that they say immediately attacked the hearts, and which quickly struck them down." Populations of natives attempted to flee the infection afflicting their communities, spreading influenza northward. European missionaries suspected such severe epidemics among the native populations to be a form of divine punishment, and referred to the outbreaks of pleurisy and dysentery among the natives in Bahia to be "the sword of God's wrath." Missionaries like Francisco Pires took some pity on the sick children of natives, whom they often regarded as innocent, and frequently baptized them during epidemics in the belief they'd "saved" their souls. Baptism rates in native communities were deeply connected with outbreaks of disease, and missionary policies of conducting religious activities while sick likely helped spread the flu.Influenza attacked Africa through the Ottoman Empire , which by 1557 was expanding its territories in the northern and eastern parts of the continent. Egypt , which had been conquered by the Ottoman Empire around 40 years prior, became an access point for influenza to travel south through the Red Sea along shipping routes. The pandemic's most memorable effects on the Ottoman army in Africa are recorded as part of the 1559 wave. [ citation needed ] The Kingdom of Portugal had supported the Abyssinian (Ethiopian) Empire in their war against the Ottoman expansion of the Habesh Eyalet and sent aid to their emperor, including a team with Andrés de Oviedo in 1557 who recorded the events. In 1559 the Ottoman Empire struggled with a severe wave of influenza: After the deaths of Emperor Gelawdewos and most of the Portuguese attaché in battle, the flu killed thousands of the Ottoman army's troops occupying the port city of Massawa . Massawa was claimed by the Ottomans from Medri Bahri during their conquest of Habesh in 1557, but the pandemic's 1559 wave challenged their army's hold onto territory around the city after flu cut down a large number of the Ottoman forces. Because of the epidemic Ottoman soldiers were soon recalled back to the ports, even though the emperor had been slain, and shortly afterwards Gelawdewos's brother Menas ascended to the Abyssinian throne and converted from Islam to Christianity . The Kingdom of Portugal had supported the Abyssinian (Ethiopian) Empire in their war against the Ottoman expansion of the Habesh Eyalet and sent aid to their emperor, including a team with Andrés de Oviedo in 1557 who recorded the events. In 1559 the Ottoman Empire struggled with a severe wave of influenza: After the deaths of Emperor Gelawdewos and most of the Portuguese attaché in battle, the flu killed thousands of the Ottoman army's troops occupying the port city of Massawa . Massawa was claimed by the Ottomans from Medri Bahri during their conquest of Habesh in 1557, but the pandemic's 1559 wave challenged their army's hold onto territory around the city after flu cut down a large number of the Ottoman forces. Because of the epidemic Ottoman soldiers were soon recalled back to the ports, even though the emperor had been slain, and shortly afterwards Gelawdewos's brother Menas ascended to the Abyssinian throne and converted from Islam to Christianity . Most physicians of the time subscribed to the theory of humorism , and believed the cosmos or climate directly affected the health of entire communities. Physicians treating the flu often used treatments called coctions to remove excess humors they believed to be causing illness. Dr. Thomas Short described treatments for the 1557 influenza as having included gargling "rose water, quinces, mulberries, and sealed earth." "Gentle bleeding" was used on the first day of the infection only, as frequently used medical techniques like bloodletting and purgation were often fatal for influenza. In Urbino, "diet and good governance" were recognized as common ways sufferers managed their illness. The 1557 pandemic's nature as a worldwide, highly-contagious respiratory disease with fast onset of flu-like symptoms has led many physicians, from medical historians like Charles Creighton to modern epidemiologists, to consider the causative disease as influenza. "Well documented descriptions from medical observers" who witnessed the effects of the pandemic as it spread through populations have been reviewed by numerous medical historians in the centuries since. Contemporary physicians to the 1557 flu, like Ingrassia, Valleriola, Dodoens, and Mercado, described symptoms like severe coughing , fever , myalgia , and pneumonia that all occurred within a short period of time and led to death in days if a case was to be fatal. Infections became so widespread in countries that influences like the weather, stars, and mass poisoning were blamed by observers for the outbreaks, a reoccurring pattern in influenza epidemics that has contributed to the disease's name. Prior to greater research being conducted into influenza in the 19th century, some medical historians considered the descriptions of epidemic "angina" from 1557 to be scarlet fever , whooping cough , and diphtheria . But the most striking features of scarlet fever and diphtheria, like rashes or pseudomembranes, remain unmentioned by any of the 1557 pandemic's observers and the first recognized whooping cough epidemic is a localized outbreak in Paris from 1578. These illnesses can resemble the flu in their early stages but pandemic influenza is distinguished by its fast-moving, unrestricted epidemics of severe respiratory disease affecting all ages with widespread infections and mortalities. [ citation needed ]

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Pandemic influenza

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1889–1890 pandemic

The 1889–1890 pandemic , often referred to as the " Asiatic flu " or " Russian flu ", was a worldwide respiratory viral pandemic. It was the last great pandemic of the 19th century, and is among the deadliest pandemics in history. The pandemic killed about 1 million people out of a world population of about 1.5 billion (0.067% of population). The most reported effects of the pandemic took place from October 1889 to December 1890, with recurrences in March to June 1891, November 1891 to June 1892, the northern winter of 1893–1894, and early 1895. According to researchers' estimates, excess mortality from Russian influenza in the Russian Empire for the period 1889–1890 could be from 60,000 to 90,000 people, with lethality from the virus, a little more than 0.2%. Although contemporaries described the pandemic as influenza and 20th-century scholars identified several influenza strains as the possible pathogen, several authors from the early 2020s suggest that it may have been caused by human coronavirus OC43 . Modern transport infrastructure assisted the spread of the 1889 pandemic. The 19 largest European countries, including the Russian Empire , had about 200,000 km of railroads, and transatlantic travel by sea took less than six days (not significantly different from current travel time by air, given the timescale of the global spread of a pandemic). It was the first pandemic to spread not just through a region such as Eurasia , but worldwide. It is conventionally believed that the disease was first reported in May 1889 in the Central Asian city of Bukhara (modern Uzbekistan), then the capital of the Emirate of Bukhara , a protectorate of the Russian Empire. This goes back to publications of a local physician and follower of the miasma theory Oskar Heyfelder, who ignored the lack of catarrhal symptoms in the outbreak. Both a local independent commission of four doctors in August 1889 and historians in 2023 identified the infectious agent in Bukhara from May to August 1889 as not influenza, but malaria, which is endemic in the region, and the latter suggested anomalously cold and snowy winter and anomalously high ground water levels as possible reasons for the severeness of the outbeak. Most likely the first outbreak of Russian flu occurred in Western Siberia – Tomsk province. It was preceded by an epizootic of pneumonia in cattle. It is also conventionally believed that the newly built Trans-Caspian railway enabled the disease to spread farther into Samarkand by August, and Tomsk , 3,200 km away, by October. However, the Russian military had not detected any flu in Samarkand in August, and despite a significant military presence along the railway the first flu cases were not diagnosed in the Turkestan Military District at all until late November. Despite the fact that the Trans-Siberian Railway had not yet been constructed (which is often cited as the reason for slow transmission of the virus to European Russia), the anomalous rise in flu cases was detected in the military in the second half of October from multiple European cities all the way to 108th meridian east . By November the pandemic had reached Saint Petersburg (infecting 180,000 of the city's under one million inhabitants) and Moscow . By mid-November Kyiv was infected, and the next month the Lake Baikal region was as well, followed by the rest of Siberia and Sakhalin by the end of the year. From St. Petersburg, the infection spread via the Baltic shipping trade to Vaxholm in early November 1889, and then to Stockholm and the rest of Sweden, infecting 60% of the population within eight weeks. Norway, and then Denmark, followed soon after. The German Empire first received it in Posen in December, and on 12 November 600 workers were reported sick in Berlin and Spandau , with the cases in the city reaching 150,000 within a few days, and ultimately half of its 1.5 million inhabitants. Vienna was infected around the same time. Rome was reached by 17 December. The flu also arrived in Paris in December, and towards the end of the month had spread to Grenoble , Toulon , Toulouse and Lyon on the mainland, and Ajaccio on Corsica . At this point Spain was also infected, killing up to 300 a day in Madrid . It reached London at the same time, from where it spread quickly within Great Britain and Ireland to Birmingham , Glasgow , Edinburgh , and Dublin . The first case on American soil was reported on 18 December 1889. It then quickly spread throughout the East Coast and all the way to Chicago and Kansas in days. The first American death, Thomas Smith of Canton, Massachusetts , was reported on 25 December. San Francisco and other cities were also reached before the month was over, with the total US death toll at about 13,000. From there it spread to Mexico and to South America, reaching Buenos Aires by 2 February. India received it in February 1890, and Singapore and the Dutch East Indies (now Indonesia) did by March. These were followed by Japan, Australia, and New Zealand by April, and then China in May; the infection continued to spread, reaching its original starting point in Central Asia. Cases in Africa began to appear in port cities in late December 1889 and in January 1890, although there may have been an early outbreak in Durban , South Africa, in November 1889. In four months it had spread throughout the Northern Hemisphere. Deaths peaked in Saint Petersburg on 1 December 1889, and in the United States during the week of 12 January 1890. The median time between the first reported case and peak mortality was five weeks. In Malta, the Asiatic flu took hold between January 1889 and March 1890, with a fatality rate of 4% (39 deaths), and a resurgence in January to May 1892 with 66 fatalities (3.3% case fatality rate). When this flu began, it was debated whether it was in fact a human-to-human contagious disease; its virulence and rapid spread across all climates and terrains demonstrated that it was. There was no standard treatment of flu; quinine and phenazone were used, as well as small doses of strychnine and larger ones of whisky and brandy, and as cheaper treatments linseed, salt and warm water, and glycerin. Many people also thought that fasting would 'starve' the fever, based on the belief that the body would not produce as much heat with less food; this was in fact poor medical advice. Furthermore, many doctors still believed in the miasma theory of disease rather than infectious spread; for example, notable professors of the University of Vienna , Hermann Nothnagel and Otto Kahler considered that the disease was not contagious. US public health departments did little prevention in advance, even though they knew through transoceanic telegraph cable reports, that the Russian influenza was on its way. A result of the Asiatic flu in Malta is that influenza became for the first time a compulsorily notifiable illness. There was no standard treatment of flu; quinine and phenazone were used, as well as small doses of strychnine and larger ones of whisky and brandy, and as cheaper treatments linseed, salt and warm water, and glycerin. Many people also thought that fasting would 'starve' the fever, based on the belief that the body would not produce as much heat with less food; this was in fact poor medical advice. Furthermore, many doctors still believed in the miasma theory of disease rather than infectious spread; for example, notable professors of the University of Vienna , Hermann Nothnagel and Otto Kahler considered that the disease was not contagious. US public health departments did little prevention in advance, even though they knew through transoceanic telegraph cable reports, that the Russian influenza was on its way. A result of the Asiatic flu in Malta is that influenza became for the first time a compulsorily notifiable illness. Researchers have tried for many years to identify the subtypes of Influenza A responsible for the 1889–1890, 1898–1900 and 1918 epidemics. Initially, this work was primarily based on "seroarcheology"—the detection of antibodies to influenza infection in the sera of elderly people—and it was thought that the 1889–1890 pandemic was caused by Influenza A subtype H2, the 1898–1900 epidemic by subtype H3, and the 1918 pandemic by subtype H1. With the confirmation of H1N1 as the cause of the 1918 flu pandemic following identification of H1N1 antibodies in exhumed corpses, reanalysis of seroarcheological data suggested Influenza A subtype H3 (possibly the H3N8 subtype) as a more likely cause for the 1889–1890 pandemic. This view is corroborated by converging seroarcheological and mortality data. In blood sera collected in 1956–1957, birth cohorts likely exposed early in life to the 1889–1890 pandemic had the highest percentages of detectable antibodies against the H3 strain that was later responsible for the 1968 pandemic. Correspondingly, excess mortality decreased sharply during that pandemic for these cohorts, who were 78 years old or older at the time. After the 2002–2004 SARS outbreak , virologists started sequencing human and animal coronaviruses . A comparison of two virus strains in the Betacoronavirus 1 species bovine coronavirus and human coronavirus OC43 indicated that the two had a most recent common ancestor in the late 19th century, with several methods yielding most probable dates around 1890. The authors speculated that an introduction of the former strain to the human population, rather than influenza, might have caused the 1889 epidemic. A Belgian team performed a similar analysis of OC43, identifying a crossover date in the late 1800s. In 2021, examination of contemporary medical reports noted that the pandemic's clinical manifestations resembled those of COVID-19 rather than influenza, with notable similarities including multisystem disease, loss of taste and smell perception, central nervous system symptoms and sequelae similar to long COVID . Other scientists have pointed to the fact the mortality curve for Russian Flu is J-shaped, as found in COVID-19, with little mortality in the very young and high mortality in the old, rather than the U-shaped mortality found in influenza infections, with high mortality in the very young and very old. While a small sample of dental remains has been tested and lends weight to the hypothesis, there is still no scientific consensus that the 1889–1890 outbreak was caused by a coronavirus, with one analysis of the literature suggesting that the evidence for this causality is still "conjectural". Before the first outbreak of Russian influenza, Tomsk province was experiencing an epizootic of pneumonia in cattle. Every year from June to November, up to 13,000 cattle, mostly from the Kulunda steppes, Barnaul district and Semipalatinsk region, were brought to Tomsk for slaughter. In autumn 1889, pneumonia was recorded among cattle in Tomsk. But despite the outbreak, the cattle were not isolated and moved freely through the streets of the city. Meat prices dropped to 1 ruble per pood. Because of the resulting disease, the inhabitants of the city either slaughtered the cattle or sold the animals very cheaply (a cow cost from 5 to 8 rubles). The inhabitants of Siberia hoped that with a drop in temperature the epizootic would subside. The newspapers wrote: "Siberians obediently waited for the onset of cold weather, with the appearance of which, however, the epizootic even more intensified, yes, in addition to it came and obnoxious Influenza. Notes on the relationship between influenza and animal diseases were found in the newspaper "Physician" 1889 г.: "...the connection of influenza with epizootics on horses, dogs and cats is undoubted; these epizootics have much in common with influenza...".These data are in favour of the theory that the "Russian influenza" of 1889 could have been caused by a coronavirus transmitted from cattle to humans. Researchers have tried for many years to identify the subtypes of Influenza A responsible for the 1889–1890, 1898–1900 and 1918 epidemics. Initially, this work was primarily based on "seroarcheology"—the detection of antibodies to influenza infection in the sera of elderly people—and it was thought that the 1889–1890 pandemic was caused by Influenza A subtype H2, the 1898–1900 epidemic by subtype H3, and the 1918 pandemic by subtype H1. With the confirmation of H1N1 as the cause of the 1918 flu pandemic following identification of H1N1 antibodies in exhumed corpses, reanalysis of seroarcheological data suggested Influenza A subtype H3 (possibly the H3N8 subtype) as a more likely cause for the 1889–1890 pandemic. This view is corroborated by converging seroarcheological and mortality data. In blood sera collected in 1956–1957, birth cohorts likely exposed early in life to the 1889–1890 pandemic had the highest percentages of detectable antibodies against the H3 strain that was later responsible for the 1968 pandemic. Correspondingly, excess mortality decreased sharply during that pandemic for these cohorts, who were 78 years old or older at the time. After the 2002–2004 SARS outbreak , virologists started sequencing human and animal coronaviruses . A comparison of two virus strains in the Betacoronavirus 1 species bovine coronavirus and human coronavirus OC43 indicated that the two had a most recent common ancestor in the late 19th century, with several methods yielding most probable dates around 1890. The authors speculated that an introduction of the former strain to the human population, rather than influenza, might have caused the 1889 epidemic. A Belgian team performed a similar analysis of OC43, identifying a crossover date in the late 1800s. In 2021, examination of contemporary medical reports noted that the pandemic's clinical manifestations resembled those of COVID-19 rather than influenza, with notable similarities including multisystem disease, loss of taste and smell perception, central nervous system symptoms and sequelae similar to long COVID . Other scientists have pointed to the fact the mortality curve for Russian Flu is J-shaped, as found in COVID-19, with little mortality in the very young and high mortality in the old, rather than the U-shaped mortality found in influenza infections, with high mortality in the very young and very old. While a small sample of dental remains has been tested and lends weight to the hypothesis, there is still no scientific consensus that the 1889–1890 outbreak was caused by a coronavirus, with one analysis of the literature suggesting that the evidence for this causality is still "conjectural". Before the first outbreak of Russian influenza, Tomsk province was experiencing an epizootic of pneumonia in cattle. Every year from June to November, up to 13,000 cattle, mostly from the Kulunda steppes, Barnaul district and Semipalatinsk region, were brought to Tomsk for slaughter. In autumn 1889, pneumonia was recorded among cattle in Tomsk. But despite the outbreak, the cattle were not isolated and moved freely through the streets of the city. Meat prices dropped to 1 ruble per pood. Because of the resulting disease, the inhabitants of the city either slaughtered the cattle or sold the animals very cheaply (a cow cost from 5 to 8 rubles). The inhabitants of Siberia hoped that with a drop in temperature the epizootic would subside. The newspapers wrote: "Siberians obediently waited for the onset of cold weather, with the appearance of which, however, the epizootic even more intensified, yes, in addition to it came and obnoxious Influenza. Notes on the relationship between influenza and animal diseases were found in the newspaper "Physician" 1889 г.: "...the connection of influenza with epizootics on horses, dogs and cats is undoubted; these epizootics have much in common with influenza...".These data are in favour of the theory that the "Russian influenza" of 1889 could have been caused by a coronavirus transmitted from cattle to humans. Unlike most influenza pandemics such as the 1918 flu, primarily elderly people died in 1889. Due to generally lower standards of living, worse hygiene, and poorer standard of medicine, the proportion of vulnerable people was higher than in the modern world.

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Pandemic influenza

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2009 swine flu pandemic vaccine

The 2009 swine flu pandemic vaccines were influenza vaccines developed to protect against the pandemic H1N1/09 virus . These vaccines either contained inactivated (killed) influenza virus, or weakened live virus that could not cause influenza. The killed virus was injected, while the live virus was given as a nasal spray. Both these types of vaccine were produced by growing the virus in chicken eggs. Around three billion doses were produced, with delivery in November 2009. [ needs update ] In studies, the vaccine [ which? ] appeared both effective and safe, providing a strong protective immune response and having a similar safety profile to the usual seasonal influenza vaccine. However, about 30% of people already had some immunity to the virus, with the vaccine conferring greatest benefit on young people, since many older people are already immune through exposure to similar viruses in the past. The vaccine also provided some cross-protection against the 1918 flu pandemic strain. Early results (pre-25 December 2009) from an observational cohort of 248,000 individuals in Scotland showed the vaccine to be effective at preventing H1N1 influenza (95.0% effectiveness [95% confidence intervals 76.0–100.0%]) and influenza-related hospital admissions (64.7% [95% confidence intervals 12.0–85.8%]). Developing, testing, and manufacturing sufficient quantities of a vaccine is a process that takes many months. According to Keiji Fukuda of the World Health Organization , "There's much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world's population for influenza." The nasal mist version of the vaccine started shipping on 1 October 2009. [ needs update ]Two types of influenza vaccines were available: TIV works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies; while LAIV works by inoculating the body with those same three strains, but in a modified form that cannot cause illness. LAIV is not recommended for individuals under age 2 or over age 49, but might be comparatively more effective among children over age two. For the inactivated vaccines, the virus is grown by injecting it, along with some antibiotics , into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine. The virus replicates within the allantois of the embryo, which is the equivalent of the placenta in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration or centrifugation . The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus into particles, and the broken capsule segments and released proteins are concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline ready for injection. This vaccine mainly contains the killed virus but might also contain tiny amounts of egg protein and the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad , an adjuvant is also added, this contains squalene , vitamin E and an emulsifier called polysorbate 80 . To make the live vaccine, the virus is first adapted to grow at 25 °C (77 °F) and then grown at this temperature until it loses the ability to cause illness in humans, which requires the virus to grow at normal human body temperature of 37 °C (99 °F) . Multiple mutations are needed for the virus to grow at cold temperatures, so this process is effectively irreversible and once the virus has lost virulence (become "attenuated"), it will not regain the ability to infect people. The attenuated virus is then grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate , potassium phosphate , gelatin , the antibiotic gentamicin , and sugar. A different method of producing influenza virus was used to produce the Novartis vaccine Optaflu . In this vaccine the virus is grown in cell culture instead of in eggs. This method is faster than the classic egg-based system and produces a purer final product. There are no traces of egg proteins in the final product, so it is safe for people with egg allergies. Prior to the H1N1/09 outbreak, WHO recommended that vaccines for the Northern Hemisphere's 2009–2010 flu season contain an A(H1N1) -like virus, and stocks were made available. However, the strain of H1N1 in the seasonal flu vaccine was different from the pandemic strain H1N1/09 and offered no immunity against it. The US Centers for Disease Control and Prevention (CDC) characterized over 80 new H1N1 viruses that may be used in a vaccine. There was concern in mid-2009 that, should a second, deadlier wave of this new H1N1 strain appear during the northern autumn of 2009, producing pandemic vaccines ahead of time could turn out to be a serious waste of resources as the vaccine might not be effective against it, and there would also be a shortage of seasonal flu vaccine available if production facilities were switched to the new vaccine. Seasonal flu vaccine was being made as of May 2009. Although vaccine makers would be ready to switch to making a swine flu vaccine, many questions remained unanswered, including: "Should we really make a swine flu vaccine? Should we base a vaccine on the current virus, since flu viruses change rapidly? Vaccine against the current virus might be far less effective against a changed virus – should we wait to see if the virus changes? If vaccine production doesn't start soon, swine flu vaccine won't be ready when it's needed." The costs of producing a vaccine also became an issue, with some U.S. lawmakers questioning whether a new vaccine was worth the unknown benefits. Representatives Phil Gingrey and Paul Broun , for instance, were not convinced that the U.S. should spend up to US$2 billion to produce one, with Gingrey stating "We can't let all of our spending and our reaction be media-driven in responding to a panic so that we don't get Katrina-ed. ... It's important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used – that is a very important decision that our country has to make." In fact, a Fairleigh Dickinson University PublicMind poll found in October 2009 that a majority (62%) of New Jerseyans were not planning on getting the vaccine at all. Before the pandemic was declared, the WHO said that if a pandemic was declared it would attempt to make sure that a substantial amount of vaccine was available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, would be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made" for a pandemic strain. The global body stated that it wanted companies to donate at least 10% of their production or offer reduced prices for poor countries that could otherwise be left without vaccines if there is a sudden surge in demand. Gennady Onishchenko , Russia's chief doctor, said on 2 June 2009 that swine flu was not aggressive enough to cause a worldwide pandemic, noting that the current mortality rate of confirmed cases was 1.6% in Mexico and only 0.1% in the United States. He stated at a press conference, "So far it is unclear if we need to use vaccines against the flu because the virus that is now circulating throughout Europe and North America does not have a pandemic nature." In his opinion, a vaccine could be produced, but said that preparing a vaccine now would be considered "practice," since the world would soon need a new vaccine against a new virus. "What's 16,000 sick people? During any flu season, some 10,000 a day become ill in Moscow alone," he said. After a meeting with the WHO on 14 May 2009, pharmaceutical companies said they were ready to begin making a swine flu vaccine. According to news reports, the WHO's experts would present recommendations to WHO Director-General Margaret Chan, who was expected to issue advice to vaccine manufacturers and the Sixty-second World Health Assembly. WHO's Keiji Fukuda told reporters "These are enormously complicated questions, and they are not something that anyone can make in a single meeting." Most flu vaccine companies can not make both seasonal flu vaccine and pandemic flu vaccine at the same time. Production takes months and it is impossible to switch halfway through if health officials make a mistake. If the swine flu mutates, scientists aren't sure how effective a vaccine made now from the current strain will remain. Rather than wait on the WHO decision, however, some countries in Europe have decided to go ahead with early vaccine orders. On 20 May 2009, AP reported: "Manufacturers won't be able to start making the [swine flu] vaccine until mid-July at the earliest, weeks later than previous predictions, according to an expert panel convened by WHO. It will then take months to produce the vaccine in large quantities. The swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the 'seed stock' from the virus [...] In any case, mass producing a pandemic vaccine would be a gamble, as it would take away manufacturing capacity for the seasonal flu vaccine for the flu that kills up to 500,000 people each year. Some experts have wondered whether the world really needs a vaccine for an illness that so far appears mild." Another option proposed by the CDC was an "earlier rollout of seasonal vaccine," according to the CDC's Daniel Jernigan. He said the CDC would work with vaccine manufacturers and experts to see if that would be possible and desirable. Flu vaccination usually starts in September in the United States and peaks in November. Some vaccine experts agree it would be better to launch a second round of vaccinations against the new H1N1 strain instead of trying to add it to the seasonal flu vaccine or replacing one of its three components with the new H1N1 virus. The Australian company CSL said that they were developing a vaccine for the swine flu and predicted that a suitable vaccine would be ready by August. However, John Sterling, Editor in Chief of Genetic Engineering & Biotechnology News , said on 2 June, "It can take five or six months to come up with an entirely novel influenza vaccine. There is a great deal of hope that biotech and pharma companies might be able to have something ready sooner." As of September 2009 [ update ] a vaccine for H1N1/09 was expected to be available starting in November 2009, with production of three billion doses per year. It was expected that two doses would be needed to provide sufficient protection, but tests indicated that one dose would be sufficient for adults. As of 28 September 2009 [ update ] GlaxoSmithKline produced a vaccine made by growing the virus in hens' eggs, then breaking and deactivating the virus, and Baxter International produced a vaccine made in cell culture, suitable for those who have an egg allergy. The vaccines have been approved for use in the European Union . Initial Phase I human testing began with Novartis ' MF59 candidate in July 2009, at which time phase II trials of CSL's candidate CSL425 vaccine were planned to start in August 2009, but had not begun recruiting. Sanofi Pasteur 's candidate inactivated H1N1 had several phase II trials planned as of 21 July 2009 [ update ] , but had not begun recruiting. News coverage conflicted with this information, as Australian trials of the CSL candidate were announced as having started on 21 July, and the Chinese government announced the start of trials of the Hualan Biological Engineering candidate. Pandemrix , made by GlaxoSmithKline (GSK), and Focetria , made by Novartis were approved by the European Medicines Agency on 25 September 2009, and Celvapan , made by Baxter was approved the following week. The first comparative clinical study of both vaccines started on children in the United Kingdom on 25 September 2009. [ citation needed ] GSK announced results from clinical trials assessing the use of Pandemrix in children, adults, and the elderly. A 2009 trial examined the safety and efficacy of two different doses of the split-virus vaccine , and was published in The New England Journal of Medicine . The vaccine used in the trial was prepared by CSL Biotherapies in chicken eggs, in the same way as the seasonal vaccine. A robust immune response was produced in over 90% of patients after a single dose of either 15 or 30 μg of antigen. This study suggested that the current recommendation for two doses of vaccine are overkill and that a single dose is quite sufficient. Arepanrix , an AS03 - Adjuvanted H1N1 Pandemic Influenza Vaccine similar to Pandemrix and also made by GSK, was authorized by Canada's Minister of Health on 21 October 2009. There was concern in mid-2009 that, should a second, deadlier wave of this new H1N1 strain appear during the northern autumn of 2009, producing pandemic vaccines ahead of time could turn out to be a serious waste of resources as the vaccine might not be effective against it, and there would also be a shortage of seasonal flu vaccine available if production facilities were switched to the new vaccine. Seasonal flu vaccine was being made as of May 2009. Although vaccine makers would be ready to switch to making a swine flu vaccine, many questions remained unanswered, including: "Should we really make a swine flu vaccine? Should we base a vaccine on the current virus, since flu viruses change rapidly? Vaccine against the current virus might be far less effective against a changed virus – should we wait to see if the virus changes? If vaccine production doesn't start soon, swine flu vaccine won't be ready when it's needed." The costs of producing a vaccine also became an issue, with some U.S. lawmakers questioning whether a new vaccine was worth the unknown benefits. Representatives Phil Gingrey and Paul Broun , for instance, were not convinced that the U.S. should spend up to US$2 billion to produce one, with Gingrey stating "We can't let all of our spending and our reaction be media-driven in responding to a panic so that we don't get Katrina-ed. ... It's important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used – that is a very important decision that our country has to make." In fact, a Fairleigh Dickinson University PublicMind poll found in October 2009 that a majority (62%) of New Jerseyans were not planning on getting the vaccine at all. Before the pandemic was declared, the WHO said that if a pandemic was declared it would attempt to make sure that a substantial amount of vaccine was available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, would be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made" for a pandemic strain. The global body stated that it wanted companies to donate at least 10% of their production or offer reduced prices for poor countries that could otherwise be left without vaccines if there is a sudden surge in demand. Gennady Onishchenko , Russia's chief doctor, said on 2 June 2009 that swine flu was not aggressive enough to cause a worldwide pandemic, noting that the current mortality rate of confirmed cases was 1.6% in Mexico and only 0.1% in the United States. He stated at a press conference, "So far it is unclear if we need to use vaccines against the flu because the virus that is now circulating throughout Europe and North America does not have a pandemic nature." In his opinion, a vaccine could be produced, but said that preparing a vaccine now would be considered "practice," since the world would soon need a new vaccine against a new virus. "What's 16,000 sick people? During any flu season, some 10,000 a day become ill in Moscow alone," he said. After a meeting with the WHO on 14 May 2009, pharmaceutical companies said they were ready to begin making a swine flu vaccine. According to news reports, the WHO's experts would present recommendations to WHO Director-General Margaret Chan, who was expected to issue advice to vaccine manufacturers and the Sixty-second World Health Assembly. WHO's Keiji Fukuda told reporters "These are enormously complicated questions, and they are not something that anyone can make in a single meeting." Most flu vaccine companies can not make both seasonal flu vaccine and pandemic flu vaccine at the same time. Production takes months and it is impossible to switch halfway through if health officials make a mistake. If the swine flu mutates, scientists aren't sure how effective a vaccine made now from the current strain will remain. Rather than wait on the WHO decision, however, some countries in Europe have decided to go ahead with early vaccine orders. On 20 May 2009, AP reported: "Manufacturers won't be able to start making the [swine flu] vaccine until mid-July at the earliest, weeks later than previous predictions, according to an expert panel convened by WHO. It will then take months to produce the vaccine in large quantities. The swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the 'seed stock' from the virus [...] In any case, mass producing a pandemic vaccine would be a gamble, as it would take away manufacturing capacity for the seasonal flu vaccine for the flu that kills up to 500,000 people each year. Some experts have wondered whether the world really needs a vaccine for an illness that so far appears mild." Another option proposed by the CDC was an "earlier rollout of seasonal vaccine," according to the CDC's Daniel Jernigan. He said the CDC would work with vaccine manufacturers and experts to see if that would be possible and desirable. Flu vaccination usually starts in September in the United States and peaks in November. Some vaccine experts agree it would be better to launch a second round of vaccinations against the new H1N1 strain instead of trying to add it to the seasonal flu vaccine or replacing one of its three components with the new H1N1 virus. The Australian company CSL said that they were developing a vaccine for the swine flu and predicted that a suitable vaccine would be ready by August. However, John Sterling, Editor in Chief of Genetic Engineering & Biotechnology News , said on 2 June, "It can take five or six months to come up with an entirely novel influenza vaccine. There is a great deal of hope that biotech and pharma companies might be able to have something ready sooner." As of September 2009 [ update ] a vaccine for H1N1/09 was expected to be available starting in November 2009, with production of three billion doses per year. It was expected that two doses would be needed to provide sufficient protection, but tests indicated that one dose would be sufficient for adults. As of 28 September 2009 [ update ] GlaxoSmithKline produced a vaccine made by growing the virus in hens' eggs, then breaking and deactivating the virus, and Baxter International produced a vaccine made in cell culture, suitable for those who have an egg allergy. The vaccines have been approved for use in the European Union . Initial Phase I human testing began with Novartis ' MF59 candidate in July 2009, at which time phase II trials of CSL's candidate CSL425 vaccine were planned to start in August 2009, but had not begun recruiting. Sanofi Pasteur 's candidate inactivated H1N1 had several phase II trials planned as of 21 July 2009 [ update ] , but had not begun recruiting. News coverage conflicted with this information, as Australian trials of the CSL candidate were announced as having started on 21 July, and the Chinese government announced the start of trials of the Hualan Biological Engineering candidate. Pandemrix , made by GlaxoSmithKline (GSK), and Focetria , made by Novartis were approved by the European Medicines Agency on 25 September 2009, and Celvapan , made by Baxter was approved the following week. The first comparative clinical study of both vaccines started on children in the United Kingdom on 25 September 2009. [ citation needed ] GSK announced results from clinical trials assessing the use of Pandemrix in children, adults, and the elderly. A 2009 trial examined the safety and efficacy of two different doses of the split-virus vaccine , and was published in The New England Journal of Medicine . The vaccine used in the trial was prepared by CSL Biotherapies in chicken eggs, in the same way as the seasonal vaccine. A robust immune response was produced in over 90% of patients after a single dose of either 15 or 30 μg of antigen. This study suggested that the current recommendation for two doses of vaccine are overkill and that a single dose is quite sufficient. Arepanrix , an AS03 - Adjuvanted H1N1 Pandemic Influenza Vaccine similar to Pandemrix and also made by GSK, was authorized by Canada's Minister of Health on 21 October 2009. A review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 ("swine flu") vaccine has a safety profile similar to that of seasonal vaccine. In an initial clinical trial in Australia, non-serious adverse events were reported by about half of the 240 people vaccinated, with these events including tenderness and pain at the site of injection, headache, malaise, and muscle pain. Two people had more severe events, with a much longer spell of nausea, muscle pain and malaise that lasted several days. The authors stated that the frequency and severity of these adverse events were similar to those normally seen with seasonal influenza vaccines. A second trial involved 2,200 people ranging from 3 to 77 years of age. In this study no patients reported serious adverse events, with the most commonly observed events being pain at the injection site and fever, which occurred in 10–25% of people. Although this trial followed up patients individually, the Government has been criticized for relying on voluntary reporting for post-vaccination evaluation in other circumstances, since this is "unlikely to accurately measure the percentage of people who get adverse effect". As of 19 November 2009 [ update ] , the World Health Organization (WHO) said that 65 million doses of vaccine had been administered and that it had a similar safety profile to the seasonal flu vaccine, with no significant differences in the adverse events produced by the different types of vaccine. There has been one report of an adverse event per 10,000 doses of vaccine, with only five percent of these adverse events being serious, an overall rate of serious events of one in 200,000 doses. In Canada, after 6.6 million doses of vaccine had been distributed between 21 October and 7 November, there were reports of mild adverse events in 598 people vaccinated including: nausea, dizziness, headache, fever, vomiting, and swelling or soreness at the injection site. There were reports of tingling lips or tongue, difficulty breathing, hives, and skin rashes. Thirty six people had serious adverse events, including anaphylaxis and febrile convulsions. The rate of serious adverse events is one in 200,000 doses distributed, which according to Canada's chief public health officer, is less than expected for the seasonal flu vaccine. GlaxoSmithKline recalled a batch of vaccine in Canada after it appeared to cause higher rates of adverse events than other batches. In the USA 46 million doses had been distributed as of 20 November 2009 [ update ] and 3182 adverse events were reported. The CDC stated that the "vast majority" were mild, with about one serious adverse event in 260,000 doses. In Japan around 15 million people had been vaccinated by 31 December 2009. 1,900 cases of side effects and 104 cases of death were reported from medical institutions. The health ministry announced that it will conduct epidemiologic investigation. In France, around five million people had been vaccinated by 30 December 2009. 2,657 cases of side effects, eight cases of intrauterine death and five cases of miscarriages were reported after vaccination by afssaps . Rare potential adverse events are temporary bleeding disorders and Guillain–Barré syndrome (GBS), a serious condition involving the peripheral nervous system , from which most patients recover fully within a few months to a year. Some studies have indicated that influenza-like illness is itself associated with an increased risk of GBS, suggesting that vaccination might indirectly protect against the disorder by protecting against flu. According to Marie-Paule Kieny of WHO assessing the side-effects of large-scale influenza vaccination is complicated by the fact that in any large population a few people will become ill and die at any time. For example, in any six-week period in the UK six sudden deaths from unknown causes and 22 cases of Guillain–Barré syndrome would be expected, so if everyone in the UK were vaccinated, this background rate of illness and death would continue as normal and some people would die simply by chance soon after the vaccination. Some scientists have reported concerns about the longer-term effects of the vaccine. For instance, Sucharit Bhakdi , professor of medical microbiology at the Johannes Gutenberg University of Mainz in Germany, wrote in the journal, Medical Microbiology and Immunology , of the possibility that immune stimulation by vaccines or any other cause might worsen pre-existing heart disease. Chris Shaw, a neuroscientist at the University of British Columbia, expressed concern that serious side-effects may not appear immediately; he said it took five to ten years to see most of the Gulf War syndrome outcomes. The CDC states that most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in The New England Journal of Medicine covering close to 100 million doses of H1N1 flu vaccine found only eleven cases of Guillain–Barré syndrome , actually lower than the normal rate of the disease in China, and no other notable side effects. A 2009 review of the use of influenza vaccines in pregnant women stated that influenza infections posed a major risk during pregnancy and that multiple studies had shown that the inactivated vaccine was safe in pregnant women, concluding that this vaccine "can be safely and effectively administered during any trimester of pregnancy" and that high levels of immunization would avert "a significant number of deaths". A 2004 review of the safety of influenza vaccines in children stated that the live vaccine had been shown to be safe but that it might trigger wheezing in some children with asthma; less data for the trivalent inactivated vaccine was available, but no serious symptoms had been seen in clinical trials. Newsweek states that "wild rumours" about the swine flu vaccine are being spread through e-mails, it writes that "The claims are nearly pure bunk, with only trace amounts of fact." These rumours generally make unfounded claims that the vaccine is dangerous and they may also promote conspiracy theories . For example, Newsweek states that some chain e-mails make false claims about squalene (shark liver oil) in vaccines. The New York Times also notes that anti-vaccine groups have spread "dire warnings" about formulations of the vaccine that contain squalene as an adjuvant . An adjuvant is a substance that boosts the body's immune response, thereby stretching the supply of the vaccine and helping immunize elderly people with a weak immune system. Squalene is a normal part of the human body, made in the liver and circulating in the blood, and is also found in many foods, such as eggs and olive oil . None of the formulations of vaccine used in the US contain squalene, or any other adjuvant. However, some European and Canadian formulations do contain 25 μg of squalene per dose, which is roughly the amount found in a drop of olive oil. Some animal experiments have suggested that squalene might be linked to autoimmune disorders. although others suggest squalene might protect people against cancer. Squalene-based adjuvants have been used in European influenza vaccines since 1997, with about 22 million doses administered over the past twelve years. The WHO states that no severe side effects have been associated with these vaccines, although they can produce mild inflammation at the site of injection. The safety of squalene-containing influenza vaccines have also been tested in two separate clinical trials, one with healthy non-elderly people, and one with elderly people, in both trials the vaccine was safe and well tolerated, with only weak side-effects, such as mild pain at the injection site. A 2009 meta-analysis brought together data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvanted vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the normal rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines". A 2004 review of the effects of adjuvants on mice and humans concluded that "despite numerous case reports on vaccination induced autoimmunity, most epidemiological studies failed to confirm the association and the risk appears to be extremely low or non-existent", although the authors noted that the possibility that adjuvants might cause damaging immune reactions in a few susceptible people has not been completely ruled out. A 2009 review of oil-based adjuvants in influenza vaccines stated that this type of adjuvant "neither stimulates antibodies against squalene oil naturally produced by the humans body nor enhances titers of preexisting antibodies to squalene" and that these formulations did not raise any safety concerns. A paper published in 2000 suggested that squalene might have caused of Gulf War syndrome by producing anti-squalene antibodies, although other scientists stated that it was uncertain if the methods used were actually capable of detecting these antibodies. A 2009 U.S. Department of Defense study comparing healthy Navy personnel to those suffering from Gulf War syndrome was published in the journal Vaccine , this used a validated test for these antibodies and found no link between the presence of the antibodies and illness, with about half of both groups having these antibodies and no correlation between symptoms and antibodies. Furthermore, none of the vaccines given to US troops during the Gulf war actually contained any squalene adjuvants. Multi-dose versions of the vaccine contain the preservative thiomersal (also known as thimerosal), a mercury compound that prevents contamination when the vial is used repeatedly. Single-dose versions and the live vaccine do not contain this preservative. In the U.S., one dose from a multi-dose vial contains approximately 25 micrograms of mercury, a bit less than a typical tuna fish sandwich . (The comparison of the injected and ingested quantities is for reference only, since the rate of absorption of ingested elemental mercury into the bloodstream is less than 0.01%. ) In Canada, different variants contain five and 50 micrograms of thimerosal per dose. The use of thiomersal has been controversial , with claims that it can cause autism and other developmental disorders . The U.S. Institute of Medicine examined these claims and concluded in 2004 that the evidence did not support any link between vaccines and autism. Other reviews came to similar conclusions, with a 2006 review in the Canadian Journal of Neurological Sciences stating that there is no convincing evidence to support the claim that thimerosal has a causal role in autism, and a 2009 review in the journal Clinical Infectious Diseases stating that claims that mercury can cause autism are "biologically implausible". The U.K. National Health Service stated in 2003 that "There is no evidence of long-term adverse effects due to the exposure levels of thiomersal in vaccines." The World Health Organization concluded that there is "no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines". In 2008 a review noted that even though thiomersal was removed from all US childhood vaccines in 2001, this has not changed the number of autism diagnoses, which are still increasing. According to the CDC, there is no evidence either for or against dystonia being caused by the vaccinations. Dystonia is extremely rare. Due to the very low numbers of cases, dystonia is poorly understood. There were only five cases noted that might have been associated with influenza vaccinations over a span of eighteen years. In one discredited case, a woman wrongly blamed difficulties with movement and speech on a seasonal influenza vaccination. The Dystonia Medical Research Foundation stated that it is unlikely that the symptoms in this case were actually dystonia and stated that there has "never been a validated case of dystonia resulting from a flu shot". A vaccine court special master concluded that the woman's symptoms weren't from the vaccine. Additionally, the woman later said that Jenny McCarthy's anti-vaccine group Generation Rescue had "commandeered my injury to turn it into a poster story for their cause against vaccines." On 15 December 2009, one of the five manufacturers supplying the H1N1 vaccine to the United States recalled thousands of doses because they were not as potent as expected. The French manufacturer Sanofi Pasteur voluntarily recalled about 800,000 doses of vaccine meant for children between the ages of six months and 35 months. The company and the Centers for Disease Control and Prevention (CDC) emphasized that the recall was not prompted by safety concerns, and that even though the vaccine is not quite as potent as it is supposed to be, children who received it do not need to be immunized again. The CDC emphasized that there is no danger for any child who received the recalled vaccine. When asked what parents should do, CDC spokesman Tom Skinner said, "absolutely nothing." He said if children receive this vaccine, they will be fine. In 2010, The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL) received reports from Swedish and Finnish health care professionals regarding narcolepsy as suspected adverse reaction following Pandemrix flu vaccination. The reports concern children aged 12–16 years where symptoms compatible with narcolepsy , diagnosed after thorough medical investigation, have occurred one to two months after vaccination. [ citation needed ] THL concluded in February 2011 that there is a clear connection between the Pandemrix vaccination campaign of 2009 and 2010 and narcolepsy epidemic in Finland: there was a nine times higher probability to get narcolepsy with vaccination than without it. At the end of March 2011, an MPA press release stated: "Results from a Swedish registry based cohort study indicate a 4-fold increased risk of narcolepsy in children and adolescents below the age of 20 vaccinated with Pandemrix, compared to children of the same age that were not vaccinated." The same study found no increased risk in adults who were vaccinated with Pandemrix. [ citation needed ]A 2009 review of the use of influenza vaccines in pregnant women stated that influenza infections posed a major risk during pregnancy and that multiple studies had shown that the inactivated vaccine was safe in pregnant women, concluding that this vaccine "can be safely and effectively administered during any trimester of pregnancy" and that high levels of immunization would avert "a significant number of deaths". A 2004 review of the safety of influenza vaccines in children stated that the live vaccine had been shown to be safe but that it might trigger wheezing in some children with asthma; less data for the trivalent inactivated vaccine was available, but no serious symptoms had been seen in clinical trials. Newsweek states that "wild rumours" about the swine flu vaccine are being spread through e-mails, it writes that "The claims are nearly pure bunk, with only trace amounts of fact." These rumours generally make unfounded claims that the vaccine is dangerous and they may also promote conspiracy theories . For example, Newsweek states that some chain e-mails make false claims about squalene (shark liver oil) in vaccines. The New York Times also notes that anti-vaccine groups have spread "dire warnings" about formulations of the vaccine that contain squalene as an adjuvant . An adjuvant is a substance that boosts the body's immune response, thereby stretching the supply of the vaccine and helping immunize elderly people with a weak immune system. Squalene is a normal part of the human body, made in the liver and circulating in the blood, and is also found in many foods, such as eggs and olive oil . None of the formulations of vaccine used in the US contain squalene, or any other adjuvant. However, some European and Canadian formulations do contain 25 μg of squalene per dose, which is roughly the amount found in a drop of olive oil. Some animal experiments have suggested that squalene might be linked to autoimmune disorders. although others suggest squalene might protect people against cancer. Squalene-based adjuvants have been used in European influenza vaccines since 1997, with about 22 million doses administered over the past twelve years. The WHO states that no severe side effects have been associated with these vaccines, although they can produce mild inflammation at the site of injection. The safety of squalene-containing influenza vaccines have also been tested in two separate clinical trials, one with healthy non-elderly people, and one with elderly people, in both trials the vaccine was safe and well tolerated, with only weak side-effects, such as mild pain at the injection site. A 2009 meta-analysis brought together data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvanted vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the normal rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines". A 2004 review of the effects of adjuvants on mice and humans concluded that "despite numerous case reports on vaccination induced autoimmunity, most epidemiological studies failed to confirm the association and the risk appears to be extremely low or non-existent", although the authors noted that the possibility that adjuvants might cause damaging immune reactions in a few susceptible people has not been completely ruled out. A 2009 review of oil-based adjuvants in influenza vaccines stated that this type of adjuvant "neither stimulates antibodies against squalene oil naturally produced by the humans body nor enhances titers of preexisting antibodies to squalene" and that these formulations did not raise any safety concerns. A paper published in 2000 suggested that squalene might have caused of Gulf War syndrome by producing anti-squalene antibodies, although other scientists stated that it was uncertain if the methods used were actually capable of detecting these antibodies. A 2009 U.S. Department of Defense study comparing healthy Navy personnel to those suffering from Gulf War syndrome was published in the journal Vaccine , this used a validated test for these antibodies and found no link between the presence of the antibodies and illness, with about half of both groups having these antibodies and no correlation between symptoms and antibodies. Furthermore, none of the vaccines given to US troops during the Gulf war actually contained any squalene adjuvants. Multi-dose versions of the vaccine contain the preservative thiomersal (also known as thimerosal), a mercury compound that prevents contamination when the vial is used repeatedly. Single-dose versions and the live vaccine do not contain this preservative. In the U.S., one dose from a multi-dose vial contains approximately 25 micrograms of mercury, a bit less than a typical tuna fish sandwich . (The comparison of the injected and ingested quantities is for reference only, since the rate of absorption of ingested elemental mercury into the bloodstream is less than 0.01%. ) In Canada, different variants contain five and 50 micrograms of thimerosal per dose. The use of thiomersal has been controversial , with claims that it can cause autism and other developmental disorders . The U.S. Institute of Medicine examined these claims and concluded in 2004 that the evidence did not support any link between vaccines and autism. Other reviews came to similar conclusions, with a 2006 review in the Canadian Journal of Neurological Sciences stating that there is no convincing evidence to support the claim that thimerosal has a causal role in autism, and a 2009 review in the journal Clinical Infectious Diseases stating that claims that mercury can cause autism are "biologically implausible". The U.K. National Health Service stated in 2003 that "There is no evidence of long-term adverse effects due to the exposure levels of thiomersal in vaccines." The World Health Organization concluded that there is "no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines". In 2008 a review noted that even though thiomersal was removed from all US childhood vaccines in 2001, this has not changed the number of autism diagnoses, which are still increasing. According to the CDC, there is no evidence either for or against dystonia being caused by the vaccinations. Dystonia is extremely rare. Due to the very low numbers of cases, dystonia is poorly understood. There were only five cases noted that might have been associated with influenza vaccinations over a span of eighteen years. In one discredited case, a woman wrongly blamed difficulties with movement and speech on a seasonal influenza vaccination. The Dystonia Medical Research Foundation stated that it is unlikely that the symptoms in this case were actually dystonia and stated that there has "never been a validated case of dystonia resulting from a flu shot". A vaccine court special master concluded that the woman's symptoms weren't from the vaccine. Additionally, the woman later said that Jenny McCarthy's anti-vaccine group Generation Rescue had "commandeered my injury to turn it into a poster story for their cause against vaccines." On 15 December 2009, one of the five manufacturers supplying the H1N1 vaccine to the United States recalled thousands of doses because they were not as potent as expected. The French manufacturer Sanofi Pasteur voluntarily recalled about 800,000 doses of vaccine meant for children between the ages of six months and 35 months. The company and the Centers for Disease Control and Prevention (CDC) emphasized that the recall was not prompted by safety concerns, and that even though the vaccine is not quite as potent as it is supposed to be, children who received it do not need to be immunized again. The CDC emphasized that there is no danger for any child who received the recalled vaccine. When asked what parents should do, CDC spokesman Tom Skinner said, "absolutely nothing." He said if children receive this vaccine, they will be fine. In 2010, The Swedish Medical Products Agency (MPA) and The Finnish National Institute for Health and Welfare (THL) received reports from Swedish and Finnish health care professionals regarding narcolepsy as suspected adverse reaction following Pandemrix flu vaccination. The reports concern children aged 12–16 years where symptoms compatible with narcolepsy , diagnosed after thorough medical investigation, have occurred one to two months after vaccination. [ citation needed ] THL concluded in February 2011 that there is a clear connection between the Pandemrix vaccination campaign of 2009 and 2010 and narcolepsy epidemic in Finland: there was a nine times higher probability to get narcolepsy with vaccination than without it. At the end of March 2011, an MPA press release stated: "Results from a Swedish registry based cohort study indicate a 4-fold increased risk of narcolepsy in children and adolescents below the age of 20 vaccinated with Pandemrix, compared to children of the same age that were not vaccinated." The same study found no increased risk in adults who were vaccinated with Pandemrix. [ citation needed ]The American Centers for Disease Control and Prevention issued the following recommendations on who should be vaccinated (order is not in priority): Pregnant women, because they are at higher risk of complications and can potentially provide protection to infants who cannot be vaccinated; Household contacts and caregivers for children younger than 6 months of age, because younger infants are at higher risk of influenza-related complications and cannot be vaccinated. Vaccination of those in close contact with infants younger than 6 months old might help protect infants by "cocooning" them from the virus; Healthcare and emergency medical services personnel, because infections among healthcare workers have been reported and this can be a potential source of infection for vulnerable patients. Also, increased absenteeism in this population could reduce healthcare system capacity; All people from 6 months through 24 years of age: Children from 6 months through 18 years of age, because cases of 2009 H1N1 influenza have been seen in children who are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and Young adults 19 through 24 years of age, because many cases of 2009 H1N1 influenza have been seen in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, Persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza. Once the demand for these groups has been met at a local level, everyone from the ages of 25 through 64 years should be vaccinated too. Children from 6 months through 18 years of age, because cases of 2009 H1N1 influenza have been seen in children who are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and Young adults 19 through 24 years of age, because many cases of 2009 H1N1 influenza have been seen in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, In addition, the CDC recommends: Children through 9 years of age should get two doses of vaccine, about a month apart. Older children and adults need only one dose. The UK 's National Health Service policy is to provide vaccine in this order of priority: People aged between six months and 65 years with: chronic lung disease; chronic heart disease; chronic kidney disease; chronic liver disease; chronic neurological disease; diabetes; or suppressed immune system, whether due to disease or treatment. All pregnant women. People who live with someone whose immune system is compromised (for example, people with cancer or HIV/AIDS). People aged 65 and over in the seasonal flu vaccine at-risk groups. chronic lung disease; chronic heart disease; chronic kidney disease; chronic liver disease; chronic neurological disease; diabetes; or suppressed immune system, whether due to disease or treatment. This excludes the large majority of individuals aged six months to 24 years, a group for which the CDC recommends vaccination. The NHS notes that: Healthy people over 65 years of age seem to have some natural immunity. Children, while disproportionately affected, tend to make full recoveries. The vaccine is ineffective in young infants. The United Kingdom began its administration program 21 October 2009. UK Soldiers serving in Afghanistan will also be offered vaccination. By April 2010, it was apparent that most of the vaccine was not needed. The US government had bought 229 million doses of H1N1 vaccines of which 91 million doses were used; of the surplus, 5 million doses were stored in bulk, 15 million doses were sent to developing countries and 71 million doses were destroyed. The World Health Organization is planning to examine if it overreacted to the H1N1 outbreak. The American Centers for Disease Control and Prevention issued the following recommendations on who should be vaccinated (order is not in priority): Pregnant women, because they are at higher risk of complications and can potentially provide protection to infants who cannot be vaccinated; Household contacts and caregivers for children younger than 6 months of age, because younger infants are at higher risk of influenza-related complications and cannot be vaccinated. Vaccination of those in close contact with infants younger than 6 months old might help protect infants by "cocooning" them from the virus; Healthcare and emergency medical services personnel, because infections among healthcare workers have been reported and this can be a potential source of infection for vulnerable patients. Also, increased absenteeism in this population could reduce healthcare system capacity; All people from 6 months through 24 years of age: Children from 6 months through 18 years of age, because cases of 2009 H1N1 influenza have been seen in children who are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and Young adults 19 through 24 years of age, because many cases of 2009 H1N1 influenza have been seen in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, Persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza. Once the demand for these groups has been met at a local level, everyone from the ages of 25 through 64 years should be vaccinated too. Children from 6 months through 18 years of age, because cases of 2009 H1N1 influenza have been seen in children who are in close contact with each other in school and day care settings, which increases the likelihood of disease spread, and Young adults 19 through 24 years of age, because many cases of 2009 H1N1 influenza have been seen in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, In addition, the CDC recommends: Children through 9 years of age should get two doses of vaccine, about a month apart. Older children and adults need only one dose. The UK 's National Health Service policy is to provide vaccine in this order of priority: People aged between six months and 65 years with: chronic lung disease; chronic heart disease; chronic kidney disease; chronic liver disease; chronic neurological disease; diabetes; or suppressed immune system, whether due to disease or treatment. All pregnant women. People who live with someone whose immune system is compromised (for example, people with cancer or HIV/AIDS). People aged 65 and over in the seasonal flu vaccine at-risk groups. chronic lung disease; chronic heart disease; chronic kidney disease; chronic liver disease; chronic neurological disease; diabetes; or suppressed immune system, whether due to disease or treatment. This excludes the large majority of individuals aged six months to 24 years, a group for which the CDC recommends vaccination. The NHS notes that: Healthy people over 65 years of age seem to have some natural immunity. Children, while disproportionately affected, tend to make full recoveries. The vaccine is ineffective in young infants. The United Kingdom began its administration program 21 October 2009. UK Soldiers serving in Afghanistan will also be offered vaccination. By April 2010, it was apparent that most of the vaccine was not needed. The US government had bought 229 million doses of H1N1 vaccines of which 91 million doses were used; of the surplus, 5 million doses were stored in bulk, 15 million doses were sent to developing countries and 71 million doses were destroyed. The World Health Organization is planning to examine if it overreacted to the H1N1 outbreak. General political issues, not restricted to the 2009 outbreak, arose regarding the distribution of vaccine. In many countries supplies are controlled by national or local governments, and the question of how the vaccine will be allocated should there be an insufficient supply for everyone is critical, and will likely depend on the patterns of any pandemic, and the age groups most at risk for serious complications, including death. In the case of a lethal pandemic people will be demanding access to the vaccine and the major problem will be making it available to those who need it. While it has been suggested that compulsory vaccination may be needed to control a pandemic, many countries do not have a legal framework that would allow this. The only populations easily compelled to accept vaccination are military personnel (who can be given routine vaccinations as part of their service obligations), health care personnel (who can be required to be vaccinated to protect patients), and school children, who (under United States constitutional law) could be required to be vaccinated as a condition of attending school.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Flu_season/html

Flu season

Flu season is an annually recurring time period characterized by the prevalence of an outbreak of influenza (flu). The season occurs during the cold half of the year in each hemisphere . It takes approximately two days to show symptoms. Influenza activity can sometimes be predicted and even tracked geographically. While the beginning of major flu activity in each season varies by location, in any specific location these minor epidemics usually take about three weeks to reach its pinnacle, and another three weeks to significantly diminish. Annually, about 3 to 5 million cases of severe illness and 290,000 to 650,000 deaths from seasonal flu occur worldwide. Three virus families, Influenza virus A , B , and C are the main infective agents that cause influenza. During periods of cooler temperature, influenza cases increase roughly tenfold or more. Despite the higher incidence of manifestations of the flu during the season, the viruses are actually transmitted throughout populations all year round. [ citation needed ] Each annual flu season is normally associated with a major influenza virus sub type. The associated sub type changes each year, due to development of immunological resistance to a previous year's strain (through exposure and vaccinations), and mutational changes in previously dormant viruses strains. The exact mechanism behind the seasonal nature of influenza outbreaks is unknown. Some proposed explanations are: Research in guinea pigs has shown that the aerosol transmission of the virus is enhanced when the air is cold and dry. The dependence on aridity appears to be due to degradation of the virus particles in moist air, while the dependence on cold appears to be due to infected hosts shedding the virus for a longer period of time. The researchers did not find that the cold impaired the immune response of the guinea pigs to the virus. [ citation needed ] Research done by the National Institute of Child Health and Human Development (NICHD) in 2008 found that the influenza virus has a butter-like coating. The coating melts when it enters the respiratory tract. In the winter, the coating becomes a hardened shell; therefore, it can survive in the cold weather similar to a spore. In the summer, the coating melts before the virus reaches the respiratory tract. In the United States , the flu season is considered October through May. It typically reaches an apex in February, with a seasonal baseline varying between 6.1% and 7.7% of all deaths. In Australia , the flu season is considered May to October. It usually peaks in August. For other southern hemisphere countries such as Argentina , Chile , South Africa , and Paraguay also tend to start around June. Brazil has a complex seasonality component for its flu season, due to part of its being in a tropical climate, but its further south latitudes have their flu peaks in June–July, during the southern hemisphere winters. Flu seasons also exist in the tropics and subtropics , with variability from region to region. In Hong Kong , which has a humid subtropical climate , the flu season runs from December to March, in the winter and early spring. Flu vaccinations are used to diminish the effects of the flu season and can lower an individual's risk of getting the flu by about half. Since the Northern and Southern Hemisphere have winter at different times of the year, there are actually two flu seasons each year. Therefore, the World Health Organization (assisted by the National Influenza Centers ) recommends two vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere. According to the U.S. Department of Health, a growing number of large companies provide their employees with seasonal flu shots, either at a small cost to the employee or as a free service. The annually updated trivalent influenza vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2 , H1N1 , and B influenza viruses. The dominant strain in January 2006 was H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. Medical conditions that compromise the immune system increase the risks from flu. [ citation needed ] Millions of people have diabetes . When blood sugars are not well controlled, diabetics can quickly develop a wide range of complications. Diabetes results in elevated blood sugars in the body, and this environment allows viruses and bacteria to thrive. [ citation needed ] If blood sugars are poorly controlled, a mild flu can quickly turn severe, leading to hospitalization and even death . Uncontrolled blood sugars suppresses the immune systems and generally lead to more severe cases of the common cold or influenza. Thus, it has been recommended that diabetics be vaccinated against flu, before the start of the flu season. The CDC recommends that people with asthma and chronic obstructive pulmonary disease (COPD) be vaccinated against flu before the flu season. People with asthma can develop life-threatening complications from influenza and the common cold viruses. Some of these complications include pneumonias , acute bronchitis , and acute respiratory distress syndrome . Each year flu related complications in the USA affect close to 100,000 asthmatics, and millions more are seen in the emergency room because of severe shortness of breath . The CDC recommends that asthmatics are vaccinated between October and November, before the peak of the flu season. Flu vaccines take about two weeks to become effective. People with cancer usually have a suppressed immune system . Moreover, many cancer patients undergo radiation therapy and potent immunosuppressive medications, which further suppresses the body's ability to fight off infections. Everyone with cancer is highly susceptible and is at risk for complications from flu. People with cancer or a history of cancer should receive the seasonal flu shot. Flu vaccination is also strict for lung cancer patients, as cancer leads to complications of pneumonia and bronchitis. People with cancer should not receive the nasal spray vaccine. The flu shot is made up of inactivated (killed) viruses, and the nasal spray vaccines are made up of live viruses. The flu shot is safer for those with a weakened immune system. Those who have received cancer treatment such as chemotherapy and/or radiation therapy within the last month, or have a blood or lymphatic form of cancer should call their doctor immediately if they suspect they may have flu. Individuals who have HIV/AIDS are prone to a variety of infections. HIV weakens the body's immune system, leaving them vulnerable to viral, bacterial, fungal, and protozoa disorders. People with HIV are at an increased risk of serious flu-related complications. Many reports have shown that individuals with HIV can develop serious pneumonias that need hospitalization and aggressive antibiotic therapy. Moreover, people with HIV have a longer flu season and are at a high risk of death. Vaccination with the flu shot has been shown to boost the immune system and protect against the seasonal flu in some patients with HIV. Millions of people have diabetes . When blood sugars are not well controlled, diabetics can quickly develop a wide range of complications. Diabetes results in elevated blood sugars in the body, and this environment allows viruses and bacteria to thrive. [ citation needed ] If blood sugars are poorly controlled, a mild flu can quickly turn severe, leading to hospitalization and even death . Uncontrolled blood sugars suppresses the immune systems and generally lead to more severe cases of the common cold or influenza. Thus, it has been recommended that diabetics be vaccinated against flu, before the start of the flu season. The CDC recommends that people with asthma and chronic obstructive pulmonary disease (COPD) be vaccinated against flu before the flu season. People with asthma can develop life-threatening complications from influenza and the common cold viruses. Some of these complications include pneumonias , acute bronchitis , and acute respiratory distress syndrome . Each year flu related complications in the USA affect close to 100,000 asthmatics, and millions more are seen in the emergency room because of severe shortness of breath . The CDC recommends that asthmatics are vaccinated between October and November, before the peak of the flu season. Flu vaccines take about two weeks to become effective. People with cancer usually have a suppressed immune system . Moreover, many cancer patients undergo radiation therapy and potent immunosuppressive medications, which further suppresses the body's ability to fight off infections. Everyone with cancer is highly susceptible and is at risk for complications from flu. People with cancer or a history of cancer should receive the seasonal flu shot. Flu vaccination is also strict for lung cancer patients, as cancer leads to complications of pneumonia and bronchitis. People with cancer should not receive the nasal spray vaccine. The flu shot is made up of inactivated (killed) viruses, and the nasal spray vaccines are made up of live viruses. The flu shot is safer for those with a weakened immune system. Those who have received cancer treatment such as chemotherapy and/or radiation therapy within the last month, or have a blood or lymphatic form of cancer should call their doctor immediately if they suspect they may have flu. Individuals who have HIV/AIDS are prone to a variety of infections. HIV weakens the body's immune system, leaving them vulnerable to viral, bacterial, fungal, and protozoa disorders. People with HIV are at an increased risk of serious flu-related complications. Many reports have shown that individuals with HIV can develop serious pneumonias that need hospitalization and aggressive antibiotic therapy. Moreover, people with HIV have a longer flu season and are at a high risk of death. Vaccination with the flu shot has been shown to boost the immune system and protect against the seasonal flu in some patients with HIV. The cost of a flu season in lives lost, medical expenses and economic impact can be severe. In 2017, the World Health Organization (WHO) estimated that the seasonal flu causes 290,000 to 650,000 annual deaths worldwide. In 2003, the WHO estimated that the cost of flu epidemics in the United States was US$71–167 billion per year. A 2007 study found that annual influenza epidemics in the US result in approximately 600,000 life-years lost , 3 million hospitalized days, and 30 million outpatient visits, resulting in medical costs of $10 billion annually. According to this study, lost earnings due to illness and loss of life amounted to over $15 billion annually and the total economic burden of annual influenza epidemics amounts to over $80 billion. Also, in the US the flu season usually accounts for 200,000 hospitalizations and 41,000 deaths. [ citation needed ] Because the mortality rate of the H1N1 swine flu is lower than that of common flu strains, this [ clarification needed ] number was actually lower in 2009. According to an article in Clinical Infectious Diseases , published in 2011, the estimated health burden of 2009 Pandemic Influenza A (H1N1), between April 2009 to April 2010, was "approximately 60.8 million cases (range: 43.3–89.3 million), 274,304 hospitalizations (195,086–402,719), and 12,469 deaths (8,868–18,306)" "in the United States due to pH1N1." Seasonal epidemics of influenza can be severe. Some can even rival pandemics in terms of excess mortality. In fact, it is not so much mortality that distinguishes seasonal epidemics from pandemics but rather the extent to which the disease has spread, though the reasons behind this distinction between epidemic and pandemic, as well as the geographic variability observed within individual flu seasons, remain poorly understood. As such, some flu seasons are particularly notable in terms of severity. Others are notable due to other unique or unusual factors, as described below. According to the United States Public Health Service , "The epidemic of 1928–1929 was the most important since that of 1920", itself considered to be the final wave, at least in the US, of the 1918 pandemic . There were approximately 50,000 excess influenza and pneumonia deaths in the country, or about half of the mortality attributed to the 1920 epidemic. The 1946–1947 flu season was characterized by a previously unheard of phenomenon. The first influenza vaccine came into use in the 1940s. At this time, the vaccine contained a strain of H1N1 isolated in 1943, and this had been effective during the 1943–1944 and 1944–1945 seasons. During the 1946–1947 season, however, this once-effective vaccine totally failed to protect the military personnel who had received it. A worldwide epidemic occurred, which for a time was considered to have been a pandemic due to its vast spread, albeit a mild one, with relatively low mortality. Antigenetic analysis later revealed that the influenza A virus had undergone intrasubtypic reassortment, in which genes were swapped between two viruses of the same subtype (H1N1), resulting in an extreme drift variant but not an entirely new subtype. The new strains were so different, however, that they were for a time classified into a distinct category, though this distinction has since been lost due to more recent analysis, which supports classifying both the older and the newer strains as influenza A/H1N1. Nevertheless, this experience informed public health experts of the need to update vaccine composition periodically to account for variations in the influenza virus, even if there has been no complete shift in subtype. The 1950–1951 flu season was particularly severe in England and Wales and in Canada. Influenza A predominated. The rates of excess pneumonia and influenza mortality in these places was higher than those which would later be experienced in both the 1957 and 1968 pandemics. Liverpool in particular experienced a peak in weekly mortality even higher than that of the 1918 pandemic. Northern Europe also experienced severe epidemics this season. By contrast, the United States experienced a relatively milder epidemic. There was no observed shift in the viruses in circulation this flu season. During the 1952–1953 flu season, the Americas and Europe experienced widespread outbreaks of influenza A. Beginning the first week of January, 1953, influenza in epidemic proportions emerged in various states in the US. Outbreaks soon developed around the country, with Texas experiencing particularly high activity, though the northeast mostly saw smaller, more localized outbreaks. Schools were shuttered in many places due to the high incidence of disease among students and teachers. After an initial attempt to minimize the threat of the outbreak and a resistance to describe it as an "epidemic", the US Public Health Service eventually acknowledged it as such when deaths began to rise around the country. By the end of January, activity was decreasing around the country. Around the time that the epidemic was peaking in the US, outbreaks developed in France, Germany, and southern England and later in Scandinavia, Switzerland, and Austria; sporadic activity was reported in other parts of Europe. In the US, influenza and pneumonia mortality peaked in early February, earlier than in the three preceding flu seasons, in which mortality did not begin to rise until late February, and was the greatest out of the three preceding seasons, including 1951. It was subsequently found that strains isolated during this season were influenza A but had shifted antigenically relative to previously isolated strains, further demonstrating the significance of antigenic variation in influenza viruses. The 1967–1968 flu season was the last to be dominated by H2N2 before the emergence of H3N2 in 1968 and the consequent " Hong Kong flu " pandemic that lasted until 1970. This season was particularly severe in England and France, in which pneumonia and influenza excess mortality was two to three times greater than in other countries. By contrast, North America (the US and Canada) experienced a relatively milder epidemic than other places, with lower all-cause excess mortality and a lower increase in both pneumonia-influenza and all-cause excess mortality, both indicating that this season had a lesser impact in North America relative to other countries. In Britain, this epidemic was the "largest" it had experienced in seven years, with an estimated two million cases occurring in the population as a whole. The 2012–2013 flu season was particularly harsh in the United States , where the majority of states were reporting high rates of influenza-like illness . The Centers for Disease Control and Prevention reported that the available flu vaccine was 60% effective. It further recommended that all persons over age 6 months get the vaccine. According to one source, the season 2014-2015 saw a particularly heavy prevalence of influenza in the United Kingdom .

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Influenza_vaccine/html

Influenza vaccine

none Influenza vaccines , colloquially known as flu shots , are vaccines that protect against infection by influenza viruses . New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza . Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945. Both the World Health Organization and the U.S. Centers for Disease Control and Prevention (CDC) recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk, and the influenza vaccine is now on the WHO's List of Essential Medicines . The European Centre for Disease Prevention and Control (ECDC) also recommends yearly vaccination of high-risk groups, particularly pregnant women, the elderly, children between six months and five years, and those with certain health problems. The vaccines are generally safe, including for people who have severe egg allergies . A common side effect is soreness near the site of injection. Fever occurs in five to ten percent of children vaccinated, and temporary muscle pains or feelings of tiredness may occur. In certain years, the vaccine was linked to an increase in Guillain–Barré syndrome among older people at a rate of about one case per million doses. Influenza vaccines are not recommended in those who have had a severe allergy to previous versions of the vaccine itself. The vaccine comes in inactive and weakened viral forms. The live, weakened vaccine is generally not recommended in pregnant women, children less than two years old, adults older than 50, or people with a weakened immune system . Depending on the type it can be injected into a muscle , sprayed into the nose , or injected into the middle layer of the skin (intradermal). The intradermal vaccine was not available during the 2018–2019 and 2019–2020 influenza seasons. Vaccines are used in both humans and non-humans. Human vaccine is meant unless specifically identified as a veterinary, poultry or livestock vaccine. During the worldwide Spanish flu pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen , to developing new vaccines and serums (chiefly against what we now call Hemophilus influenzae – a name derived from the fact that it was originally considered the etiological agent – and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success." In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University . The work was extended to growth of influenza virus by several workers, including Thomas Francis , Jonas Salk , Wilson Smith, and Macfarlane Burnet , leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used during World War II . Hens' eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. In 2012, the US Food and Drug Administration (FDA) approved influenza vaccines made by growing virus in cell cultures and influenza vaccines made from recombinant proteins have been approved, with plant-based influenza vaccines being tested [ when? ] in clinical trials. The egg-based technology for producing influenza vaccine was created in the 1950s. In the US swine flu scare of 1976 , President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, a number of soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from Guillain–Barré syndrome , were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976. The 2009 H1N1 "swine flu" outbreak resulted in the rapid approval of pandemic influenza vaccines. Pandemrix was quickly modified to target the circulating strain and by late 2010, 70 million people had received a dose. Eight years later, the BMJ gained access to vaccine pharmacovigilance reports compiled by GSK (GlaxoSmithKline) during the pandemic which the BMJ reported indicated death was 5.39 fold more likely with Pandemrix vs the other pandemic vaccines. A quadrivalent flu vaccine administered by nasal mist was approved by the FDA in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012. In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of quadrivalent influenza vaccines. Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States are quadrivalent. In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States are quadrivalent. In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season. In February 2020, the FDA approved Fluad Quadrivalent for use in the United States. In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season. The B/Yamagata lineage of influenza B , one of the four lineages targeted by quadrivalent vaccines, might have become extinct in 2020/2021 due to COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. In 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, so future vaccines are recommended to be trivalent instead of quadrivalent. For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines. During the worldwide Spanish flu pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen , to developing new vaccines and serums (chiefly against what we now call Hemophilus influenzae – a name derived from the fact that it was originally considered the etiological agent – and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success." In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University . The work was extended to growth of influenza virus by several workers, including Thomas Francis , Jonas Salk , Wilson Smith, and Macfarlane Burnet , leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used during World War II . Hens' eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. In 2012, the US Food and Drug Administration (FDA) approved influenza vaccines made by growing virus in cell cultures and influenza vaccines made from recombinant proteins have been approved, with plant-based influenza vaccines being tested [ when? ] in clinical trials. The egg-based technology for producing influenza vaccine was created in the 1950s. In the US swine flu scare of 1976 , President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, a number of soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from Guillain–Barré syndrome , were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976. The 2009 H1N1 "swine flu" outbreak resulted in the rapid approval of pandemic influenza vaccines. Pandemrix was quickly modified to target the circulating strain and by late 2010, 70 million people had received a dose. Eight years later, the BMJ gained access to vaccine pharmacovigilance reports compiled by GSK (GlaxoSmithKline) during the pandemic which the BMJ reported indicated death was 5.39 fold more likely with Pandemrix vs the other pandemic vaccines. A quadrivalent flu vaccine administered by nasal mist was approved by the FDA in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012. In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of quadrivalent influenza vaccines. Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States are quadrivalent. In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States are quadrivalent. In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season. In February 2020, the FDA approved Fluad Quadrivalent for use in the United States. In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season. The B/Yamagata lineage of influenza B , one of the four lineages targeted by quadrivalent vaccines, might have become extinct in 2020/2021 due to COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. In 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, so future vaccines are recommended to be trivalent instead of quadrivalent. For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines. The US Centers for Disease Control and Prevention (CDC) recommends the flu vaccine as the best way to protect people against the flu and prevent its spread. The flu vaccine can also reduce the severity of the flu if a person contracts a strain that the vaccine did not contain. It takes about two weeks following vaccination for protective antibodies to form. A 2012 meta-analysis found that flu vaccination was effective 67 percent of the time; the populations that benefited the most were HIV-positive adults aged 18 to 55 (76 percent), healthy adults aged 18 to 46 (approximately 70 percent), and healthy children aged six months to 24 months (66 percent). The influenza vaccine also appears to protect against myocardial infarction with a benefit of 15–45%. A vaccine is assessed by its efficacy – the extent to which it reduces risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use. In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness , which is not always caused by influenza. Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift , a slight mutation in the virus that causes a new strain to arise. The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against symptomatic disease, depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza. The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly, but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization. Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines. From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%. Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older. One review found 31% effectiveness against death among adults. Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy. As of 2019 [ update ] , the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination. There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types , but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly. According to a 2016 study by faculty at the University of New South Wales, getting a flu shot was as effective or better at preventing a heart attack than even quitting smoking. In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza. In 2010, ACIP recommended annual influenza vaccination for those 6 months of age and older. Currently the CDC recommends that everyone except infants under the age of six months should receive the seasonal influenza vaccine. Vaccination campaigns usually focus special attention on people who are at high risk of serious complications if they catch the flu, such as pregnant women, children under 59 months, the elderly, and people with chronic illnesses or weakened immune systems , as well as those to whom they are exposed, such as health care workers. As the death rate is also high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant. In children, the vaccine appears to decrease the risk of influenza and possibly influenza-like illness . In children under the age of two data are limited. During the 2017–18 flu season, the CDC director indicated that 85 percent of the children who died "likely will not have been vaccinated". In the United States, as of January 2019 [ update ] , the CDC recommend that children aged six through 35 months may receive either 0.25 milliliters or 0.5 milliliters per dose of Fluzone Quadrivalent. There is no preference for one or the other dose volume of Fluzone Quadrivalent for that age group. All persons 36 months of age and older should receive 0.5 milliliters per dose of Fluzone Quadrivalent. As of October 2018 [ update ] , Afluria Quadrivalent is licensed for children six months of age and older in the United States. Children six months through 35 months of age should receive 0.25 milliliters for each dose of Afluria Quadrivalent. All persons 36 months of age and older should receive 0.5 milliliters per dose of Afluria Quadrivalent. As of February 2018 [ update ] , Afluria Tetra is licensed for adults and children five years of age and older in Canada. In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of influenza vaccination in healthy 5–18-year-olds, and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age. In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immuno-suppressed pediatric patients (46%), and in patients with inflammatory bowel disease (50%). In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do. Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%. No effect on hospitalization was found. In working adults, a review by the Cochrane Collaboration found that vaccination resulted in a modest decrease in both influenza symptoms and working days lost, without affecting transmission or influenza-related complications. In healthy working adults, influenza vaccines can provide moderate protection against virologically confirmed influenza, though such protection is greatly reduced or absent in some seasons. In health care workers, a 2006 review found a net benefit. Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths. A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered vaccine. Evidence for an effect in adults over 65 is unclear. Systematic reviews examining both randomized controlled and case–control studies found a lack of high-quality evidence. Reviews of case–control studies found effects against laboratory-confirmed influenza, pneumonia , and death among the community-dwelling elderly. The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age. In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group. There is a high-dose flu vaccine specifically formulated to provide a stronger immune response. Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine. A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States. It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant. Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older. Vaccinating health care workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population. While there is no conclusive evidence from randomized clinical trials that vaccinating health care workers helps protect elderly people from influenza, there is tentative evidence of benefit. Fluad Quad was approved for use in Australia in September 2019, Fluad Quadrivalent was approved for use in the United States in February 2020, and Fluad Tetra was approved for use in the European Union in May 2020. As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy. The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV . A vaccine is assessed by its efficacy – the extent to which it reduces risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use. In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness , which is not always caused by influenza. Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift , a slight mutation in the virus that causes a new strain to arise. The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against symptomatic disease, depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza. The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly, but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization. Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines. From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%. Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older. One review found 31% effectiveness against death among adults. Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy. As of 2019 [ update ] , the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination. There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types , but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly. According to a 2016 study by faculty at the University of New South Wales, getting a flu shot was as effective or better at preventing a heart attack than even quitting smoking. In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza. In 2010, ACIP recommended annual influenza vaccination for those 6 months of age and older. Currently the CDC recommends that everyone except infants under the age of six months should receive the seasonal influenza vaccine. Vaccination campaigns usually focus special attention on people who are at high risk of serious complications if they catch the flu, such as pregnant women, children under 59 months, the elderly, and people with chronic illnesses or weakened immune systems , as well as those to whom they are exposed, such as health care workers. As the death rate is also high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant. In children, the vaccine appears to decrease the risk of influenza and possibly influenza-like illness . In children under the age of two data are limited. During the 2017–18 flu season, the CDC director indicated that 85 percent of the children who died "likely will not have been vaccinated". In the United States, as of January 2019 [ update ] , the CDC recommend that children aged six through 35 months may receive either 0.25 milliliters or 0.5 milliliters per dose of Fluzone Quadrivalent. There is no preference for one or the other dose volume of Fluzone Quadrivalent for that age group. All persons 36 months of age and older should receive 0.5 milliliters per dose of Fluzone Quadrivalent. As of October 2018 [ update ] , Afluria Quadrivalent is licensed for children six months of age and older in the United States. Children six months through 35 months of age should receive 0.25 milliliters for each dose of Afluria Quadrivalent. All persons 36 months of age and older should receive 0.5 milliliters per dose of Afluria Quadrivalent. As of February 2018 [ update ] , Afluria Tetra is licensed for adults and children five years of age and older in Canada. In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of influenza vaccination in healthy 5–18-year-olds, and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age. In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immuno-suppressed pediatric patients (46%), and in patients with inflammatory bowel disease (50%). In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do. Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%. No effect on hospitalization was found. In working adults, a review by the Cochrane Collaboration found that vaccination resulted in a modest decrease in both influenza symptoms and working days lost, without affecting transmission or influenza-related complications. In healthy working adults, influenza vaccines can provide moderate protection against virologically confirmed influenza, though such protection is greatly reduced or absent in some seasons. In health care workers, a 2006 review found a net benefit. Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths. A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered vaccine. Evidence for an effect in adults over 65 is unclear. Systematic reviews examining both randomized controlled and case–control studies found a lack of high-quality evidence. Reviews of case–control studies found effects against laboratory-confirmed influenza, pneumonia , and death among the community-dwelling elderly. The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age. In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group. There is a high-dose flu vaccine specifically formulated to provide a stronger immune response. Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine. A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States. It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant. Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older. Vaccinating health care workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population. While there is no conclusive evidence from randomized clinical trials that vaccinating health care workers helps protect elderly people from influenza, there is tentative evidence of benefit. Fluad Quad was approved for use in Australia in September 2019, Fluad Quadrivalent was approved for use in the United States in February 2020, and Fluad Tetra was approved for use in the European Union in May 2020. As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy. The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV . Common side effects of vaccination include local injection-site reactions and cold -like symptoms. Fever, malaise , and myalgia are less common. Flu vaccines are contraindicated for people who have experienced a severe allergic reaction in response to a flu vaccine or to any component of the vaccine. LAIVs are not given to children or adolescents with severe immunodeficiency or to those who are using salicylate treatments because of the risk of developing Reye syndrome . LAIVs are also not recommended for children under the age of 2, pregnant women, and adults with immunosuppression. Inactivated flu vaccines cannot cause influenza and are regarded as safe during pregnancy. While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, and swelling around the point of injection, headache, fever, nausea or fatigue. Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting. In some people, a flu vaccine may cause serious side effects, including an allergic reaction , but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual influenza epidemic. Although Guillain–Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré. Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates). Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations, a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects. Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with egg allergies , even if severe, as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies. Studies examining the safety of influenza vaccines in people with severe egg allergies found that anaphylaxis was very rare, occurring in 1.3 cases per million doses given. Monitoring for symptoms from vaccination is recommended in those with more severe symptoms. A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine. Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available from 2012 in the US, and later in Europe and Australia. Several studies have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza AS03 -adjuvanted vaccine; efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin , serving as a trigger. Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury -based preservative. Despite some controversy in the media, the World Health Organization 's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration. Common side effects of vaccination include local injection-site reactions and cold -like symptoms. Fever, malaise , and myalgia are less common. Flu vaccines are contraindicated for people who have experienced a severe allergic reaction in response to a flu vaccine or to any component of the vaccine. LAIVs are not given to children or adolescents with severe immunodeficiency or to those who are using salicylate treatments because of the risk of developing Reye syndrome . LAIVs are also not recommended for children under the age of 2, pregnant women, and adults with immunosuppression. Inactivated flu vaccines cannot cause influenza and are regarded as safe during pregnancy. While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, and swelling around the point of injection, headache, fever, nausea or fatigue. Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting. In some people, a flu vaccine may cause serious side effects, including an allergic reaction , but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual influenza epidemic. Although Guillain–Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré. Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates). Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations, a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects. Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with egg allergies , even if severe, as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies. Studies examining the safety of influenza vaccines in people with severe egg allergies found that anaphylaxis was very rare, occurring in 1.3 cases per million doses given. Monitoring for symptoms from vaccination is recommended in those with more severe symptoms. A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine. Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available from 2012 in the US, and later in Europe and Australia. Several studies have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza AS03 -adjuvanted vaccine; efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin , serving as a trigger. Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury -based preservative. Despite some controversy in the media, the World Health Organization 's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration. Seasonal flu vaccines are available either as: [ citation needed ] a trivalent or quadrivalent intramuscular injection (IIV3, IIV4, or RIV4, that is, TIV or QIV), which contains the inactivated form of the virus a nasal spray of live attenuated influenza vaccine (LAIV, Q/LAIV), which contains the live but attenuated (weakened) form of the virus. TIV or QIV induce protection after injection (typically intramuscular, though subcutaneous and intradermal routes can also be protective) based on an immune response to the antigens present on the inactivated virus, while cold-adapted LAIV works by establishing infection in the nasal passages. Various public health organizations, including the World Health Organization (WHO), recommend that yearly influenza vaccination be routinely offered, particularly to people at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including: The flu vaccine is contraindicated for those under six months of age and those with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine. As of 2016 [ update ] , the World Health Organization (WHO) recommends seasonal influenza vaccination for: First priority: Pregnant women Second priority (in no particular order): Children aged 6–59 months Elderly Individuals with specific chronic medical conditions Health-care workers The National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada , recommends that everyone over six months of age be encouraged to receive annual influenza vaccination, and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine. Particularly: People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions People capable of transmitting influenza to those at high risk, including household contacts and health care workers People who provide essential community services Certain poultry workers Live attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season. The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority people with chronic medical conditions and health care workers. The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high herd immunity strategies for other infectious diseases such as polio and measles . This is also due in part to the financial and logistics burden associated with the need of an annual injection. In the United States routine influenza vaccination is recommended for all persons aged six months and over. It takes up to two weeks after vaccination for sufficient antibodies to develop in the body. The CDC recommends vaccination before the end of October, although it considers getting a vaccine in December or even later to be still beneficial. The U.S. military also requires a flu shot annually for its active and reserve servicemembers. According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of the nasal spray in the US) should be avoided by some groups. Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers : The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require health care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks. Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection; The CDC indicated that live attenuated influenza vaccine (LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States. Furthermore, the CDC recommends that health care personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV. The Australian Government recommends seasonal flu vaccination for everyone over the age of six months. Australia uses inactivated vaccines . Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026. The standard flu vaccine is free for the following people: children aged six months to five years; people aged 65 years and over; Aboriginal and Torres Strait Islander people aged six months and over; pregnant women; and anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity or diabetes that can lead to complications from influenza.As of 2016 [ update ] , the World Health Organization (WHO) recommends seasonal influenza vaccination for: First priority: Pregnant women Second priority (in no particular order): Children aged 6–59 months Elderly Individuals with specific chronic medical conditions Health-care workersThe National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada , recommends that everyone over six months of age be encouraged to receive annual influenza vaccination, and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine. Particularly: People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions People capable of transmitting influenza to those at high risk, including household contacts and health care workers People who provide essential community services Certain poultry workers Live attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season. The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority people with chronic medical conditions and health care workers. The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high herd immunity strategies for other infectious diseases such as polio and measles . This is also due in part to the financial and logistics burden associated with the need of an annual injection. In the United States routine influenza vaccination is recommended for all persons aged six months and over. It takes up to two weeks after vaccination for sufficient antibodies to develop in the body. The CDC recommends vaccination before the end of October, although it considers getting a vaccine in December or even later to be still beneficial. The U.S. military also requires a flu shot annually for its active and reserve servicemembers. According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of the nasal spray in the US) should be avoided by some groups. Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers : The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require health care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks. Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection; The CDC indicated that live attenuated influenza vaccine (LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States. Furthermore, the CDC recommends that health care personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV. The Australian Government recommends seasonal flu vaccination for everyone over the age of six months. Australia uses inactivated vaccines . Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026. The standard flu vaccine is free for the following people: children aged six months to five years; people aged 65 years and over; Aboriginal and Torres Strait Islander people aged six months and over; pregnant women; and anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity or diabetes that can lead to complications from influenza.Uptake of flu vaccination, both seasonally and during pandemics, is often low. Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities) and having a chronic illness. Beliefs in the safety and effectiveness of the vaccine are also important. A number of measures have been found to be useful to increase rates of vaccination in those over sixty including: patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders and encouraging physician competition. Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the H1N1/09 (later renamed A(H1N1)pdm09 [note 1] ) swine flu virus during the 2009 pandemic . However, uptake is often low. During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK, Italy, Greece, and Hong Kong. In a 2010 survey of United States health care workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. US Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%). The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits. In Victoria (Australia) public hospitals, rates of health care worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza. Uptake of flu vaccination, both seasonally and during pandemics, is often low. Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities) and having a chronic illness. Beliefs in the safety and effectiveness of the vaccine are also important. A number of measures have been found to be useful to increase rates of vaccination in those over sixty including: patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders and encouraging physician competition. Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the H1N1/09 (later renamed A(H1N1)pdm09 [note 1] ) swine flu virus during the 2009 pandemic . However, uptake is often low. During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK, Italy, Greece, and Hong Kong. In a 2010 survey of United States health care workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. US Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%). The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits. In Victoria (Australia) public hospitals, rates of health care worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza. Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses. No vaccine candidates had been announced by November 2007, but as of 2021 [ update ] , there are several universal vaccines candidates, in pre-clinical development and in clinical trials. In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly two billion courses would be required. If China pursued this goal as well, more than three billion courses would be required to serve these populations. Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population. [ citation needed ] Most flu vaccines are grown by vaccine manufacturers in fertilized chicken eggs. In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season. Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine. As of November 2007 [ update ] , both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved Optaflu , a vaccine produced by Novartis using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens. Influenza vaccines are produced in pathogen -free eggs that are eleven or twelve days old. The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release. A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius. During incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluid After the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers. Up to 3 eggs are needed to produce one dose of a trivalent vaccine, and an estimated 600 million eggs are produced each year for flu vaccine production. Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of Spodoptera frugiperda Sf9 insect cells and plant-based vaccine production (e.g., production in Nicotiana benthamiana ). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA). A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine , underwent clinical trials in 2011. On November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine. In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States. On September 17, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture). The applicant for this medicinal product is Sanofi Pasteur. Supemtek was approved for medical use in the European Union in November 2020. Australia authorised its first and cell-based vaccine in March 2021, based on an "eternal cell line" of a dog kidney . Because of the way it is produced, it produces better-matched vaccine (to the flu strains). According to the WHO , as of 2019 [ update ] , countries where influenza vaccine is produced include: Australia Brazil Canada China France Germany Hungary India Iran Japan Mexico Netherlands Nicaragua Russian Federation South Korea United Kingdom United States Vietnam In addition, Kazakhstan, Serbia and Thailand had facilities in final stages of establishing production. Most flu vaccines are grown by vaccine manufacturers in fertilized chicken eggs. In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season. Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine. As of November 2007 [ update ] , both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved Optaflu , a vaccine produced by Novartis using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens. Influenza vaccines are produced in pathogen -free eggs that are eleven or twelve days old. The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release. A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius. During incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluid After the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers. Up to 3 eggs are needed to produce one dose of a trivalent vaccine, and an estimated 600 million eggs are produced each year for flu vaccine production. Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of Spodoptera frugiperda Sf9 insect cells and plant-based vaccine production (e.g., production in Nicotiana benthamiana ). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA). A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine , underwent clinical trials in 2011. On November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine. In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States. On September 17, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture). The applicant for this medicinal product is Sanofi Pasteur. Supemtek was approved for medical use in the European Union in November 2020. Australia authorised its first and cell-based vaccine in March 2021, based on an "eternal cell line" of a dog kidney . Because of the way it is produced, it produces better-matched vaccine (to the flu strains). According to the WHO , as of 2019 [ update ] , countries where influenza vaccine is produced include: Australia Brazil Canada China France Germany Hungary India Iran Japan Mexico Netherlands Nicaragua Russian Federation South Korea United Kingdom United States Vietnam In addition, Kazakhstan, Serbia and Thailand had facilities in final stages of establishing production. The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings. In the elderly (over 65), the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination. In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations. The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden, as well as the seasonal variability in the circulating strains and the match of the vaccine. In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits. In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings. Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it. Influenza research includes molecular virology , molecular evolution , pathogenesis , host immune responses , genomics , and epidemiology . These help in developing influenza countermeasures such as vaccines , therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help researchers' understanding of what makes one strain more lethal than another, what genetic determinants most affect immunogenicity , and how the virus evolves over time. Solutions to limitations in current [ when? ] vaccine methods are being [ when? ] researched. A different approach uses Internet content to estimate the impact of an influenza vaccination campaign. More specifically, researchers have used data from Twitter and Microsoft's Bing search engine , and proposed a statistical framework which, after a series of operations, maps this information to estimates of the influenza-like illness reduction percentage in areas where vaccinations have been performed. The method has been used to quantify the impact of two flu vaccination programmes in England (2013/14 and 2014/15), where school-age children were administered a live attenuated influenza vaccine (LAIV). Notably, the impact estimates were in accordance with estimations from Public Health England based on traditional syndromic surveillance endpoints. The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based ) technology and recombinant technologies (proteins and virus-like particles). As of July 2009 [ update ] , more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month. In January 2020, the US Food and Drug Administration (FDA) approved Audenz as a vaccine for the H5N1 flu virus. Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine. A universal influenza vaccine that would not have to be designed and made for each flu season in each hemisphere would stabilize the supply, avoid error in predicting the season's variants, and protect against escape of the circulating strains by mutation. Such a vaccine has been the subject of research for decades. One approach is to use broadly neutralizing antibodies that, unlike the annual seasonal vaccines used over the first decades of the 21st century that provoke the body to generate an immune response, instead provide a component of the immune response itself. The first neutralizing antibodies were identified in 1993, via experimentation. It was found that the flu neutralizing antibodies bound to the stalk of the Hemagglutinin protein . Antibodies that could bind to the head of those proteins were identified. The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies. The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift . Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as fusion proteins , mounted on virus-like particles , on non-pathogenic viruses, as DNA, and others), are under development. Efforts have also been undertaken to develop universal vaccines that specifically activate a T-cell response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic. Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response. As of 2019, an oral flu vaccine was in clinical research . The oral vaccine candidate is based on an adenovirus type 5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant . In 2020, a Phase II human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine. An influenza vaccine and a COVID-19 vaccine may be given safely at the same time. Preliminary research indicates that influenza vaccination does not prevent COVID-19 , but may reduce the incidence and severity of COVID-19 infection. Tom Jefferson , who has led Cochrane Collaboration reviews of flu vaccines, has called clinical evidence concerning flu vaccines "rubbish" and has therefore declared them to be ineffective; he has called for placebo-controlled randomized clinical trials , which most in the field hold as unethical . His views on the efficacy of flu vaccines are rejected by medical institutions including the CDC and the National Institutes of Health , and by key figures in the field like Anthony Fauci . Michael Osterholm , who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine ... it does not protect as promoted. It's all a sales job: it's all public relations." The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based ) technology and recombinant technologies (proteins and virus-like particles). As of July 2009 [ update ] , more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month. In January 2020, the US Food and Drug Administration (FDA) approved Audenz as a vaccine for the H5N1 flu virus. Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine. A universal influenza vaccine that would not have to be designed and made for each flu season in each hemisphere would stabilize the supply, avoid error in predicting the season's variants, and protect against escape of the circulating strains by mutation. Such a vaccine has been the subject of research for decades. One approach is to use broadly neutralizing antibodies that, unlike the annual seasonal vaccines used over the first decades of the 21st century that provoke the body to generate an immune response, instead provide a component of the immune response itself. The first neutralizing antibodies were identified in 1993, via experimentation. It was found that the flu neutralizing antibodies bound to the stalk of the Hemagglutinin protein . Antibodies that could bind to the head of those proteins were identified. The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies. The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift . Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as fusion proteins , mounted on virus-like particles , on non-pathogenic viruses, as DNA, and others), are under development. Efforts have also been undertaken to develop universal vaccines that specifically activate a T-cell response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic. Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response. As of 2019, an oral flu vaccine was in clinical research . The oral vaccine candidate is based on an adenovirus type 5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant . In 2020, a Phase II human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine. An influenza vaccine and a COVID-19 vaccine may be given safely at the same time. Preliminary research indicates that influenza vaccination does not prevent COVID-19 , but may reduce the incidence and severity of COVID-19 infection. Tom Jefferson , who has led Cochrane Collaboration reviews of flu vaccines, has called clinical evidence concerning flu vaccines "rubbish" and has therefore declared them to be ineffective; he has called for placebo-controlled randomized clinical trials , which most in the field hold as unethical . His views on the efficacy of flu vaccines are rejected by medical institutions including the CDC and the National Institutes of Health , and by key figures in the field like Anthony Fauci . Michael Osterholm , who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine ... it does not protect as promoted. It's all a sales job: it's all public relations." Veterinary influenza vaccination aims to achieve the following four objectives: Protection from clinical disease Protection from infection with virulent virus Protection from virus excretion Serological differentiation of infected from vaccinated animals (so-called DIVA principle). Horses with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of two doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations." It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months. Poultry vaccines for bird flu are made inexpensively and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just hemagglutinin as in most human flu vaccines. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains – some contain an H5N2 strain isolated in Mexico years ago. 'With a chicken, if you use a vaccine that's only 85 percent related, you'll get protection,' Dr. Cardona said. 'In humans, you can get a single point mutation, and a vaccine that's 99.99 percent related won't protect you.' And they are weaker [than human vaccines]. 'Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them,' said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A( H5N1 ) vaccine contains 180. Chicken vaccines may contain less than one microgram. 'You have to be careful about extrapolating data from poultry to humans,' warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. 'Birds are more closely related to dinosaurs .'" Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of H5N1 and concluded that "at least 95 percent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90 percent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination. A filtered and purified Influenza A vaccine for humans is being developed [ when? ] and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu. Swine influenza vaccines are extensively used in pig farming in Europe and North America. Most swine flu vaccines include an H1N1 and an H3N2 strain. Swine influenza has been recognized as a major problem since the outbreak in 1976 . Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated, are made and used in the more difficult cases. The vaccine manufacturer Novartis claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent. In 2004, influenza A virus subtype H3N8 was discovered to cause canine influenza . Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004. Horses with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of two doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations." It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months. Poultry vaccines for bird flu are made inexpensively and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just hemagglutinin as in most human flu vaccines. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains – some contain an H5N2 strain isolated in Mexico years ago. 'With a chicken, if you use a vaccine that's only 85 percent related, you'll get protection,' Dr. Cardona said. 'In humans, you can get a single point mutation, and a vaccine that's 99.99 percent related won't protect you.' And they are weaker [than human vaccines]. 'Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them,' said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A( H5N1 ) vaccine contains 180. Chicken vaccines may contain less than one microgram. 'You have to be careful about extrapolating data from poultry to humans,' warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. 'Birds are more closely related to dinosaurs .'" Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of H5N1 and concluded that "at least 95 percent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90 percent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination. A filtered and purified Influenza A vaccine for humans is being developed [ when? ] and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu. Swine influenza vaccines are extensively used in pig farming in Europe and North America. Most swine flu vaccines include an H1N1 and an H3N2 strain. Swine influenza has been recognized as a major problem since the outbreak in 1976 . Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated, are made and used in the more difficult cases. The vaccine manufacturer Novartis claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent. In 2004, influenza A virus subtype H3N8 was discovered to cause canine influenza . Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004. Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance and Response System . The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012–2013 Northern Hemisphere influenza season (coincident with the approval of quadrivalent influenza vaccines), the WHO has also recommended a 2nd B-strain for use in quadrivalent vaccines. The World Health Organization (WHO) coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year. The Global Influenza Surveillance and Response System's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will predominate the next year, amounting in the end to well-informed but fallible guesswork. Formal WHO recommendations were first issued in 1973. Beginning in 1999 there have been two recommendations per year: one for the northern hemisphere and the other for the southern hemisphere. For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines.

Wiki

Pandemic influenza

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Influenza A virus

See text Influenza A virus ( IAV ) is a pathogen that causes the flu in birds and some mammals , including humans. It is an RNA virus whose subtypes have been isolated from wild birds. Occasionally, it is transmitted from wild to domestic birds, and this may cause severe disease, outbreaks, or human influenza pandemics . Each virus subtype includes a wide variety of strains with differing pathogenic profiles; some may cause disease only in one species but others to multiple ones. Because the viral genome is segmented, subtypes are neither strains nor lineages, as the subtype designation refers to proteins encoded by only two of the eight genome segments. A filtered and purified influenza A vaccine for humans has been developed and many countries have stockpiled it to allow a quick administration to the population in the event of an avian influenza pandemic . In 2011, researchers reported the discovery of an antibody effective against all types of the influenza A virus. Influenza A virus is the only species of the genus Alphainfluenzavirus of the virus family Orthomyxoviridae . There are two methods of classification, one based on surface proteins (originally serotypes ), and the other based on its behavior, mainly the host animal . There are two proteins on the surface of the viral envelope: The hemagglutinin is central to the virus's recognizing and binding to target cells, and also to its then infecting the cell with its RNA . The neuraminidase, on the other hand, is critical for the subsequent release of the daughter virus particles created within the infected cell so they can spread to other cells. [ citation needed ] Different influenza virus genomes encode different hemagglutinin and neuraminidase proteins. Based on how the different H and N proteins react to antisera , scientists defined 18 types of hemaglutinin and 11 types of neuraminidase. In modern days, determination of serotype is more commonly done by polymerase chain reaction . For example, " H5N1 " designates an influenza A subtype that has a type-5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein. Further variations exist within the subtypes and can lead to very significant differences in the virus's behavior. [lower-alpha 1] By definition, the subtyping scheme only takes into account the two outer proteins, not the at least 8 proteins internal to the virus. Variants are sometimes named according to the species (host) in which the strain is endemic or to which it is adapted. The main variants named using this convention are: [ citation needed ] Variants have also sometimes been named according to their deadliness in poultry, especially chickens: [ citation needed ] Low pathogenic avian influenza (LPAI) Highly pathogenic avian influenza (HPAI), also called deadly flu or death flu Using subtyping and host range is not sufficient to uniquely identify an influenza A virus (or a lineage of them sharing a common ancestor). To unambiguously describe a specific collection of viruses, researchers use the Influenza virus nomenclature , which describes, among other things, the serotype, time, and place of collection. Some examples include: A/Rio de Janeiro/62434/2021 (H3N2) . The starting A indicates that the virus is an influenza A virus. Rio de Janeiro indicates the place of collection. 62434 is a sequence number. 2021 indicates that the sample is collected in 2021. (H3N2) indicates the type of the virus: a H3N2 virus. A/swine/South Dakota/152B/2009 (H1N2) This example shows an additional field before the place: swine . It indicates that the sample was collected from a pig. A/California/04/2009 A(H1N1)pdm09 . This example carries an unusual designation in the last part: instead of a usual (H1N1) , it uses A(H1N1)pdm09 . This is because the CDC found it necessary to distinguish the Pandemic H1N1/09 virus lineage from older H1N1 viruses. The starting A indicates that the virus is an influenza A virus. Rio de Janeiro indicates the place of collection. 62434 is a sequence number. 2021 indicates that the sample is collected in 2021. (H3N2) indicates the type of the virus: a H3N2 virus. This example shows an additional field before the place: swine . It indicates that the sample was collected from a pig. Some variants [lower-alpha 2] are informally identified and named according to the isolate they resemble, thus are presumed to share lineage (example Fujian flu virus-like); according to their typical host (example human flu virus); according to their subtype (example H3N2); and according to their deadliness (example LP, low pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002 (H3N2) is called Fujian flu, human flu, and H3N2 flu. [ citation needed ] Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu , A/Hong Kong/1/1968 (H3N2) . The World Health Organization recommends flu shots for the 2023-2024 flu season in northern hemisphere to use the A/Darwin/9/2021 (H3N2) -like virus. There are two proteins on the surface of the viral envelope: The hemagglutinin is central to the virus's recognizing and binding to target cells, and also to its then infecting the cell with its RNA . The neuraminidase, on the other hand, is critical for the subsequent release of the daughter virus particles created within the infected cell so they can spread to other cells. [ citation needed ] Different influenza virus genomes encode different hemagglutinin and neuraminidase proteins. Based on how the different H and N proteins react to antisera , scientists defined 18 types of hemaglutinin and 11 types of neuraminidase. In modern days, determination of serotype is more commonly done by polymerase chain reaction . For example, " H5N1 " designates an influenza A subtype that has a type-5 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein. Further variations exist within the subtypes and can lead to very significant differences in the virus's behavior. [lower-alpha 1] By definition, the subtyping scheme only takes into account the two outer proteins, not the at least 8 proteins internal to the virus. Variants are sometimes named according to the species (host) in which the strain is endemic or to which it is adapted. The main variants named using this convention are: [ citation needed ] Variants have also sometimes been named according to their deadliness in poultry, especially chickens: [ citation needed ] Low pathogenic avian influenza (LPAI) Highly pathogenic avian influenza (HPAI), also called deadly flu or death fluUsing subtyping and host range is not sufficient to uniquely identify an influenza A virus (or a lineage of them sharing a common ancestor). To unambiguously describe a specific collection of viruses, researchers use the Influenza virus nomenclature , which describes, among other things, the serotype, time, and place of collection. Some examples include: A/Rio de Janeiro/62434/2021 (H3N2) . The starting A indicates that the virus is an influenza A virus. Rio de Janeiro indicates the place of collection. 62434 is a sequence number. 2021 indicates that the sample is collected in 2021. (H3N2) indicates the type of the virus: a H3N2 virus. A/swine/South Dakota/152B/2009 (H1N2) This example shows an additional field before the place: swine . It indicates that the sample was collected from a pig. A/California/04/2009 A(H1N1)pdm09 . This example carries an unusual designation in the last part: instead of a usual (H1N1) , it uses A(H1N1)pdm09 . This is because the CDC found it necessary to distinguish the Pandemic H1N1/09 virus lineage from older H1N1 viruses. The starting A indicates that the virus is an influenza A virus. Rio de Janeiro indicates the place of collection. 62434 is a sequence number. 2021 indicates that the sample is collected in 2021. (H3N2) indicates the type of the virus: a H3N2 virus. This example shows an additional field before the place: swine . It indicates that the sample was collected from a pig. Some variants [lower-alpha 2] are informally identified and named according to the isolate they resemble, thus are presumed to share lineage (example Fujian flu virus-like); according to their typical host (example human flu virus); according to their subtype (example H3N2); and according to their deadliness (example LP, low pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002 (H3N2) is called Fujian flu, human flu, and H3N2 flu. [ citation needed ] Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu , A/Hong Kong/1/1968 (H3N2) . The World Health Organization recommends flu shots for the 2023-2024 flu season in northern hemisphere to use the A/Darwin/9/2021 (H3N2) -like virus. The annual flu (also called "seasonal flu" or "human flu") in the US "results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S." Globally the toll of influenza virus is estimated at 290,000–645,000 deaths annually, exceeding previous estimates. The annually updated, trivalent influenza vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2 , H1N1 , and B influenza viruses. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. [ citation needed ] "Contemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host." FI6 , an antibody that targets the hemagglutinin protein, was discovered in 2011. FI6 is the only known antibody effective against all 16 subtypes of the influenza A virus. FI6 , an antibody that targets the hemagglutinin protein, was discovered in 2011. FI6 is the only known antibody effective against all 16 subtypes of the influenza A virus. Influenza A viruses are negative-sense , single-stranded, segmented RNA virus . The several subtypes are labeled according to an H number (for the type of hemagglutinin ) and an N number (for the type of neuraminidase ). There are 18 different known H antigens (H1 to H18) and 11 different known N antigens (N1 to N11). H17N10 was isolated from fruit bats in 2012. H18N11 was discovered in a Peruvian bat in 2013. Influenza type A viruses are very similar in structure to influenza viruses types B, C, and D. The virus particle (also called the virion) is 80–120 nanometers in diameter such that the smallest virions adopt an elliptical shape. The length of each particle varies considerably, owing to the fact that influenza is pleomorphic, and can be in excess of many tens of micrometers, producing filamentous virions. Confusion about the nature of influenza virus pleomorphy stems from the observation that lab adapted strains typically lose the ability to form filaments and that these lab adapted strains were the first to be visualized by electron microscopy. Despite these varied shapes, the virions of all influenza type A viruses are similar in composition. They are all made up of a viral envelope containing two main types of proteins, wrapped around a central core. The two large proteins found on the outside of viral particles are hemagglutinin (HA) and neuraminidase (NA). HA is a protein that mediates binding of the virion to target cells and entry of the viral genome into the target cell. NA is involved in release from the abundant non-productive attachment sites present in mucus as well as the release of progeny virions from infected cells. These proteins are usually the targets for antiviral drugs. Furthermore, they are also the antigen proteins to which a host's antibodies can bind and trigger an immune response. Influenza type A viruses are categorized into subtypes based on the type of these two proteins on the surface of the viral envelope. There are 16 subtypes of HA and 9 subtypes of NA known, but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans. The central core of a virion contains the viral genome and other viral proteins that package and protect the genetic material. Unlike the genomes of most organisms (including humans, animals, plants, and bacteria) which are made up of double-stranded DNA, many viral genomes are made up of a different, single-stranded nucleic acid called RNA. Unusually for a virus, though, the influenza type A virus genome is not a single piece of RNA; instead, it consists of segmented pieces of negative-sense RNA, each piece containing either one or two genes which code for a gene product (protein). The term negative-sense RNA just implies that the RNA genome cannot be translated into protein directly; it must first be transcribed to positive-sense RNA before it can be translated into protein products. The segmented nature of the genome allows for the exchange of entire genes between different viral strains. The entire Influenza A virus genome is 13,588 bases long and is contained on eight RNA segments that code for at least 10 but up to 14 proteins, depending on the strain. The relevance or presence of alternate gene products can vary: Segment 1 encodes RNA polymerase subunit (PB2). Segment 2 encodes RNA polymerase subunit (PB1) and the PB1-F2 protein, which induces cell death, by using different reading frames from the same RNA segment. Segment 3 encodes RNA polymerase subunit (PA) and the PA-X protein, which has a role in host transcription shutoff. Segment 4 encodes for HA (hemagglutinin). About 500 molecules of hemagglutinin are needed to make one virion. HA determines the extent and severity of a viral infection in a host organism. Segment 5 encodes NP, which is a nucleoprotein. Segment 6 encodes NA (neuraminidase). About 100 molecules of neuraminidase are needed to make one virion. Segment 7 encodes two matrix proteins (M1 and M2) by using different reading frames from the same RNA segment. About 3,000 matrix protein molecules are needed to make one virion. Segment 8 encodes two distinct non-structural proteins (NS1 and NEP) by using different reading frames from the same RNA segment. The RNA segments of the viral genome have complementary base sequences at the terminal ends, allowing them to bond to each other with hydrogen bonds. Transcription of the viral (-) sense genome (vRNA) can only proceed after the PB2 protein binds to host capped RNAs, allowing for the PA subunit to cleave several nucleotides after the cap. This host-derived cap and accompanied nucleotides serve as the primer for viral transcription initiation. Transcription proceeds along the vRNA until a stretch of several uracil bases is reached, initiating a 'stuttering' whereby the nascent viral mRNA is poly-adenylated, producing a mature transcript for nuclear export and translation by host machinery. The RNA synthesis takes place in the cell nucleus, while the synthesis of proteins takes place in the cytoplasm. Once the viral proteins are assembled into virions, the assembled virions leave the nucleus and migrate towards the cell membrane. The host cell membrane has patches of viral transmembrane proteins (HA, NA, and M2) and an underlying layer of the M1 protein which assist the assembled virions to budding through the membrane, releasing finished enveloped viruses into the extracellular fluid. The subtypes of influenza A virus are estimated to have diverged 2,000 years ago. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. Influenza virus is able to undergo multiplicity reactivation after inactivation by UV radiation, or by ionizing radiation. If any of the eight RNA strands that make up the genome contains damage that prevents replication or expression of an essential gene, the virus is not viable when it alone infects a cell (a single infection). However, when two or more damaged viruses infect the same cell (multiple infection), viable progeny viruses can be produced provided each of the eight genomic segments is present in at least one undamaged copy. That is, multiplicity reactivation can occur. [ citation needed ] Upon infection, influenza virus induces a host response involving increased production of reactive oxygen species, and this can damage the virus genome. If, under natural conditions, virus survival is ordinarily vulnerable to the challenge of oxidative damage, then multiplicity reactivation is likely selectively advantageous as a kind of genomic repair process. It has been suggested that multiplicity reactivation involving segmented RNA genomes may be similar to the earliest evolved form of sexual interaction in the RNA world that likely preceded the DNA world. "Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1, H1N2, and H3N2 are the only known influenza A virus subtypes currently circulating among humans. Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include: Human flu symptoms usually include fever, cough, sore throat , muscle aches , conjunctivitis and, in severe cases, breathing problems and pneumonia that may be fatal. The severity of the infection will depend in large part on the state of the infected person's immune system and if the victim has been exposed to the strain before, and is therefore partially immune. Follow-up studies on the impact of statins on influenza virus replication show that pre-treatment of cells with atorvastatin suppresses virus growth in culture. Highly pathogenic H5N1 avian influenza in a human is far worse, killing 50% of humans who catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. The influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are: H10N3 In May 2021, in Zhenjiang , China H10N3 was reported for the first time in humans. One person was infected. According to Jeffery Taubenberger : All influenza A pandemics since [the Spanish flu pandemic], and indeed almost all cases of influenza A worldwide (excepting human infections from avian viruses such as H5N1 and H7N7), have been caused by descendants of the 1918 virus, including "drifted" H1N1 viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the 1918 virus, updated by subsequently incorporated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the "mother" of all pandemics. Researchers from the National Institutes of Health used data from the Influenza Genome Sequencing Project and concluded that during the ten-year period examined, most of the time the hemagglutinin gene in H3N2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. This resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid evolution , rapidly sweeping through the population and eliminating most other variants. In the short-term evolution of influenza A virus, a 2006 study found that stochastic, or random, processes are key factors. Influenza A virus HA antigenic evolution appears to be characterized more by punctuated, sporadic jumps as opposed to a constant rate of antigenic change. Using phylogenetic analysis of 413 complete genomes of human influenza A viruses that were collected throughout the state of New York, the authors of Nelson et al. 2006 were able to show that genetic diversity, and not antigenic drift, shaped the short-term evolution of influenza A via random migration and reassortment. The evolution of these viruses is dominated more by the random importation of genetically different viral strains from other geographic locations and less by natural selection. Within a given season, adaptive evolution is infrequent and had an overall weak effect as evidenced from the data gathered from the 413 genomes. Phylogenetic analysis revealed the different strains were derived from newly imported genetic material as opposed to isolates that had been circulating in New York in previous seasons. Therefore, the gene flow in and out of this population, and not natural selection, was more important in the short term. [ citation needed ]According to Jeffery Taubenberger : All influenza A pandemics since [the Spanish flu pandemic], and indeed almost all cases of influenza A worldwide (excepting human infections from avian viruses such as H5N1 and H7N7), have been caused by descendants of the 1918 virus, including "drifted" H1N1 viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the 1918 virus, updated by subsequently incorporated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the "mother" of all pandemics. Researchers from the National Institutes of Health used data from the Influenza Genome Sequencing Project and concluded that during the ten-year period examined, most of the time the hemagglutinin gene in H3N2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. This resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid evolution , rapidly sweeping through the population and eliminating most other variants. In the short-term evolution of influenza A virus, a 2006 study found that stochastic, or random, processes are key factors. Influenza A virus HA antigenic evolution appears to be characterized more by punctuated, sporadic jumps as opposed to a constant rate of antigenic change. Using phylogenetic analysis of 413 complete genomes of human influenza A viruses that were collected throughout the state of New York, the authors of Nelson et al. 2006 were able to show that genetic diversity, and not antigenic drift, shaped the short-term evolution of influenza A via random migration and reassortment. The evolution of these viruses is dominated more by the random importation of genetically different viral strains from other geographic locations and less by natural selection. Within a given season, adaptive evolution is infrequent and had an overall weak effect as evidenced from the data gathered from the 413 genomes. Phylogenetic analysis revealed the different strains were derived from newly imported genetic material as opposed to isolates that had been circulating in New York in previous seasons. Therefore, the gene flow in and out of this population, and not natural selection, was more important in the short term. [ citation needed ]Fowl act as natural asymptomatic carriers of influenza A viruses. Prior to the current [ when? ] H5N1 epizootic, strains of influenza A virus had been demonstrated to be transmitted from wildfowl to only birds, pigs, horses, seals , whales and humans; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse. Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally, viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. H5N1 has been shown to be transmitted to tigers, leopards, and domestic cats that were fed uncooked domestic fowl (chickens) with the virus. H3N8 viruses from horses have crossed over and caused outbreaks in dogs. Laboratory mice have been infected successfully with a variety of avian flu genotypes. Influenza A viruses spread in the air and in manure , and survives longer in cold weather. They can also be transmitted by contaminated feed, water, equipment, and clothing; however, there is no evidence the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent strains can cause death within a few days. Avian influenza viruses that the World Organisation for Animal Health and others test for to control poultry disease include H5N1 , H7N2 , H1N7 , H7N3 , H13N6 , H5N9 , H11N6, H3N8 , H9N2 , H5N2 , H4N8, H10N7 , H2N2 , H8N4, H14N5, H6N5, and H12N5. [ citation needed ] *Outbreaks with significant spread to numerous farms, resulting in great economic losses. Most other outbreaks involved little or no spread from the initially infected farms. More than 400 harbor seal deaths were recorded in New England between December 1979 and October 1980, from acute pneumonia caused by the influenza virus, A/Seal/Mass/1/180 (H7N7). Swine influenza (or "pig influenza") refers to a subset of Orthomyxoviridae that create influenza and are endemic in pigs. The species of Orthomyxoviridae that can cause flu in pigs are influenza A virus and influenza C virus , but not all genotypes of these two species infect pigs. The known subtypes of influenza A virus that create influenza and are endemic in pigs are H1N1, H1N2, H3N1 and H3N2. In 1997, H3N2 viruses from humans entered the pig population, causing widespread disease among pigs. Horse flu (or "equine influenza") refers to varieties of influenza A virus that affect horses. Horse flu viruses were only isolated in 1956. The two main types of virus are called equine-1 (H7N7), which commonly affects horse heart muscle, and equine-2 (H3N8), which is usually more severe. H3N8 viruses from horses have infected dogs. Dog flu (or "canine influenza") refers to varieties of influenza A virus that affect dogs. The equine influenza virus H3N8 was found to infect and kill – with respiratory illness – greyhound race dogs at a Florida racetrack in January 2004. Bat flu (or "Bat influenza") refers to the H17N10 and H18N11 influenza A virus strains that were discovered in Central and South American fruit bats as well as a H9N2 virus isolated from the Egyptian fruit bat. Until now it is unclear whether these bat-derived viruses are circulating in any non-bat species and whether they pose a zoonotic threat. Initial characterization of the H18N11 subtype, however, suggests that this bat influenza virus is not well adapted to any other species than bats. H3N8 is now endemic in birds, horses and dogs.Fowl act as natural asymptomatic carriers of influenza A viruses. Prior to the current [ when? ] H5N1 epizootic, strains of influenza A virus had been demonstrated to be transmitted from wildfowl to only birds, pigs, horses, seals , whales and humans; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse. Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally, viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics. H5N1 has been shown to be transmitted to tigers, leopards, and domestic cats that were fed uncooked domestic fowl (chickens) with the virus. H3N8 viruses from horses have crossed over and caused outbreaks in dogs. Laboratory mice have been infected successfully with a variety of avian flu genotypes. Influenza A viruses spread in the air and in manure , and survives longer in cold weather. They can also be transmitted by contaminated feed, water, equipment, and clothing; however, there is no evidence the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent strains can cause death within a few days. Avian influenza viruses that the World Organisation for Animal Health and others test for to control poultry disease include H5N1 , H7N2 , H1N7 , H7N3 , H13N6 , H5N9 , H11N6, H3N8 , H9N2 , H5N2 , H4N8, H10N7 , H2N2 , H8N4, H14N5, H6N5, and H12N5. [ citation needed ] *Outbreaks with significant spread to numerous farms, resulting in great economic losses. Most other outbreaks involved little or no spread from the initially infected farms. More than 400 harbor seal deaths were recorded in New England between December 1979 and October 1980, from acute pneumonia caused by the influenza virus, A/Seal/Mass/1/180 (H7N7). Swine influenza (or "pig influenza") refers to a subset of Orthomyxoviridae that create influenza and are endemic in pigs. The species of Orthomyxoviridae that can cause flu in pigs are influenza A virus and influenza C virus , but not all genotypes of these two species infect pigs. The known subtypes of influenza A virus that create influenza and are endemic in pigs are H1N1, H1N2, H3N1 and H3N2. In 1997, H3N2 viruses from humans entered the pig population, causing widespread disease among pigs. Horse flu (or "equine influenza") refers to varieties of influenza A virus that affect horses. Horse flu viruses were only isolated in 1956. The two main types of virus are called equine-1 (H7N7), which commonly affects horse heart muscle, and equine-2 (H3N8), which is usually more severe. H3N8 viruses from horses have infected dogs. Dog flu (or "canine influenza") refers to varieties of influenza A virus that affect dogs. The equine influenza virus H3N8 was found to infect and kill – with respiratory illness – greyhound race dogs at a Florida racetrack in January 2004.Bat flu (or "Bat influenza") refers to the H17N10 and H18N11 influenza A virus strains that were discovered in Central and South American fruit bats as well as a H9N2 virus isolated from the Egyptian fruit bat. Until now it is unclear whether these bat-derived viruses are circulating in any non-bat species and whether they pose a zoonotic threat. Initial characterization of the H18N11 subtype, however, suggests that this bat influenza virus is not well adapted to any other species than bats. H3N8 is now endemic in birds, horses and dogs.Influenza A virus has the following subtypes: [ citation needed ]

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Pandemic influenza

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Influenza A virus subtype H1N1

In virology , influenza A virus subtype H1N1 ( A/H1N1 ) is a subtype of influenza A virus . Major outbreaks of H1N1 strains in humans include the 1918 Spanish flu pandemic , the 1977 Russian flu pandemic and the 2009 swine flu pandemic . It is an orthomyxovirus that contains the glycoproteins hemagglutinin (H) and neuraminidase (N), antigens whose subtypes are used to classify the strains of the virus as H1N1, H1N2 etc. Hemagglutinin causes red blood cells to clump together and binds the virus to the infected cell. Neuraminidase is a type of glycoside hydrolase enzyme which helps to move the virus particles through the infected cell and assist in budding from the host cells. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza , for instance in 2004–2005. Other strains of H1N1 are endemic in pigs ( swine influenza ) and in birds ( avian influenza ). Its size is 80 to 120 nm (3.1 × 10 −6 to 4.7 × 10 −6 in) in diameter. Genetic analyses of virus from tissue preserved medically or in permafrost suggest that modern seasonal H1N1 strains descended from the 1918 flu pandemic virus, but not conclusively so. Swine influenza (also known as swine flu or pig flu) is a respiratory disease that occurs in pigs that is caused by the Influenza A virus. Influenza viruses that are normally found in swine are known as swine influenza viruses (SIVs). The known SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2 , H3N1 , H3N2 and H2N3 . Pigs can also become infected with the H4N6 and H9N2 subtypes. Swine influenza virus is common throughout pig populations worldwide. Transmission of the virus from pigs to humans is not common and does not always lead to human influenza, often resulting only in the production of antibodies in the blood. If transmission does cause human influenza, it is called zoonotic swine flu or a variant virus. People with regular exposure to pigs are at increased risk of swine flu infection. Properly cooking the meat of an infected animal removes the risk of infection. Pigs experimentally infected with the strain of swine flu that caused the human pandemic of 2009–10 showed clinical signs of flu within four days, and the virus spread to other uninfected pigs housed with the infected ones. The 1918 flu was an unusually severe and deadly strain of H1N1 avian influenza , which killed from 17 to 50 or more million people worldwide over about a year in 1918 and 1920. It was one of the deadliest pandemics in human history . The 1918 flu caused an abnormally high number of deaths, possibly due to it provoking a cytokine storm in the body. (The H5N1 bird flu , also an Influenza A virus, has a similar effect.) After the 1918 flu infected lung cells, it frequently led to overstimulation of the immune system via release of immune response-stimulating cytokines (proteins that transmit signals between cells) into the lung tissue. This leads to extensive leukocyte migration towards the lungs, resulting in the destruction of lung cells and secretion of blood and mucus into the alveoli and airways. This makes it difficult for the patient to breathe and can result in suffocation. In contrast to other pandemics, which mostly kill the old and the very young, the 1918 pandemic killed unusual numbers of young adults, which may have been due to their healthy immune systems mounting a too-strong and damaging response to the infection. The term "Spanish" flu was coined because Spain was at the time the only European country where the press were printing reports of the outbreak, which had killed thousands in the armies fighting World War I (1914–1918). Other countries suppressed the news in order to protect morale. In 1976, a novel swine influenza A (H1N1) caused severe respiratory illness in 13 soldiers, with one death at Fort Dix , New Jersey. The virus was detected only from 19 January to 9 February and did not spread beyond Fort Dix. Retrospective serologic testing subsequently demonstrated that up to 230 soldiers had been infected with the novel virus, which was an H1N1 strain. The cause of the outbreak is still unknown and no exposure to pigs was identified. The 1977 Russian flu pandemic was caused by strain Influenza A/USSR/90/77 (H1N1) . It infected mostly children and young adults under 23; because a similar strain was prevalent in 1947–57, most adults had substantial immunity. Later analysis found that the re-emergent strain had been circulating for approximately one year before it was detected in China and Russia. The virus was included in the 1978–79 influenza vaccine . In the 2009 flu pandemic , the virus isolated from patients in the United States was found to be made up of genetic elements from four different flu viruses – North American swine influenza, North American avian influenza, human influenza, and swine influenza virus typically found in Asia and Europe – "an unusually mongrelised mix of genetic sequences." This new strain appears to be a result of reassortment of human influenza and swine influenza viruses, in all four different strains of subtype H1N1. Preliminary genetic characterization found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in U.S. pigs since 1999, but the neuraminidase (NA) and matrix protein (M) genes resembled versions present in European swine flu isolates. The six genes from American swine flu are themselves mixtures of swine flu, bird flu, and human flu viruses. While viruses with this genetic makeup had not previously been found to be circulating in humans or pigs, there is no formal national surveillance system to determine what viruses are circulating in pigs in the U.S. In April 2009, an outbreak of influenza-like illness (ILI) occurred in Mexico and then in the United States; the CDC reported seven cases of novel A/H1N1 influenza and promptly shared the genetic sequences on the GISAID database. With similar timely sharing of data for Mexican isolates, by 24 April it became clear that the outbreak of ILI in Mexico and the confirmed cases of novel influenza A in the southwest US were related and WHO issued a health advisory on the outbreak of "influenza-like illness in the United States and Mexico". The disease then spread very rapidly, with the number of confirmed cases rising to 2,099 by 7 May, despite aggressive measures taken by the Mexican government to curb the spread of the disease. The outbreak had been predicted a year earlier by noticing the increasing number of replikins , a type of peptide , found in the virus. On 11 June 2009, the WHO declared an H1N1 pandemic, moving the alert level to phase 6, marking the first global pandemic since the 1968 Hong Kong flu . On 25 October 2009, U.S. President Barack Obama officially declared H1N1 a national emergency . The President's declaration caused many U.S. employers to take actions to help stem the spread of the swine flu and to accommodate employees and / or workflow which may have been impacted by an outbreak. A study conducted in coordination with the University of Michigan Health Service – scheduled for publication in the December 2009 American Journal of Roentgenology – warned that H1N1 flu can cause pulmonary embolism , surmised as a leading cause of death in this pandemic. The study authors suggest physician evaluation via contrast enhanced CT scans for the presence of pulmonary emboli when caring for patients diagnosed with respiratory complications from a "severe" case of the H1N1 flu. H1N1 may induce other embolic events, such as myocardial infarction , bilateral massive DVT , arterial thrombus of infrarenal aorta, thrombosis of right external iliac vein and common femoral vein or cerebral gas embolism. The type of embolic events caused by H1N1 infection are summarized in a 2010 review by Dimitroulis Ioannis et al. The 21 March 2010 worldwide update, by the U.N.'s World Health Organization (WHO), states that "213 countries and overseas territories/communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16,931 deaths." As of 30 May 2010 [ update ] , worldwide update by World Health Organization (WHO) more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18,138 deaths. The research team of Andrew Miller showed pregnant patients are at increased risk. It has been suggested that pregnant women and certain populations such as native North Americans have a greater likelihood of developing a T helper type 2 response to H1N1 influenza which may be responsible for the systemic inflammatory response syndrome that causes pulmonary edema and death. On 26 April 2011, an H1N1 pandemic preparedness alert was issued by the World Health Organization for the Americas. In August 2011, according to the U.S. Geological Survey and the CDC, northern sea otters off the coast of Washington state were infected with the same version of the H1N1 flu virus that caused the 2009 pandemic and "may be a newly identified animal host of influenza viruses". In May 2013, seventeen people died during an H1N1 outbreak in Venezuela , and a further 250 were infected. As of early January 2014, Texas health officials have confirmed at least thirty-three H1N1 deaths and widespread outbreak during the 2013/2014 flu season, while twenty-one more deaths have been reported across the US. Nine people have been reported dead from an outbreak in several Canadian cities, and Mexico reports outbreaks resulting in at least one death. Spanish health authorities have confirmed 35 H1N1 cases in the Aragon region, 18 of whom are in intensive care. On 17 March 2014, three cases were confirmed with a possible fourth awaiting results occurring at the Centre for Addiction and Mental Health in Toronto , Ontario, Canada. With more than 300 infections and over 20 deaths, India's health ministry declared an outbreak "well under control" with "no reason to panic" in April 2012. According to the Indian Health Ministry , 31,974 cases of swine flu had been reported and 1,895 people had died from an outbreak by mid-March. Maldives reported swine flu in early 2017; [ better source needed ] 501 people were tested for the disease and 185 (37%) of those tested were positive for the disease. Four of those who tested positive from these 185 died due to this disease. The total number of people who have died due to the disease is unknown. Patient Zero was never identified. Schools were closed for a week due to the disease, but were ordered by the Ministry of Education to open after the holidays even though the disease was not fully under control. Myanmar reported H1N1 in late July 2017. As of 27 July, there were 30 confirmed cases and six people had died. The Ministry of Health and Sports of Myanmar sent an official request to WHO to provide help to control the virus; and also mentioned that the government would be seeking international assistance, including from the UN , China and the United States. Pakistan reported H1N1 cases mostly arising from the city of Multan , with deaths resulting from the epidemic reaching 42. There have also been confirmed cases in cities of Gujranwala and Lahore . An outbreak of swine flu in the European Union member state was reported in mid-January 2019, with the island's main state hospital overcrowded within a week, with more than 30 cases being treated. In January 2019 an outbreak of H1N1 was recorded in Morocco, with nine confirmed fatalities. In November 2019 an outbreak of H1N1 was recorded in Iran, with 56 fatalities and 4,000 people hospitalized. The G4 virus , also known as the "G4 swine flu virus" (G4) and "G4 EA H1N1", is a swine influenza virus strain discovered in China. The virus is a variant genotype 4 (G4) Eurasian avian-like (EA) H1N1 virus that mainly affects pigs, but there is some evidence of it infecting people. A 2020 peer-reviewed paper from the Proceedings of the National Academy of Sciences ( PNAS ) stated that "G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans ... Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring of swine working populations should be promptly implemented." Michael Ryan, executive director of the World Health Organization (WHO) Health Emergencies Program , stated in July 2020 that this strain of influenza virus was not new and had been under surveillance since 2011. The Chinese CDC said it had implemented an influenza surveillance program in 2010, analyzing more than 400,000 tests annually, to facilitate early identification of influenza. Of those, 13 A(H1N1) cases were detected, of which three were of the G4 variant. The study stated that almost 30,000 swine had been monitored via nasal swabs between 2011 and 2018. While other variants of the virus have appeared and diminished, the study claimed the G4 variant had sharply increased since 2016 to become the predominant strain. The Chinese Ministry of Agriculture and Rural Affairs rebutted the study, saying that the number of pigs sampled was too small to demonstrate G4 had become the dominant strain and that the media had interpreted the study "in an exaggerated and nonfactual way". They also said the infected workers "did not show flu symptoms and the test sample is not representative of the pig population in China". The US Centers for Disease Control and Prevention (CDC) said the study suggested that human infection by the G4 virus is more common than it was thought to be. Both the European Centre for Disease Prevention and Control (ECDC) and the US CDC stated that, like all flu viruses with pandemic potential, the variant is a concern that will be monitored. The ECDC stated that "the most important intervention in preparing for the pandemic potential of influenza viruses is the development and use of human vaccines ...". Health officials (including Anthony Fauci ) have said that the virus should be monitored, particularly among those in close contact with pigs, but it is not an immediate threat. While there have been no reported cases or evidence of the virus outside China as of July 2020, Smithsonian Magazine reported in July 2020 that scientists agree that the virus should be closely monitored , but because it "so far cannot jump from person to person", it should not be a cause for alarm yet. The 1918 flu was an unusually severe and deadly strain of H1N1 avian influenza , which killed from 17 to 50 or more million people worldwide over about a year in 1918 and 1920. It was one of the deadliest pandemics in human history . The 1918 flu caused an abnormally high number of deaths, possibly due to it provoking a cytokine storm in the body. (The H5N1 bird flu , also an Influenza A virus, has a similar effect.) After the 1918 flu infected lung cells, it frequently led to overstimulation of the immune system via release of immune response-stimulating cytokines (proteins that transmit signals between cells) into the lung tissue. This leads to extensive leukocyte migration towards the lungs, resulting in the destruction of lung cells and secretion of blood and mucus into the alveoli and airways. This makes it difficult for the patient to breathe and can result in suffocation. In contrast to other pandemics, which mostly kill the old and the very young, the 1918 pandemic killed unusual numbers of young adults, which may have been due to their healthy immune systems mounting a too-strong and damaging response to the infection. The term "Spanish" flu was coined because Spain was at the time the only European country where the press were printing reports of the outbreak, which had killed thousands in the armies fighting World War I (1914–1918). Other countries suppressed the news in order to protect morale. In 1976, a novel swine influenza A (H1N1) caused severe respiratory illness in 13 soldiers, with one death at Fort Dix , New Jersey. The virus was detected only from 19 January to 9 February and did not spread beyond Fort Dix. Retrospective serologic testing subsequently demonstrated that up to 230 soldiers had been infected with the novel virus, which was an H1N1 strain. The cause of the outbreak is still unknown and no exposure to pigs was identified. The 1977 Russian flu pandemic was caused by strain Influenza A/USSR/90/77 (H1N1) . It infected mostly children and young adults under 23; because a similar strain was prevalent in 1947–57, most adults had substantial immunity. Later analysis found that the re-emergent strain had been circulating for approximately one year before it was detected in China and Russia. The virus was included in the 1978–79 influenza vaccine . In the 2009 flu pandemic , the virus isolated from patients in the United States was found to be made up of genetic elements from four different flu viruses – North American swine influenza, North American avian influenza, human influenza, and swine influenza virus typically found in Asia and Europe – "an unusually mongrelised mix of genetic sequences." This new strain appears to be a result of reassortment of human influenza and swine influenza viruses, in all four different strains of subtype H1N1. Preliminary genetic characterization found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in U.S. pigs since 1999, but the neuraminidase (NA) and matrix protein (M) genes resembled versions present in European swine flu isolates. The six genes from American swine flu are themselves mixtures of swine flu, bird flu, and human flu viruses. While viruses with this genetic makeup had not previously been found to be circulating in humans or pigs, there is no formal national surveillance system to determine what viruses are circulating in pigs in the U.S. In April 2009, an outbreak of influenza-like illness (ILI) occurred in Mexico and then in the United States; the CDC reported seven cases of novel A/H1N1 influenza and promptly shared the genetic sequences on the GISAID database. With similar timely sharing of data for Mexican isolates, by 24 April it became clear that the outbreak of ILI in Mexico and the confirmed cases of novel influenza A in the southwest US were related and WHO issued a health advisory on the outbreak of "influenza-like illness in the United States and Mexico". The disease then spread very rapidly, with the number of confirmed cases rising to 2,099 by 7 May, despite aggressive measures taken by the Mexican government to curb the spread of the disease. The outbreak had been predicted a year earlier by noticing the increasing number of replikins , a type of peptide , found in the virus. On 11 June 2009, the WHO declared an H1N1 pandemic, moving the alert level to phase 6, marking the first global pandemic since the 1968 Hong Kong flu . On 25 October 2009, U.S. President Barack Obama officially declared H1N1 a national emergency . The President's declaration caused many U.S. employers to take actions to help stem the spread of the swine flu and to accommodate employees and / or workflow which may have been impacted by an outbreak. A study conducted in coordination with the University of Michigan Health Service – scheduled for publication in the December 2009 American Journal of Roentgenology – warned that H1N1 flu can cause pulmonary embolism , surmised as a leading cause of death in this pandemic. The study authors suggest physician evaluation via contrast enhanced CT scans for the presence of pulmonary emboli when caring for patients diagnosed with respiratory complications from a "severe" case of the H1N1 flu. H1N1 may induce other embolic events, such as myocardial infarction , bilateral massive DVT , arterial thrombus of infrarenal aorta, thrombosis of right external iliac vein and common femoral vein or cerebral gas embolism. The type of embolic events caused by H1N1 infection are summarized in a 2010 review by Dimitroulis Ioannis et al. The 21 March 2010 worldwide update, by the U.N.'s World Health Organization (WHO), states that "213 countries and overseas territories/communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16,931 deaths." As of 30 May 2010 [ update ] , worldwide update by World Health Organization (WHO) more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18,138 deaths. The research team of Andrew Miller showed pregnant patients are at increased risk. It has been suggested that pregnant women and certain populations such as native North Americans have a greater likelihood of developing a T helper type 2 response to H1N1 influenza which may be responsible for the systemic inflammatory response syndrome that causes pulmonary edema and death. On 26 April 2011, an H1N1 pandemic preparedness alert was issued by the World Health Organization for the Americas. In August 2011, according to the U.S. Geological Survey and the CDC, northern sea otters off the coast of Washington state were infected with the same version of the H1N1 flu virus that caused the 2009 pandemic and "may be a newly identified animal host of influenza viruses". In May 2013, seventeen people died during an H1N1 outbreak in Venezuela , and a further 250 were infected. As of early January 2014, Texas health officials have confirmed at least thirty-three H1N1 deaths and widespread outbreak during the 2013/2014 flu season, while twenty-one more deaths have been reported across the US. Nine people have been reported dead from an outbreak in several Canadian cities, and Mexico reports outbreaks resulting in at least one death. Spanish health authorities have confirmed 35 H1N1 cases in the Aragon region, 18 of whom are in intensive care. On 17 March 2014, three cases were confirmed with a possible fourth awaiting results occurring at the Centre for Addiction and Mental Health in Toronto , Ontario, Canada. With more than 300 infections and over 20 deaths, India's health ministry declared an outbreak "well under control" with "no reason to panic" in April 2012. According to the Indian Health Ministry , 31,974 cases of swine flu had been reported and 1,895 people had died from an outbreak by mid-March. Maldives reported swine flu in early 2017; [ better source needed ] 501 people were tested for the disease and 185 (37%) of those tested were positive for the disease. Four of those who tested positive from these 185 died due to this disease. The total number of people who have died due to the disease is unknown. Patient Zero was never identified. Schools were closed for a week due to the disease, but were ordered by the Ministry of Education to open after the holidays even though the disease was not fully under control. Myanmar reported H1N1 in late July 2017. As of 27 July, there were 30 confirmed cases and six people had died. The Ministry of Health and Sports of Myanmar sent an official request to WHO to provide help to control the virus; and also mentioned that the government would be seeking international assistance, including from the UN , China and the United States. Pakistan reported H1N1 cases mostly arising from the city of Multan , with deaths resulting from the epidemic reaching 42. There have also been confirmed cases in cities of Gujranwala and Lahore .An outbreak of swine flu in the European Union member state was reported in mid-January 2019, with the island's main state hospital overcrowded within a week, with more than 30 cases being treated. In January 2019 an outbreak of H1N1 was recorded in Morocco, with nine confirmed fatalities. In November 2019 an outbreak of H1N1 was recorded in Iran, with 56 fatalities and 4,000 people hospitalized. The G4 virus , also known as the "G4 swine flu virus" (G4) and "G4 EA H1N1", is a swine influenza virus strain discovered in China. The virus is a variant genotype 4 (G4) Eurasian avian-like (EA) H1N1 virus that mainly affects pigs, but there is some evidence of it infecting people. A 2020 peer-reviewed paper from the Proceedings of the National Academy of Sciences ( PNAS ) stated that "G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans ... Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring of swine working populations should be promptly implemented." Michael Ryan, executive director of the World Health Organization (WHO) Health Emergencies Program , stated in July 2020 that this strain of influenza virus was not new and had been under surveillance since 2011. The Chinese CDC said it had implemented an influenza surveillance program in 2010, analyzing more than 400,000 tests annually, to facilitate early identification of influenza. Of those, 13 A(H1N1) cases were detected, of which three were of the G4 variant. The study stated that almost 30,000 swine had been monitored via nasal swabs between 2011 and 2018. While other variants of the virus have appeared and diminished, the study claimed the G4 variant had sharply increased since 2016 to become the predominant strain. The Chinese Ministry of Agriculture and Rural Affairs rebutted the study, saying that the number of pigs sampled was too small to demonstrate G4 had become the dominant strain and that the media had interpreted the study "in an exaggerated and nonfactual way". They also said the infected workers "did not show flu symptoms and the test sample is not representative of the pig population in China". The US Centers for Disease Control and Prevention (CDC) said the study suggested that human infection by the G4 virus is more common than it was thought to be. Both the European Centre for Disease Prevention and Control (ECDC) and the US CDC stated that, like all flu viruses with pandemic potential, the variant is a concern that will be monitored. The ECDC stated that "the most important intervention in preparing for the pandemic potential of influenza viruses is the development and use of human vaccines ...". Health officials (including Anthony Fauci ) have said that the virus should be monitored, particularly among those in close contact with pigs, but it is not an immediate threat. While there have been no reported cases or evidence of the virus outside China as of July 2020, Smithsonian Magazine reported in July 2020 that scientists agree that the virus should be closely monitored , but because it "so far cannot jump from person to person", it should not be a cause for alarm yet. Pregnant women who contract the H1N1 infection are at greater risk of developing complications because of hormonal changes, physical changes and changes to their immune system to accommodate the growing fetus. For this reason the Centers for Disease Control and Prevention recommends that those who are pregnant be vaccinated to prevent the influenza virus. The vaccination should not be taken by people who have had a severe allergic reaction to the influenza vaccination. Those who are moderately to severely ill, with or without a fever should wait until they recover before vaccination. Pregnant women who become infected with the influenza are advised to contact their doctor immediately. Influenza can be treated with prescription antiviral medications. Oseltamivir (trade name Tamiflu) and zanamivir (Relenza) are two neuraminidase inhibitors (antiviral medications) recommended. They are most effective when taken within two days of becoming sick. Since 1 October 2008, the CDC has tested 1,146 seasonal influenza A (H1N1) viruses for resistance against oseltamivir and zanamivir. It was found that 99.6% of the samples were resistant to oseltamivir while none were resistant to zanamivir. After 2009 Influenza A (H1N1) virus samples were tested, only 4% (of 853 samples) showed resistance to oseltamivir (again, no samples showed resistance to zanamivir). A study conducted in Japan during the 2009 H1N1 pandemic concluded that infants exposed to either oseltamivir or zanamivir had no short term adverse effects. Both amantadine and rimantadine have been found to be teratogenic and embryotoxic (malformations and toxic effects on the embryo) when given at high doses in animal studies.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/1580_influenza_pandemic/html

1580 influenza pandemic

In 1580 a severe influenza pandemic was recorded on several continents. The virus originated in Asia and spread along the Silk Road through the Middle East into Europe and Africa , where newly established maritime trade routes and moving armies facilitated its worldwide spread. Contemporary historian Johann Boekel wrote that it spread over all of Europe in six weeks, in which thousands died and nearly everyone was infected. Those who witnessed the epidemic variously called the disease nicknames like coqueluche, Shaufkrankeit, castrone , or variations of catarrh or fever. Physicians of the time increasingly appreciated that "epidemic catarrhs" were being directly caused by a contagious agent instead of the stars or environment. The speed with which this disease propagated across societies and the symptoms strongly resembling influenza have been the basis for historians and academics to commonly identify this as a flu pandemic . Many contemporary epidemiologists consider this to be the first ever influenza pandemic. The epidemic has long been recognized as originating in Asia. The Italian historian Cesare Campana recorded in Delle Historie del Mundo (1599) that the "mal di Montone" quickly spread to the entirety of Africa and Europe. Infected travelers on the Silk Road brought the flu to the Levant , from whence it spread from the Ottoman Empire. The Spanish historian Antonio de Herrera y Tordesillas deduced that this epidemic most likely struck the Levant (then part of the Ottoman Empire) before hitting European cities in an east–west direction. Constantinople was being impacted by influenza in June. The Ottoman capital was a crucial Mediterranean port for shipping all varieties of goods, thus flu spread quickly to Ottoman territories in Europe, North Africa, and the Arabian Peninsula by ships. It immediately spread east to the ports of the Crimea , then north through Poland towards the Baltics. Influenza simultaneously spread though the empire's vast territory in southeastern Europe and infected the Republic of Venice by June. Catalan priest Pere Gil, who observed the epidemic spread, mentions that after passing through Western Europe that the disease rebounded into India. Constantinople was being impacted by influenza in June. The Ottoman capital was a crucial Mediterranean port for shipping all varieties of goods, thus flu spread quickly to Ottoman territories in Europe, North Africa, and the Arabian Peninsula by ships. It immediately spread east to the ports of the Crimea , then north through Poland towards the Baltics. Influenza simultaneously spread though the empire's vast territory in southeastern Europe and infected the Republic of Venice by June. Catalan priest Pere Gil, who observed the epidemic spread, mentions that after passing through Western Europe that the disease rebounded into India. Ottoman Algeria was a busy nexus for trade between North Africa and Europe. Flu traveled by infected merchants from the Ottoman to the Spanish Empires , which experienced outbreaks on the coast of North African in June. Spanish and Ottoman feuding had largely ended by 1580, enabling trade and travel between the two massive empires. Milanese physician Antonio Angelo Bellagatta believed that the 1580 flu caused widespread morbidity and mortality in Africa. Infected sailors had diffused influenza throughout the mediterranean to Spanish, Italian, and Maltese ports by late spring. Flu reached Europe in spring and quickly throughout the continent's interconnected Habsburg trade routes, where it triggered very large outbreaks that lasted from late June to mid October. In 1580, Europe was beset by wars that may have facilitated the spread of flu around Europe: Spain was dispatching soldiers to Portugal , Ireland , and the Netherlands , France was in a civil war , and Poland was preparing to invade Russia. Physicians called flu variations of febris , or fever, in their records such as morbus catarrhales , febris epidemica , or even febris pestilencia. The flu paralyzed armies and communities in outbreaks noted for their speed and universality, which in major cities lasted around 4 to 6 weeks and claimed thousands of lives. Influenza epidemics returned in waves until the fall of 1581. Portuguese chronicler Antonio de Herrera mentions that the disease struck Europe in Autumn. It spread "little by little" through Spain leaving citizens with severe headaches and coughing, runny noses, and long-lasting fevers. Sicily , then a vassal state of Spain, began seeing cases after possibly being introduced from Malta . Flu was being recorded in Catalonia at the beginning of August. André de Leones of Barcelona wrote that by September 7 all of his neighbors had experienced sickness. An estimated 20,000 of the city's residents had similarly falling ill in under two weeks during the height of the epidemic, with high numbers of casualties. Other Spanish cities were reportedly "depopulated" during the 1580 pandemic, which demonstrated an unusually high lethality for influenza. It was generally referred to in Spain as el catarro . Spanish royalty, nobility and clergy were significantly impacted. The Countess Doña Isabel de Castro died of the flu in Valladolid in August, followed by the Archbishop of Seville in September. King Philip II had given an order to send 40-50 Augustine and Franciscan priests to serve as ambassadors to newly discovered islands in the Philippines, but was only able to dispatch 34 due to the epidemic. According to the chronicler Jacques Auguste de Thou , the king himself became very ill and was attended to by his wife Anna of Austria, Queen of Spain . Anna contracted the flu during her pregnancy and it was seen as a contributing factor to her death on October 17. Influenza spread into the Spanish Netherlands quickly and early with cases recorded in Delft during June and July, likely brought by Spanish reinforcements sent to fight Dutch rebels. Ships from heavily affected Spain would have docked at the crowded port of Antwerp , from which flu likely spread to England . Cases continued to be reported in Spanish Netherlands well into October. Unlike in Rome and Madrid, the flu was not particularly fatal in the Netherlands . Portugal saw the arrival of influenza during the War of the Portuguese Succession . The Spanish-allied Duke of Alba wrote in letters that he "had it very mean with the catarrh" in Lisbon on September 2. As Philip II fought the flu, Antonio of Portugal organized 9000 soldiers in Coimbra and successfully suppressed support for the Duke of Alba. Campana recorded that the disease spread through Italy with the greatest intensity between August and September, and ascribed its cause to the damp and rainy spring prior. The Italian Kingdoms shared heavy trade with Habsburg Spain and the Republic of Venice shared a land border with the Ottoman Empire, entry points through which the flu invaded Italy early. Venice first recorded a flu epidemic on June 27 when writer Frederico Bujatto documented in Civil Acts a disease nicknamed moltone or montone , named for March's constellation Aries , spread throughout the city and featured a fever, cough, and headache for around 3 days. Influenza quickly spread through the communes of the Friuli region, such as Udine where an outbreak was recorded by the physician Gaspare Pratense. In Florence an outbreak of "male de Castrone" peaked during the first week of July. Rome's epidemic peaked in July, and its death toll was believed by some contemporaries to be as high as 10,000 (dubious as the city only had a population of around 100,000 at the time). By late July, the large numbers of people falling ill in Rome caught the attention of Pope Gregory XIII , who prohibited price-increases of goods during the epidemic, and Superior General Everard Mercurian of the Society of Jesus . Both ministered and cared for Rome's sick during the epidemic, causing them to contract the flu. Mercurian fell ill in late July and died on August 1, and the Pope was "on the edge of death" according to de Thou. On August 2 Lucrezia Gori, daughter of the popular composer Giovanni Palestrina , died suddenly amid Rome's epidemic. Nearly the entire city was infected (cite source) over the summer and out of a population of 80,000. 2000-9000 ultimately died of the flu within three months. Ineffective treatments such as bleeding and the exposure rates for clergy members, who continued to minister while sick, likely contributed to the city's high death toll. From the trading ports of Antwerp influenza reached England in early summer. It arrived in London , then a city of around 120,000 people in 1580, in early June and became widespread by July. London experienced significant excess mortalities during the flu epidemic, a period referred to as the "gentle correction" [by who or what] which lasted from late June to mid-August 1580. Reported overall weekly mortalities for London rose from 47 on June 30 to 77 on July 7 before rising to 133, 146, 96, and 78 deaths for the next four weeks respectively. According to a 1920s translation of the French Ambassador Michel de Castelnau 's letters, Queen Elizabeth fell ill with " whooping cough accompanied by a high fever" on July 5 as the flu was spreading throughout London. The modern French word for whooping cough, coqueluche, meant influenza in 1580. British physician Thomas Short wrote that "few died except those that were let blood of or had unsound viscera," indicating that the epidemic's outcome was not as severe in England as in Italy or Spain. Influenza was also spreading in Ireland. During the Desmond Rebellions an English force was seized by flu in August when over 300 soldiers fell ill in County Kerry while advancing to seize Tralee and Dingle . All survived. Amid civil war, influenza spread into the Kingdom of France during spring. Montpellier professor Lazare Rivière (1589–1655) believed the epidemic first arrived in the southern Languedoc region just after a locust plague in April and May. French physicians referred to flu as variations of febris or catharre but it was still casually referred to as coqueluche . Rivière described the "febris epidemica" of 1580 as featuring fever, coughing, headaches and back pain. Rivière observed that the disease spread rapidly and often resulted in death if the patient didn't recover within 5 days. From the coasts the virus spread instantly to Paris, even then a highly connected city with all varieties of travelers. Nicole Gilles recorded the "peste" of "coqueluche" in the city, which remained widespread into July. According to Pierre de L'Estoile , 10,000 Parisians fell ill from June 2 to June 8 alone including King Henry III , the Duke of Mercœur , and the Duke of Guise . At the direction of a sick Mercœur, Roch Le Baillif wrote and published Traicté du remede à la peste . The epidemic caused significant alarm in Paris, and rumors spread throughout the city of over 10,000 dying in Rome from "Coqueluche" in less than three months. Central France saw outbreaks documented in Poitiers and Orléans during July. Flu spread through France's south at the same time as the North, and likely through armies during the French Wars of Religion. Frederico Despalau and de Thou describe outbreaks of disease, possibly influenza, sickening both the royal army of King Henry III and the Duke of Biron 's opposing forces in early August, with military campaigns ending shortly thereafter in favor of the French King. Flu arrived in the Holy Roman Empire in summer after crossing from Italy, and had diffused throughout the country by fall. The epidemic's observers compared the symptoms and spread to epidemics of livestock, particularly sheep, and nicknamed flu 'chirp' (Zeip), 'sheep's cough' (Shaufthusten), and 'sheep's illness' (Shauftkrankeit). It appeared in Geneva at the beginning of June, the same time as Paris , and sickened many. German chronicler Johann Sporisch wrote in 1582 that the disease had "affected not only private houses, but also cities and entire kingdoms with such invasive ferocity," and described high fevers, fatigue, severe pain, pneumonia, and near-universal infection with the disease. Johan Boekle observed that the flu seemed to "spread over all of Europe in six weeks," although it most likely took around four months. Germany's larger cities were significantly impacted. Johan Boekle wrote that "In some places the sick fell into sweats, flowing more copiously in some than in others, so that a suspicion arose in the minds of some physicians of that English sweat which laid waste to the human race so horribly in 1529..." In Lübeck and Hamburg , thousands died. In September an outbreak was recorded at Schleswig-Holstein . Influenza spread from the Ottoman Empire through Poland from July to October, and was spreading in the Baltics within 4 months. At the time, the Polish–Lithuanian Commonwealth was engaged in the Livonian War against Russia. The Polish king dispatched a force of 48,000 men into Russia during the Battle of Velikiye Luki from September 1 to 5, whilst the flu was spreading in Poland. From Schleswig the epidemic spread quickly towards Denmark–Norway and Sweden , eventually spreading to even Iceland . Antonio Possevino , a papal diplomat on assignment in Sweden, wrote on the 25 June 1580 that some children playing around Stegeborg Castle fell sick with an epidemic illness, possibly flu. A new college outside Stockholm had to temporarily shut down due partly to the spreading epidemic. Portuguese chronicler Antonio de Herrera mentions that the disease struck Europe in Autumn. It spread "little by little" through Spain leaving citizens with severe headaches and coughing, runny noses, and long-lasting fevers. Sicily , then a vassal state of Spain, began seeing cases after possibly being introduced from Malta . Flu was being recorded in Catalonia at the beginning of August. André de Leones of Barcelona wrote that by September 7 all of his neighbors had experienced sickness. An estimated 20,000 of the city's residents had similarly falling ill in under two weeks during the height of the epidemic, with high numbers of casualties. Other Spanish cities were reportedly "depopulated" during the 1580 pandemic, which demonstrated an unusually high lethality for influenza. It was generally referred to in Spain as el catarro . Spanish royalty, nobility and clergy were significantly impacted. The Countess Doña Isabel de Castro died of the flu in Valladolid in August, followed by the Archbishop of Seville in September. King Philip II had given an order to send 40-50 Augustine and Franciscan priests to serve as ambassadors to newly discovered islands in the Philippines, but was only able to dispatch 34 due to the epidemic. According to the chronicler Jacques Auguste de Thou , the king himself became very ill and was attended to by his wife Anna of Austria, Queen of Spain . Anna contracted the flu during her pregnancy and it was seen as a contributing factor to her death on October 17. Influenza spread into the Spanish Netherlands quickly and early with cases recorded in Delft during June and July, likely brought by Spanish reinforcements sent to fight Dutch rebels. Ships from heavily affected Spain would have docked at the crowded port of Antwerp , from which flu likely spread to England . Cases continued to be reported in Spanish Netherlands well into October. Unlike in Rome and Madrid, the flu was not particularly fatal in the Netherlands . Portugal saw the arrival of influenza during the War of the Portuguese Succession . The Spanish-allied Duke of Alba wrote in letters that he "had it very mean with the catarrh" in Lisbon on September 2. As Philip II fought the flu, Antonio of Portugal organized 9000 soldiers in Coimbra and successfully suppressed support for the Duke of Alba. Campana recorded that the disease spread through Italy with the greatest intensity between August and September, and ascribed its cause to the damp and rainy spring prior. The Italian Kingdoms shared heavy trade with Habsburg Spain and the Republic of Venice shared a land border with the Ottoman Empire, entry points through which the flu invaded Italy early. Venice first recorded a flu epidemic on June 27 when writer Frederico Bujatto documented in Civil Acts a disease nicknamed moltone or montone , named for March's constellation Aries , spread throughout the city and featured a fever, cough, and headache for around 3 days. Influenza quickly spread through the communes of the Friuli region, such as Udine where an outbreak was recorded by the physician Gaspare Pratense. In Florence an outbreak of "male de Castrone" peaked during the first week of July. Rome's epidemic peaked in July, and its death toll was believed by some contemporaries to be as high as 10,000 (dubious as the city only had a population of around 100,000 at the time). By late July, the large numbers of people falling ill in Rome caught the attention of Pope Gregory XIII , who prohibited price-increases of goods during the epidemic, and Superior General Everard Mercurian of the Society of Jesus . Both ministered and cared for Rome's sick during the epidemic, causing them to contract the flu. Mercurian fell ill in late July and died on August 1, and the Pope was "on the edge of death" according to de Thou. On August 2 Lucrezia Gori, daughter of the popular composer Giovanni Palestrina , died suddenly amid Rome's epidemic. Nearly the entire city was infected (cite source) over the summer and out of a population of 80,000. 2000-9000 ultimately died of the flu within three months. Ineffective treatments such as bleeding and the exposure rates for clergy members, who continued to minister while sick, likely contributed to the city's high death toll.From the trading ports of Antwerp influenza reached England in early summer. It arrived in London , then a city of around 120,000 people in 1580, in early June and became widespread by July. London experienced significant excess mortalities during the flu epidemic, a period referred to as the "gentle correction" [by who or what] which lasted from late June to mid-August 1580. Reported overall weekly mortalities for London rose from 47 on June 30 to 77 on July 7 before rising to 133, 146, 96, and 78 deaths for the next four weeks respectively. According to a 1920s translation of the French Ambassador Michel de Castelnau 's letters, Queen Elizabeth fell ill with " whooping cough accompanied by a high fever" on July 5 as the flu was spreading throughout London. The modern French word for whooping cough, coqueluche, meant influenza in 1580. British physician Thomas Short wrote that "few died except those that were let blood of or had unsound viscera," indicating that the epidemic's outcome was not as severe in England as in Italy or Spain. Influenza was also spreading in Ireland. During the Desmond Rebellions an English force was seized by flu in August when over 300 soldiers fell ill in County Kerry while advancing to seize Tralee and Dingle . All survived. Amid civil war, influenza spread into the Kingdom of France during spring. Montpellier professor Lazare Rivière (1589–1655) believed the epidemic first arrived in the southern Languedoc region just after a locust plague in April and May. French physicians referred to flu as variations of febris or catharre but it was still casually referred to as coqueluche . Rivière described the "febris epidemica" of 1580 as featuring fever, coughing, headaches and back pain. Rivière observed that the disease spread rapidly and often resulted in death if the patient didn't recover within 5 days. From the coasts the virus spread instantly to Paris, even then a highly connected city with all varieties of travelers. Nicole Gilles recorded the "peste" of "coqueluche" in the city, which remained widespread into July. According to Pierre de L'Estoile , 10,000 Parisians fell ill from June 2 to June 8 alone including King Henry III , the Duke of Mercœur , and the Duke of Guise . At the direction of a sick Mercœur, Roch Le Baillif wrote and published Traicté du remede à la peste . The epidemic caused significant alarm in Paris, and rumors spread throughout the city of over 10,000 dying in Rome from "Coqueluche" in less than three months. Central France saw outbreaks documented in Poitiers and Orléans during July. Flu spread through France's south at the same time as the North, and likely through armies during the French Wars of Religion. Frederico Despalau and de Thou describe outbreaks of disease, possibly influenza, sickening both the royal army of King Henry III and the Duke of Biron 's opposing forces in early August, with military campaigns ending shortly thereafter in favor of the French King. Flu arrived in the Holy Roman Empire in summer after crossing from Italy, and had diffused throughout the country by fall. The epidemic's observers compared the symptoms and spread to epidemics of livestock, particularly sheep, and nicknamed flu 'chirp' (Zeip), 'sheep's cough' (Shaufthusten), and 'sheep's illness' (Shauftkrankeit). It appeared in Geneva at the beginning of June, the same time as Paris , and sickened many. German chronicler Johann Sporisch wrote in 1582 that the disease had "affected not only private houses, but also cities and entire kingdoms with such invasive ferocity," and described high fevers, fatigue, severe pain, pneumonia, and near-universal infection with the disease. Johan Boekle observed that the flu seemed to "spread over all of Europe in six weeks," although it most likely took around four months. Germany's larger cities were significantly impacted. Johan Boekle wrote that "In some places the sick fell into sweats, flowing more copiously in some than in others, so that a suspicion arose in the minds of some physicians of that English sweat which laid waste to the human race so horribly in 1529..." In Lübeck and Hamburg , thousands died. In September an outbreak was recorded at Schleswig-Holstein . Influenza spread from the Ottoman Empire through Poland from July to October, and was spreading in the Baltics within 4 months. At the time, the Polish–Lithuanian Commonwealth was engaged in the Livonian War against Russia. The Polish king dispatched a force of 48,000 men into Russia during the Battle of Velikiye Luki from September 1 to 5, whilst the flu was spreading in Poland. From Schleswig the epidemic spread quickly towards Denmark–Norway and Sweden , eventually spreading to even Iceland . Antonio Possevino , a papal diplomat on assignment in Sweden, wrote on the 25 June 1580 that some children playing around Stegeborg Castle fell sick with an epidemic illness, possibly flu. A new college outside Stockholm had to temporarily shut down due partly to the spreading epidemic. After spreading in Europe for six weeks the virus eventually crossed the Atlantic Ocean aboard infected sailors to the New World . Records of the epidemic in the New World remain scant, however, as observers in New Spain may have been distracted by a very severe series of cocoliztli epidemics that wiped out half of Mexico's population between 1576 and 1580. Antonio de Herrera mentions that the epidemic spread through the Indies in his series on Portugal's history, but doesn't go into detail.It was increasingly appreciated by European physicians of the time that rapidly-spreading epidemic catarrhs were not being caused by stars or temperatures, but some form of contagion. Bloodletting and purgation were recognized as unhelpful and dangerous by various contemporaries. Dutch physician Johann Weyer observed that "venesection" very frequently resulted in death, but that even though almost everyone was infected the disease only killed around one in a thousand. Thus, most treatments involved providing the body with medicine instead of attempting to remove humors (bodily fluids).

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Pandemic influenza

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Influenza A virus subtype H2N2

Influenza A virus subtype H2N2 ( A/H2N2 ) is a subtype of Influenza A virus . H2N2 has mutated into various strains including the " Asian flu " strain (now extinct in the wild), H3N2 , and various strains found in birds . It is also suspected of causing a human pandemic in 1889. The geographic spreading of the 1889 Russian flu has been studied and published. Some believe that the 1889–1890 Russian flu was caused by the influenzavirus A virus subtype H2N2, but the evidence is not conclusive. It is the earliest flu pandemic for which detailed records are available. More recently, there are speculations that it might have been caused by one of the coronaviruses first discovered in the 1960s. The "Asian Flu" was a category 2 flu pandemic outbreak of influenzavirus A that first appeared in Guizhou , China in early 1957 and lasted until 1958. The first cases were reported in Singapore in February 1957. In February 1957, a new influenza A (H2N2) virus emerged in East Asia, triggering a pandemic ("Asian Flu"). This H2N2 virus was composed of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes. It was first reported in Singapore in February 1957, Hong Kong in April 1957, and in coastal cities in the United States in summer 1957. Some authors believe it originated from mutation in wild ducks combining with a pre-existing human strain. Other authors are less certain. It reached Hong Kong by April, and US by June. Estimates of US and worldwide deaths caused by this pandemic varies widely depending on source; ranging from approximately 69,800 to 116,000 in the United States, and worldwide from 1 million to 4 million, with the World Health Organization (WHO) settling on "about 2 million," with an overall mortality rate of 0.6%. Asian Flu was of the H2N2 subtype (a notation that refers to the configuration of the hemagglutinin and neuraminidase proteins in the virus) of type A influenza, and an influenza vaccine was developed in 1957 to contain its outbreak. [ citation needed ] The Asian Flu strain later evolved via antigenic shift into H3N2 which caused a milder pandemic from 1968 to 1969. Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. From October 2004 to February 2005, approximately 3,700 test kits of the 1957 H2N2 virus were accidentally spread around the world from the College of American Pathologists (CAP). CAP assists laboratories in accuracy by providing unidentified samples of viruses ; private contractor Meridian Bioscience in Cincinnati , U.S. , chose the 1957 strain instead of one of the less deadly avian influenza virus subtypes. The 1957 H2N2 virus is considered deadly and the U.S. government called for the vials containing the strain to be destroyed. [ citation needed ]

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Pandemic influenza

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Pandemic severity index

The pandemic severity index ( PSI ) was a proposed classification scale for reporting the severity of influenza pandemics in the United States. The PSI was accompanied by a set of guidelines intended to help communicate appropriate actions for communities to follow in potential pandemic situations. Released by the United States Department of Health and Human Services (HHS) on February 1, 2007, the PSI was designed to resemble the Saffir-Simpson Hurricane Scale classification scheme. The index was replaced by the Pandemic Severity Assessment Framework in 2014, which uses quadrants based on transmissibility and clinical severity rather than a linear scale. The PSI was developed by the Centers for Disease Control and Prevention (CDC) as a new pandemic influenza planning tool for use by states, communities, businesses and schools, as part of a drive to provide more specific community-level prevention measures. Although designed for domestic implementation, the HHS has not ruled out sharing the index and guidelines with interested international parties. The index and guidelines were developed by applying principles of epidemiology to data from the history of the last three major flu pandemics and seasonal flu transmission, mathematical models, and input from experts and citizen focus groups. Many "tried and true" practices were combined in a more structured manner: We also realize as we look back through history is what cities did – 44 cities did, is that many of these measures ultimately every city adopted at some point or another, and the difference may be in the timing of using these measures and whether they're coordinated in an effective way for us to really gain the benefits of them.During the onset of a growing pandemic, local communities cannot rely upon widespread availability of antiviral drugs and vaccines (See Influenza research ). The goal of the index is to provide guidance as to what measures various organizations can enact that will slow down the progression of a pandemic, easing the burden of stress upon community resources while definite solutions, like drugs and vaccines, can be brought to bear on the situation. The CDC expects adoption of the PSI will allow early co-ordinated use of community mitigation measures to affect pandemic progression. The index focuses less on how likely a disease will spread worldwide – that is, become a pandemic – and more upon how severe the epidemic actually is. The main criterion used to measure pandemic severity will be case-fatality rate (CFR), the percentage of deaths out of the total reported cases of the disease. The actual implementation of PSI alerts was expected to occur after the World Health Organization (WHO) announces phase 6 influenza transmission (human to human) in the United States. This would probably result in immediate announcement of a PSI level 3–4 situation. The analogy of "category" levels were introduced to provide an understandable connection to hurricane classification schemes, with specific reference to the recent aftermath of Hurricane Katrina . Like the Saffir–Simpson Hurricane Scale , the PSI ranges from 1 to 5, with Category 1 pandemics being most mild (equivalent to seasonal flu ) and level 5 being reserved for the most severe "worst-case" scenario pandemics (such as the 1918 Spanish flu ). The report recommends four primary social distancing measures for slowing down a pandemic: Isolation and treatment of people who have suspected or confirmed cases of pandemic influenza Voluntary home quarantine of household contacts of those with suspected or confirmed pandemic influenza Dismissing school classes and closing daycare centers Changing work schedules and canceling large public gatherings These actions, when implemented, can have an overall effect of reducing the number of new cases of the disease; but they can carry potentially adverse consequences in terms of community and social disruption. The measures should have the most noticeable impact if implemented uniformly by organizations and governments across the US. While unveiling the PSI, Dr. Martin Cetron, Director for the Division of Global Migration and Quarantine at the CDC, reported that early feedback to the idea of a pandemic classification scale has been "uniformly positive". The University of Minnesota 's Center for Infectious Disease Research and Policy (CIDRAP) reports that the PSI has been "drawing generally high marks from public health officials and others, but they say the plan spells a massive workload for local planners". One MD praised that the PSI were "a big improvement over the previous guidance"; while historical influenza expert and author John M. Barry was more critical of the PSI, saying not enough emphasis was placed on basic health principles that could have an impact at the community level, adding "I'd feel a lot more comfortable with a lot more research [supporting them]". During the initial press releases in 2007, the CDC acknowledge that the PSI and the accompanying guidelines were a work in progress and will likely undergo revision in the months following their release. In 2014, after the 2009 swine flu pandemic , the PSI was replaced by the Pandemic Severity Assessment Framework , which uses quadrants based on transmissibility and clinical severity rather than a linear scale.

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Pandemic influenza

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Hong Kong flu

The Hong Kong flu , also known as the 1968 flu pandemic , was a flu pandemic that occurred in 1968 and 1969 and which killed between one and four million people globally. It is among the deadliest pandemics in history, and was caused by an H3N2 strain of the influenza A virus . The virus was descended from H2N2 (which caused the Asian flu pandemic in 1957–1958) through antigenic shift , a genetic process in which genes from multiple subtypes are reassorted to form a new virus. The first recorded instance of the outbreak appeared on 13 July 1968 in British Hong Kong . It has been speculated that the outbreak began in mainland China before it spread to Hong Kong; On 11 July, before the outbreak in the colony was first noted, the Hong Kong newspaper Ming Pao reported an outbreak of respiratory illness in Guangdong Province , and the next day, The Times issued a similar report of an epidemic in southeastern China. Later reporting suggested that the flu had spread from the central provinces of Sichuan , Gansu , Shaanxi , and Shanxi , which had experienced epidemics in the spring. However, due to a lack of etiological information on the outbreak and a strained relationship between Chinese health authorities and those in other countries at the time, it cannot be ascertained whether the Hong Kong virus was to blame. The outbreak in Hong Kong, where the population density was greater than 6,000 people per square kilometre (20,000 per sq. mi.), [ clarify ] reached its maximum intensity in two weeks. The outbreak lasted around six weeks, affecting about 15% of the population (some 500,000 people infected), but the mortality rate was low and the clinical symptoms were mild. There were two waves of the flu in mainland China, one between July–September in 1968 and the other between June–December in 1970. The reported data were very limited due to the Cultural Revolution , but retrospective analysis of flu activity between 1968 and 1992 shows that flu infection was the most serious in 1968, implying that most areas in China were affected at the time. Despite the lethality of the 1957–1958 pandemic in China , little improvement had been made regarding the handling of such epidemics. By 13 August, it was clear to virologists that strains isolated from the outbreak in Hong Kong differed markedly from previous strains of influenza. However, they were not at the time considered to be an entirely new subtype of influenza A, only a variant of older strains. Nevertheless, the World Health Organization warned of potential worldwide spread of the virus on 16 August. An outbreak of influenza-like illness in Singapore during the second week of August was the first indication of spread outside of Hong Kong. Around the same time, an outbreak became apparent in the Philippines and Malaysia , and, before the end of the month, an epidemic was underway in the Republic of Vietnam . The first known cases of the flu in the United Kingdom were identified in early August in an infant and her mother in London with no history of travel or known contact with anyone with a history of travel from the Far East. More isolated cases soon followed, but it was not until September that larger outbreaks began occurring in school settings. In September 1968, the flu reached India , northern Australia , Thailand , and Europe . The same month, the virus entered the United States and was carried by troops returning from the Vietnam War , but it did not become widespread in the country until December 1968. During the second week of September, nearly 2000 participants from 92 countries, including some in southeast Asia where the flu was epidemic, met in Tehran for the Eighth International Congresses on Tropical Medicine and Malaria. An outbreak of influenza soon erupted among the participants, afflicting at least a third of them. The convention was the apparent origin of a broader outbreak within the capital city, which thereafter spread rapidly throughout Iran . The virus entered Japan repeatedly throughout August and September, but these introductions did not spark any larger outbreak. The first "true epidemic" began in early October, almost entirely confined to school settings. In the USSR , the first cases of the flu began to appear in mid-December. It reached Africa and South America by 1969. The development of the pandemic at first resembled that of the 1957 pandemic, which had spread unencumbered throughout the spring and summer and had become truly worldwide by October, by which point nearly all countries were experiencing their first or even second wave. However, the two experiences eventually diverged within a couple of months after their initial outbreaks. In 1968, many countries (e.g., the UK, Japan) did not immediately see outbreaks despite repeated introductions of the virus throughout August and September. Additionally, after September, there was little evidence of continued spread in new areas, despite similar importations of the virus into those areas. Epidemics did eventually develop during the winter months, but these were often mild (especially when compared to the US experience). In some countries (such as the UK and Japan), it was not until the following winter of 1969–1970 that truly severe epidemics developed. At the time of the outbreak, the Hong Kong flu was also known as the "Mao flu" or " Mao Tse-tung flu". The name "Hong Kong flu" was not used within the colony, where the press dubbed it the "killer flu" after the first several deaths. Before the end of July, the South China Morning Post predicted that "Fingers of scorn" would be directed at Hong Kong in the coming weeks and stated that the colony had "acted, unwillingly, in our old role as an entrepot for a sneeze". (An outbreak of influenza in Hong Kong had been the first one to occur outside of mainland China during the 1957–1958 pandemic and had been what alerted the rest of the world to the developing situation, when international press began to report on it.) A city councillor [ who? ] later decried the widespread adoption of the name "Hong Kong flu", claiming that it was "giving Hong Kong a bad name". He asked why foreign press and health authorities did not refer to it by its "proper name—China flu". China certainly did not escape associations with the new virus, however, as the name "Mao flu" suggests. It was speculated even at the time that the virus had originated from "Red China". These differing names for the flu resulted in some confusion: In January 1969, a British member of parliament asked David Ennals , the Secretary of State for Social Services , "in what way the characteristics of Mao flu can be distinguished from those of Hong Kong flu". In addition to these names, the virus was also often referred to as "Asian flu" or "Asiatic flu", as it was not yet considered an entirely different subtype from the previously circulating influenza A. Worldwide deaths from the virus peaked in December 1968 and January 1969, when public health warnings and virus descriptions had been widely issued in the scientific and medical journals. Isolated countries like Albania reported the first cases of the flu in December 1969, reaching a peak in infections in the first months of the year 1970. In Berlin , the excessive number of deaths led to corpses being stored in subway tunnels, and in West Germany , garbage collectors had to bury the dead because of a lack of undertakers. In total, East and West Germany registered 60,000 estimated deaths. In some areas of France , half of the workforce was bedridden, and manufacturing suffered large disruptions because of absenteeism. The UK postal and rail services were also severely disrupted. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. It became apparent once the extent of antigenic variation in the virus was recognized that a new vaccine would be needed to protect against it. However, production of the previously recommended vaccines in the US had concluded by July 1968, and supply of fertilized chicken eggs, in which flu vaccines are grown , was limited. The first cultures of the virus were provided to manufacturers in August by the Division of Biologics of the National Institutes of Health for preliminary study. A strain isolated in Japan was sent to the US and, after showing greater potential for vaccine production, was given to manufacturers on 9 September. In 1968, American microbiologist Maurice Hilleman was head of the virus and vaccination research programs at the pharmaceutical firm Merck & Co. , one of the licensed vaccine manufacturers in the US. Hilleman, as the director of the Department of Respiratory Diseases at the Army Medical School (now the Walter Reed Army Institute of Research ), had foreseen the 1957 pandemic and kickstarted vaccine production then. He was similarly instrumental in the development of the 1968 pandemic vaccine and, with the use of the Japanese strain, helped initiate early production. Merck would go on to produce over 9 million of the nearly 21 million doses of vaccine produced. The other half was produced together by Eli Lilly & Co. , Lederle Laboratories , Parke Davis & Co. , the National Drug Company, and Wyeth Laboratories . All of these except Wyeth had been involved in the production of the 1957 vaccine. On 15 November, 66 days after the production strain became available, the first batch of 110,000 doses of vaccine was released, most of which went to the Armed Forces . This represented a quicker turnaround than the release of the first doses of the 1957 vaccine, which took three months after its production strain became available. At this time, the flu was spreading fast around the country. There was much interest within the press and among public figures in the vaccine. On 18 November, the Pharmaceutical Manufacturers Association announced that 17.5 million doses would be available for civilian use but said that "substantial quantities" would only come after the New Year. By the end of the year, over 10 million doses had been released. At this point, influenza was widespread in the country. Notably, the crew of Apollo 8 received the vaccine on 3 December prior to their mission later in the month. President Johnson received "two types" of vaccine prior to his bout of flu in December, but it is not clear if one of these was the pandemic vaccine. Johnson, 60 at the time, was in poor health and had been hospitalized several times during his presidency. He thus would have been prioritized for vaccine given the CDC recommendations, even outside of being the president. Lots of vaccine continued to be released throughout January 1969, with nearly 21 million doses available by the end of the month. By this point, however, influenza activity and subsequent mortality had already peaked. Demand for the vaccine diminished and a considerable surplus remained. Given the time it took to build up antibodies, it is unlikely a significant number of people were effectively immunized to alter the course of the epidemic. Hilleman himself would later acknowledge that the vaccine was "too little and too late" for most of the country. However, it was estimated that a "considerably higher" proportion of the recommended priority group of older and chronically ill persons received the pandemic vaccine than in 1957. Nevertheless, even after the debacle that was the vaccination effort in 1957 , US health officials by 1968 still had "no meaningful information regarding [influenza vaccine's] actual distribution", such as "to what extent it actually reaches persons at highest risk." Following the epidemic in the US, leftover vaccine was made available for the southern hemisphere and parts of Europe where the main outbreak had not yet happened. The Japanese strain of the new variant was incorporated into the bivalent vaccines recommended for the 1969–1970 flu season in the US. Outside the US, vaccination efforts were undertaken in many countries in anticipation of an epidemic. In contrast to US policy, Japan had, since 1963, carried out mass vaccination campaigns against influenza every year regardless of whether an epidemic was expected. This began with the immunization of all children in kindergartens and primary and secondary schools followed by the vaccination of those working in crowded conditions. Enough vaccine was produced each year to vaccinate about 24 million people (nearly a quarter of Japan's population at this time), and this became the goal in 1968, targeting the same priority groups as in a typical flu season. The same Japanese strain used for vaccine production in the US was immediately sent out to the seven manufacturing firms in Japan. It was soon decided a bivalent vaccine consisting of two parts the new variant and one part influenza B would be produced, in contrast to the US's use of monovalent vaccine. The objective was also set that enough vaccine to immunize about 12 million people would be produced by the end of October, with the hope of at least vaccinating children to guard against an epidemic developing out of schools. After some delay, the mass vaccination campaign was nearly completed before the end of the year. Yugoslavia received the Japanese strain in mid-October and immediately began experimental trials prior to large-scale production. During this time before the new vaccine was ready, 1.5 million doses of seasonal influenza A vaccine were distributed for use. Ten million doses of the pandemic vaccine had been produced by mid-January 1969, and nearly 1 million people were immunized before the end of February. About 100,000 doses were designated for the mass immunization of schoolchildren. In Denmark , the influenza department at the governmental Statens Serum Institut produced about 200,000 doses of pandemic vaccine during the winter of 1968–1969, incorporating a strain isolated in Stockholm . There were no particular difficulties in production, but yield was poor. Millions of doses of vaccine were available in South Africa before its epidemic began at the end of March 1969, which afforded the opportunity to perform "limited studies" of its effectiveness. By January 1969, vaccine production in Australia was underway at the Commonwealth Serum Laboratories (CSL), then a department of the federal government . The trivalent pandemic vaccine, composed of two influenza A strains and a B strain, was anticipated for release in early March ahead of the winter flu season. The inoculation consisted of a two-dose series, each given four weeks apart. CSL was aggressive in its promotion of the vaccine, at least to doctors. A spokesman for the laboratories described the new virus as "the worst flu we have had" and called an epidemic that year "almost certain". In light of the situation, the Australian Pensioners Federation in early January wrote to Minister for Health Jim Forbes "demanding" that the vaccine be given free of charge to pensioners. In contrast to CSL's bolder predictions, Forbes described an outbreak that winter as "possible" but did not think it would "necessarily be serious or extensive". While the Department of Health reviewed the question of pandemic vaccine allocation in Australia, the government exported 1 million doses of its vaccine to Britain, already at the peak of its epidemic. In early February, the epidemiology committee of Australia's National Health and Medical Research Council met in Melbourne to discuss the influenza threat and the best use of vaccine the coming winter. A "serious epidemic" was considered the "strongest possibility", and it was recommended to Forbes that older people, children, and pregnant women receive free immunization against the flu. However, the council advised against a mass vaccination campaign, citing the findings of its study which showed the unreliable protection against infection of the present vaccines, and considered it unwise to vaccinate healthy people while the limited supply could be better used to mitigate severe outcomes in at-risk groups. On the last day of February, the Pharmaceutical Benefits Advisory Committee met to consider the question of making the pandemic vaccine a pharmaceutical benefit for pensioners. Before the end of the week, Forbes announced that shots would be given for free to all pensioners and their dependents, representing about two-thirds of the three groups recommended for priority immunization. The policy would go into effect starting 1 April. Vaccination against the flu was recommended beginning 1 March, but issues surrounding availability of vaccine soon became apparent throughout the month. In response to Representative Gordon Scholes of Victoria , who had heard complaints from chemists unable to acquire vaccine, Forbes clarified that bulk orders from larger establishments would be met first. He relayed the expectation of the director of CSL that the present situation would be met once quantities of single doses became available in early April. In the middle of March, Forbes assured that all medical practitioners would be able to acquire the vaccine by the middle of April. He described the new type of flu as milder than that which Australia had typically seen each year. Representative Charles Jones of Newcastle later in the month questioned Forbes why his home city's order had not been filled. Forbes revealed the export of 1 million doses to Britain earlier in the year but assured that the order "did not delay, or in any way hinder, [the Commonwealth Serum Laboratories'] capacity to fill Australian orders" and that there would be enough supply to meet expected demand. By this time, 1,755,000 doses had been released, and production continued its pace of 200,000 doses per week. Despite these assurances from Forbes, the Director General of the Department of Health William Refshauge sent a letter on 9 April to all doctors in the country asking them not to vaccinate healthy people until at-risk groups in the community have been inoculated. Forbes reported meeting with the Commonwealth Serum Laboratories commission to discuss how to speed up distribution of vaccine. Two days later, the director of CSL, W. R. Lane, dismissed criticism of the supply situation from the New South Wales branch of the Australian Medical Association as "a lot of nonsense". Contradicting the laboratories' more forceful marketing earlier in the year, he downplayed the likelihood of a serious epidemic but shared the expectation of 4 million doses distributed by the end of May, eight times as much as the average annual total distribution of 500,000 vaccine doses. On 22 April, Forbes testified in the House of Representatives regarding the vaccine situation. He reported 2.5 million doses had been produced by this time since February. When asked by Representative Theo Nicholls of South Australia to consider importing vaccine to alleviate the present shortage, Forbes noted that the country had already imported the 150,000 doses available. He lamented CSL's recent subjection to a "good deal of abuse" regarding the "temporary shortages" around the country, repeating the comparison between the present production effort and the country's average annual distribution of only 500,000 doses. That same day, N. F. Keith, president of the Victorian branch of the Pharmacy Guild , called on CSL to explain the situation surrounding vaccine supply to the public, which was putting pressure on chemists due to the lack of vaccines. On 25 April, it was reported that the Department of Health had reimported the remaining vaccine from the order of 1 million that the government had exported to Britain in January. After being sent to Britain, packaged there, and then sent back to Australia, it was sold to doctors at a markup of nearly 50 percent. Doctors criticized the Department and CSL's poor planning with respect to vaccine supply and the decision to export vaccine to Britain when it had already reached the peak of its flu season. They also blamed the shortage on an overreaction by the public, a response which they considered largely due to public statements made by CSL and health officials. The Department later attributed the decision to reimport the vaccine to a desire to ensure a reliable supply for pensioners. It also denied any involvement in the commercial sales of vaccine, in response to reporting on price markups on the reimported vaccine, saying that all it did was authorize the reimportation and list the product as a pharmaceutical benefit. The government itself was paying the same for the reimported vaccine as it was for that being distributed by CSL. By the end of April, 2.8 million doses of vaccine had been produced and distributed, with no signs of production slowing down. 250,000 doses were now being produced each week, and nearly half a million more were anticipated for 2 May. The H3N2 virus displaced the previously circulating H2N2 virus, which first emerged in 1957, and returned during the following 1969–70 flu season, which resulted in a second, deadlier wave of deaths in Europe, Japan, and Australia. Following the season of intense activity in many countries in the Southern Hemisphere, there was relatively low incidence of flu the subsequent two global flu seasons, from October 1970 to September 1971. Influenza B was predominant in the north, causing extensive outbreaks in the United States, but minimal in the south. The Hong Kong virus, on the other hand, was responsible for some large outbreaks in the Southern Hemisphere, some most likely occurring in populations that had still not been exposed to the virus. It was during this period that the city of Coonoor , in India, experienced a "fairly extensive" outbreak, in July 1971. Samples of the virus responsible were collected but their significance was not immediately recognized. The virus did not immediately spread to other countries, or at least did not immediately cause outbreaks, but it was amid an epidemic in England in early 1972, fueled by more original strains, that a variant showing considerable antigenic drift was identified in one isolate tested out of over 700. It ultimately came to be designated A/England/42/72. It was soon recognized, by comparison with the strains isolated then, that this virus had been the one responsible for the epidemic in India. The novel variant did not immediately spread after that outbreak, and circulating strains largely continued to resemble quite closely the original Hong Kong virus through April 1972. In May, however, at the onset of the flu season in the Southern Hemisphere, epidemics caused by the variant struck Malaysia, Singapore, and Australia, though South Africa and South America were unaffected. The die seemingly cast, the novel variant went on to cause widespread outbreaks in the Northern Hemisphere, by which point US press had dubbed the bug " London flu ". It completely replaced the previous strains still resembling the original pandemic virus. In places such as the US and England and Wales, the 1972–1973 flu season was the deadliest since their respective deadliest waves of the pandemic between 1968 and 1970. Influenza A/H3N2 remains in circulation today as a strain of seasonal flu. The first recorded instance of the outbreak appeared on 13 July 1968 in British Hong Kong . It has been speculated that the outbreak began in mainland China before it spread to Hong Kong; On 11 July, before the outbreak in the colony was first noted, the Hong Kong newspaper Ming Pao reported an outbreak of respiratory illness in Guangdong Province , and the next day, The Times issued a similar report of an epidemic in southeastern China. Later reporting suggested that the flu had spread from the central provinces of Sichuan , Gansu , Shaanxi , and Shanxi , which had experienced epidemics in the spring. However, due to a lack of etiological information on the outbreak and a strained relationship between Chinese health authorities and those in other countries at the time, it cannot be ascertained whether the Hong Kong virus was to blame. The outbreak in Hong Kong, where the population density was greater than 6,000 people per square kilometre (20,000 per sq. mi.), [ clarify ] reached its maximum intensity in two weeks. The outbreak lasted around six weeks, affecting about 15% of the population (some 500,000 people infected), but the mortality rate was low and the clinical symptoms were mild. There were two waves of the flu in mainland China, one between July–September in 1968 and the other between June–December in 1970. The reported data were very limited due to the Cultural Revolution , but retrospective analysis of flu activity between 1968 and 1992 shows that flu infection was the most serious in 1968, implying that most areas in China were affected at the time. Despite the lethality of the 1957–1958 pandemic in China , little improvement had been made regarding the handling of such epidemics. By 13 August, it was clear to virologists that strains isolated from the outbreak in Hong Kong differed markedly from previous strains of influenza. However, they were not at the time considered to be an entirely new subtype of influenza A, only a variant of older strains. Nevertheless, the World Health Organization warned of potential worldwide spread of the virus on 16 August. An outbreak of influenza-like illness in Singapore during the second week of August was the first indication of spread outside of Hong Kong. Around the same time, an outbreak became apparent in the Philippines and Malaysia , and, before the end of the month, an epidemic was underway in the Republic of Vietnam . The first known cases of the flu in the United Kingdom were identified in early August in an infant and her mother in London with no history of travel or known contact with anyone with a history of travel from the Far East. More isolated cases soon followed, but it was not until September that larger outbreaks began occurring in school settings. In September 1968, the flu reached India , northern Australia , Thailand , and Europe . The same month, the virus entered the United States and was carried by troops returning from the Vietnam War , but it did not become widespread in the country until December 1968. During the second week of September, nearly 2000 participants from 92 countries, including some in southeast Asia where the flu was epidemic, met in Tehran for the Eighth International Congresses on Tropical Medicine and Malaria. An outbreak of influenza soon erupted among the participants, afflicting at least a third of them. The convention was the apparent origin of a broader outbreak within the capital city, which thereafter spread rapidly throughout Iran . The virus entered Japan repeatedly throughout August and September, but these introductions did not spark any larger outbreak. The first "true epidemic" began in early October, almost entirely confined to school settings. In the USSR , the first cases of the flu began to appear in mid-December. It reached Africa and South America by 1969. The development of the pandemic at first resembled that of the 1957 pandemic, which had spread unencumbered throughout the spring and summer and had become truly worldwide by October, by which point nearly all countries were experiencing their first or even second wave. However, the two experiences eventually diverged within a couple of months after their initial outbreaks. In 1968, many countries (e.g., the UK, Japan) did not immediately see outbreaks despite repeated introductions of the virus throughout August and September. Additionally, after September, there was little evidence of continued spread in new areas, despite similar importations of the virus into those areas. Epidemics did eventually develop during the winter months, but these were often mild (especially when compared to the US experience). In some countries (such as the UK and Japan), it was not until the following winter of 1969–1970 that truly severe epidemics developed. At the time of the outbreak, the Hong Kong flu was also known as the "Mao flu" or " Mao Tse-tung flu". The name "Hong Kong flu" was not used within the colony, where the press dubbed it the "killer flu" after the first several deaths. Before the end of July, the South China Morning Post predicted that "Fingers of scorn" would be directed at Hong Kong in the coming weeks and stated that the colony had "acted, unwillingly, in our old role as an entrepot for a sneeze". (An outbreak of influenza in Hong Kong had been the first one to occur outside of mainland China during the 1957–1958 pandemic and had been what alerted the rest of the world to the developing situation, when international press began to report on it.) A city councillor [ who? ] later decried the widespread adoption of the name "Hong Kong flu", claiming that it was "giving Hong Kong a bad name". He asked why foreign press and health authorities did not refer to it by its "proper name—China flu". China certainly did not escape associations with the new virus, however, as the name "Mao flu" suggests. It was speculated even at the time that the virus had originated from "Red China". These differing names for the flu resulted in some confusion: In January 1969, a British member of parliament asked David Ennals , the Secretary of State for Social Services , "in what way the characteristics of Mao flu can be distinguished from those of Hong Kong flu". In addition to these names, the virus was also often referred to as "Asian flu" or "Asiatic flu", as it was not yet considered an entirely different subtype from the previously circulating influenza A. Worldwide deaths from the virus peaked in December 1968 and January 1969, when public health warnings and virus descriptions had been widely issued in the scientific and medical journals. Isolated countries like Albania reported the first cases of the flu in December 1969, reaching a peak in infections in the first months of the year 1970. In Berlin , the excessive number of deaths led to corpses being stored in subway tunnels, and in West Germany , garbage collectors had to bury the dead because of a lack of undertakers. In total, East and West Germany registered 60,000 estimated deaths. In some areas of France , half of the workforce was bedridden, and manufacturing suffered large disruptions because of absenteeism. The UK postal and rail services were also severely disrupted. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. After a major epidemic of H2N2 during the 1967–1968 flu season that resulted in outbreaks in all but four states, the Communicable Disease Center (today the Centers for Disease Control and Prevention ) in June 1968 forecasted little or no activity in 1968–1969. The vaccines for the upcoming season would incorporate the then-circulating seasonal flu strains, and the CDC's recommendations for their use extended mainly to individuals in older age groups (over the age of 45) and the chronically ill. Following the outbreak in Hong Kong and the recognition that it had been caused by a new variant of influenza, the CDC on 4 September revised its prediction for the 1968–1969 season. An extensive outbreak across the country was now more likely. It repeated more strongly its recommendation that existing vaccines go only to those at highest risk and recommended vaccinating or revaccinating this group once the monovalent vaccine specific to the new variant became available. The first cases of the virus were reported in Atlanta on 2 September. The first was a Marine Corps major returning from Vietnam, who fell ill four days after arriving back in the US. Two days later, his wife, who had not left the country, fell ill as well. The first outbreak occurred in a Marine Corps school in San Diego that same week. Before the end of the week, influenza surveillance was heightened all across the country, and summaries of the data were thereafter reported regularly by the CDC each week in its Morbidity and Mortality Weekly Report . Further outbreaks among military personnel with connections to southeast Asia were soon to follow during the middle of September. Isolated cases, mostly in those recently returning from the Far East, seeded the virus across the country throughout September. The first outbreaks in the civilian population occurred in late September and in October, and activity increased markedly throughout November, affecting 21 states by Thanksgiving. The epidemic became widespread in December, involving all 50 states before the end of the year. Outbreaks occurred in colleges and hospitals, in some places the disease attacking upwards of 40% of their populations. Reports of absenteeism among students and nurses grew. Schools in Los Angeles , for example, reported rates ranging from 10 to 25%, compared to a typical 5 or 6%. The Greater New York Hospital Association reported absenteeism of 15 to 20% among staff and urged its members to impose visitor restrictions to safeguard patients. Institutions in many states dismissed their students early for the holidays. In New York and many other areas, holiday sales suffered mid-December, which affected retailers blamed on the flu epidemic (though inflation could have contributed to this as well). Economic activity was also hampered by high levels of industrial absenteeism. On 18 December, it was reported that President Johnson had been hospitalized at Bethesda Naval Hospital with flu-like symptoms, but whether the new variant was the cause of his illness was not made clear. He returned to the White House on 22 December. Vice President Humphrey was also reported to be ailing from the flu on the day Johnson's condition was revealed. Flu-like illness kept other senior governmental officials from their posts around this time, such as National Security Advisor Walt Rostow , Deputy White House Press Secretary Tom Johnson , and chairman of the Joint Chiefs of Staff General Earle Wheeler . On 23 December, it was reported that President-elect Nixon had been ill with the flu at his daughter 's wedding the day before. Nixon later claimed that "the wedding cured the flu." Peak influenza activity for most states most likely occurred in the latter half of December or early January, but the exact week was impossible to determine due to the holiday season. Activity declined throughout January. Excess pneumonia-influenza mortality passed the epidemic threshold during the first week of December and increased rapidly over the next month, peaking in the first half of January. It took until late March for mortality to return to normal levels. There was no second wave during this season. Following the epidemic of influenza A, outbreaks of influenza B began in late January and continued until late March. Mostly elementary-school children were affected. This influenza B activity fit within the pattern of epidemics every three to six years, but the 1968–1969 flu season became the first documented instance of two major influenza A epidemics to occur in successive seasons. Given the widespread epidemic levels of influenza A activity in 1968–1969, the CDC in June 1969 predicted little more than "sporadic cases" of influenza A in the 1969–1970 season. Influenza activity was indeed less than the preceding season, but there was "considerably more" than expected. The flu affected 48 states the following season but was widespread in only six, compared to 44 out of the 50 states in which activity was reported in 1968–1969. In October 1969, the CDC, alongside Emory University , collaborated with the WHO to host an international conference on the novel influenza in Atlanta. A wide range of topics was discussed, including the origin and path of the pandemic, the experiences of individual countries, and effective control measures, such as vaccination. It became apparent once the extent of antigenic variation in the virus was recognized that a new vaccine would be needed to protect against it. However, production of the previously recommended vaccines in the US had concluded by July 1968, and supply of fertilized chicken eggs, in which flu vaccines are grown , was limited. The first cultures of the virus were provided to manufacturers in August by the Division of Biologics of the National Institutes of Health for preliminary study. A strain isolated in Japan was sent to the US and, after showing greater potential for vaccine production, was given to manufacturers on 9 September. In 1968, American microbiologist Maurice Hilleman was head of the virus and vaccination research programs at the pharmaceutical firm Merck & Co. , one of the licensed vaccine manufacturers in the US. Hilleman, as the director of the Department of Respiratory Diseases at the Army Medical School (now the Walter Reed Army Institute of Research ), had foreseen the 1957 pandemic and kickstarted vaccine production then. He was similarly instrumental in the development of the 1968 pandemic vaccine and, with the use of the Japanese strain, helped initiate early production. Merck would go on to produce over 9 million of the nearly 21 million doses of vaccine produced. The other half was produced together by Eli Lilly & Co. , Lederle Laboratories , Parke Davis & Co. , the National Drug Company, and Wyeth Laboratories . All of these except Wyeth had been involved in the production of the 1957 vaccine. On 15 November, 66 days after the production strain became available, the first batch of 110,000 doses of vaccine was released, most of which went to the Armed Forces . This represented a quicker turnaround than the release of the first doses of the 1957 vaccine, which took three months after its production strain became available. At this time, the flu was spreading fast around the country. There was much interest within the press and among public figures in the vaccine. On 18 November, the Pharmaceutical Manufacturers Association announced that 17.5 million doses would be available for civilian use but said that "substantial quantities" would only come after the New Year. By the end of the year, over 10 million doses had been released. At this point, influenza was widespread in the country. Notably, the crew of Apollo 8 received the vaccine on 3 December prior to their mission later in the month. President Johnson received "two types" of vaccine prior to his bout of flu in December, but it is not clear if one of these was the pandemic vaccine. Johnson, 60 at the time, was in poor health and had been hospitalized several times during his presidency. He thus would have been prioritized for vaccine given the CDC recommendations, even outside of being the president. Lots of vaccine continued to be released throughout January 1969, with nearly 21 million doses available by the end of the month. By this point, however, influenza activity and subsequent mortality had already peaked. Demand for the vaccine diminished and a considerable surplus remained. Given the time it took to build up antibodies, it is unlikely a significant number of people were effectively immunized to alter the course of the epidemic. Hilleman himself would later acknowledge that the vaccine was "too little and too late" for most of the country. However, it was estimated that a "considerably higher" proportion of the recommended priority group of older and chronically ill persons received the pandemic vaccine than in 1957. Nevertheless, even after the debacle that was the vaccination effort in 1957 , US health officials by 1968 still had "no meaningful information regarding [influenza vaccine's] actual distribution", such as "to what extent it actually reaches persons at highest risk." Following the epidemic in the US, leftover vaccine was made available for the southern hemisphere and parts of Europe where the main outbreak had not yet happened. The Japanese strain of the new variant was incorporated into the bivalent vaccines recommended for the 1969–1970 flu season in the US. Outside the US, vaccination efforts were undertaken in many countries in anticipation of an epidemic. In contrast to US policy, Japan had, since 1963, carried out mass vaccination campaigns against influenza every year regardless of whether an epidemic was expected. This began with the immunization of all children in kindergartens and primary and secondary schools followed by the vaccination of those working in crowded conditions. Enough vaccine was produced each year to vaccinate about 24 million people (nearly a quarter of Japan's population at this time), and this became the goal in 1968, targeting the same priority groups as in a typical flu season. The same Japanese strain used for vaccine production in the US was immediately sent out to the seven manufacturing firms in Japan. It was soon decided a bivalent vaccine consisting of two parts the new variant and one part influenza B would be produced, in contrast to the US's use of monovalent vaccine. The objective was also set that enough vaccine to immunize about 12 million people would be produced by the end of October, with the hope of at least vaccinating children to guard against an epidemic developing out of schools. After some delay, the mass vaccination campaign was nearly completed before the end of the year. Yugoslavia received the Japanese strain in mid-October and immediately began experimental trials prior to large-scale production. During this time before the new vaccine was ready, 1.5 million doses of seasonal influenza A vaccine were distributed for use. Ten million doses of the pandemic vaccine had been produced by mid-January 1969, and nearly 1 million people were immunized before the end of February. About 100,000 doses were designated for the mass immunization of schoolchildren. In Denmark , the influenza department at the governmental Statens Serum Institut produced about 200,000 doses of pandemic vaccine during the winter of 1968–1969, incorporating a strain isolated in Stockholm . There were no particular difficulties in production, but yield was poor. Millions of doses of vaccine were available in South Africa before its epidemic began at the end of March 1969, which afforded the opportunity to perform "limited studies" of its effectiveness. By January 1969, vaccine production in Australia was underway at the Commonwealth Serum Laboratories (CSL), then a department of the federal government . The trivalent pandemic vaccine, composed of two influenza A strains and a B strain, was anticipated for release in early March ahead of the winter flu season. The inoculation consisted of a two-dose series, each given four weeks apart. CSL was aggressive in its promotion of the vaccine, at least to doctors. A spokesman for the laboratories described the new virus as "the worst flu we have had" and called an epidemic that year "almost certain". In light of the situation, the Australian Pensioners Federation in early January wrote to Minister for Health Jim Forbes "demanding" that the vaccine be given free of charge to pensioners. In contrast to CSL's bolder predictions, Forbes described an outbreak that winter as "possible" but did not think it would "necessarily be serious or extensive". While the Department of Health reviewed the question of pandemic vaccine allocation in Australia, the government exported 1 million doses of its vaccine to Britain, already at the peak of its epidemic. In early February, the epidemiology committee of Australia's National Health and Medical Research Council met in Melbourne to discuss the influenza threat and the best use of vaccine the coming winter. A "serious epidemic" was considered the "strongest possibility", and it was recommended to Forbes that older people, children, and pregnant women receive free immunization against the flu. However, the council advised against a mass vaccination campaign, citing the findings of its study which showed the unreliable protection against infection of the present vaccines, and considered it unwise to vaccinate healthy people while the limited supply could be better used to mitigate severe outcomes in at-risk groups. On the last day of February, the Pharmaceutical Benefits Advisory Committee met to consider the question of making the pandemic vaccine a pharmaceutical benefit for pensioners. Before the end of the week, Forbes announced that shots would be given for free to all pensioners and their dependents, representing about two-thirds of the three groups recommended for priority immunization. The policy would go into effect starting 1 April. Vaccination against the flu was recommended beginning 1 March, but issues surrounding availability of vaccine soon became apparent throughout the month. In response to Representative Gordon Scholes of Victoria , who had heard complaints from chemists unable to acquire vaccine, Forbes clarified that bulk orders from larger establishments would be met first. He relayed the expectation of the director of CSL that the present situation would be met once quantities of single doses became available in early April. In the middle of March, Forbes assured that all medical practitioners would be able to acquire the vaccine by the middle of April. He described the new type of flu as milder than that which Australia had typically seen each year. Representative Charles Jones of Newcastle later in the month questioned Forbes why his home city's order had not been filled. Forbes revealed the export of 1 million doses to Britain earlier in the year but assured that the order "did not delay, or in any way hinder, [the Commonwealth Serum Laboratories'] capacity to fill Australian orders" and that there would be enough supply to meet expected demand. By this time, 1,755,000 doses had been released, and production continued its pace of 200,000 doses per week. Despite these assurances from Forbes, the Director General of the Department of Health William Refshauge sent a letter on 9 April to all doctors in the country asking them not to vaccinate healthy people until at-risk groups in the community have been inoculated. Forbes reported meeting with the Commonwealth Serum Laboratories commission to discuss how to speed up distribution of vaccine. Two days later, the director of CSL, W. R. Lane, dismissed criticism of the supply situation from the New South Wales branch of the Australian Medical Association as "a lot of nonsense". Contradicting the laboratories' more forceful marketing earlier in the year, he downplayed the likelihood of a serious epidemic but shared the expectation of 4 million doses distributed by the end of May, eight times as much as the average annual total distribution of 500,000 vaccine doses. On 22 April, Forbes testified in the House of Representatives regarding the vaccine situation. He reported 2.5 million doses had been produced by this time since February. When asked by Representative Theo Nicholls of South Australia to consider importing vaccine to alleviate the present shortage, Forbes noted that the country had already imported the 150,000 doses available. He lamented CSL's recent subjection to a "good deal of abuse" regarding the "temporary shortages" around the country, repeating the comparison between the present production effort and the country's average annual distribution of only 500,000 doses. That same day, N. F. Keith, president of the Victorian branch of the Pharmacy Guild , called on CSL to explain the situation surrounding vaccine supply to the public, which was putting pressure on chemists due to the lack of vaccines. On 25 April, it was reported that the Department of Health had reimported the remaining vaccine from the order of 1 million that the government had exported to Britain in January. After being sent to Britain, packaged there, and then sent back to Australia, it was sold to doctors at a markup of nearly 50 percent. Doctors criticized the Department and CSL's poor planning with respect to vaccine supply and the decision to export vaccine to Britain when it had already reached the peak of its flu season. They also blamed the shortage on an overreaction by the public, a response which they considered largely due to public statements made by CSL and health officials. The Department later attributed the decision to reimport the vaccine to a desire to ensure a reliable supply for pensioners. It also denied any involvement in the commercial sales of vaccine, in response to reporting on price markups on the reimported vaccine, saying that all it did was authorize the reimportation and list the product as a pharmaceutical benefit. The government itself was paying the same for the reimported vaccine as it was for that being distributed by CSL. By the end of April, 2.8 million doses of vaccine had been produced and distributed, with no signs of production slowing down. 250,000 doses were now being produced each week, and nearly half a million more were anticipated for 2 May. The H3N2 virus displaced the previously circulating H2N2 virus, which first emerged in 1957, and returned during the following 1969–70 flu season, which resulted in a second, deadlier wave of deaths in Europe, Japan, and Australia. Following the season of intense activity in many countries in the Southern Hemisphere, there was relatively low incidence of flu the subsequent two global flu seasons, from October 1970 to September 1971. Influenza B was predominant in the north, causing extensive outbreaks in the United States, but minimal in the south. The Hong Kong virus, on the other hand, was responsible for some large outbreaks in the Southern Hemisphere, some most likely occurring in populations that had still not been exposed to the virus. It was during this period that the city of Coonoor , in India, experienced a "fairly extensive" outbreak, in July 1971. Samples of the virus responsible were collected but their significance was not immediately recognized. The virus did not immediately spread to other countries, or at least did not immediately cause outbreaks, but it was amid an epidemic in England in early 1972, fueled by more original strains, that a variant showing considerable antigenic drift was identified in one isolate tested out of over 700. It ultimately came to be designated A/England/42/72. It was soon recognized, by comparison with the strains isolated then, that this virus had been the one responsible for the epidemic in India. The novel variant did not immediately spread after that outbreak, and circulating strains largely continued to resemble quite closely the original Hong Kong virus through April 1972. In May, however, at the onset of the flu season in the Southern Hemisphere, epidemics caused by the variant struck Malaysia, Singapore, and Australia, though South Africa and South America were unaffected. The die seemingly cast, the novel variant went on to cause widespread outbreaks in the Northern Hemisphere, by which point US press had dubbed the bug " London flu ". It completely replaced the previous strains still resembling the original pandemic virus. In places such as the US and England and Wales, the 1972–1973 flu season was the deadliest since their respective deadliest waves of the pandemic between 1968 and 1970. Influenza A/H3N2 remains in circulation today as a strain of seasonal flu. Flu symptoms typically lasted four to five days, but some cases persisted for up to two weeks. The Hong Kong flu was the first known outbreak of the H3N2 strain, but there is serologic evidence of H3N1 infections in the late 19th century. The virus was isolated in Queen Mary Hospital . Soon after the initial outbreak in Hong Kong, the virus responsible was recognized to be antigenically distinct from the current influenza A strain in circulation (which at the time was called "A2") but was generally not considered an entirely new subtype. Analysis using the conventional techniques at the time revealed that it was indeed very different from older A2 viruses but also, at the same time, seemingly related to them, depending on one's reading of the data. Experiments involving newer methods of analysis soon identified another surface antigen, neuraminidase , in addition to hemagglutinin , which had already been recognized. It thus became clear that it was the hemagglutinin that had changed compared to older strains while the neuraminidase was identical. These findings, in part, prompted the World Health Organization in 1971 to revise its system of nomenclature for influenza viruses, taking into consideration both antigens. The novel virus was thereafter designated H3N2, indicating its partial similarity to H2N2 but also its antigenic distinction. The H3N2 pandemic flu strain contained genes from a low- pathogenicity avian influenza virus. Specifically, it had acquired a new hemagglutinin gene and a new PB1 gene, while it preserved the neuraminidase and five other genes from the preexisting human H2N2 strain. The new hemagglutinin helped H3N2 evade preexisting immunity in humans. It is possible that the new PB1 facilitated viral replication and human-to-human transmission. The new subtype arose in pigs coinfected with avian and human viruses and was soon transferred to humans. Swine were considered the original "intermediate host" for influenza because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (such as many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 , associated with the 1918 flu pandemic , may have been transmitted directly from birds to humans. Accumulated antibodies to the neuraminidase or internal proteins may have resulted in many fewer casualties than most other pandemics . However, cross-immunity within and between subtypes of influenza is poorly understood. [ citation needed ] The basic reproduction number of the flu in this period was estimated at 1.80. The estimates of the total death toll due to Hong Kong flu (from its beginning in July 1968 until the outbreak faded during the winter of 1969–70 ) vary: However, the death rate from the Hong Kong flu was lower than most other 20th-century pandemics. The World Health Organization estimated the case fatality rate of Hong Kong flu to be lower than 0.2%. The disease was allowed to spread through the population without restrictions on economic activity, and a vaccine created by American microbiologist Maurice Hilleman and his team became available four months after it had started. Fewer people died during this pandemic than in previous pandemics for several reasons: For this pandemic, there were two geographically distinct mortality patterns. In North America (the United States and Canada), the first pandemic season (1968–69) was more severe than the second (1969–70). In the "smoldering" pattern seen in Europe and Asia (United Kingdom, France, Japan, and Australia), the second pandemic season was two to five times more severe than the first. The United States health authorities estimated that about 34,000 to 100,000 people died in the US; most excess deaths were in those aged 65 and older. For this pandemic, there were two geographically distinct mortality patterns. In North America (the United States and Canada), the first pandemic season (1968–69) was more severe than the second (1969–70). In the "smoldering" pattern seen in Europe and Asia (United Kingdom, France, Japan, and Australia), the second pandemic season was two to five times more severe than the first. The United States health authorities estimated that about 34,000 to 100,000 people died in the US; most excess deaths were in those aged 65 and older.

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Pandemic influenza

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Pandemic

A pandemic ( / p æ n ˈ d ɛ m ɪ k / pan-DEM-ik ) is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. Widespread endemic diseases with a stable number of infected individuals such as recurrences of seasonal influenza are generally excluded as they occur simultaneously in large regions of the globe rather than being spread worldwide. Throughout human history , there have been a number of pandemics of diseases such as smallpox . The Black Death , caused by the Plague , wiped out up to half of the population of Europe in the 14th century. The term pandemic had not been used then, but was used for later epidemics, including the 1918 H1N1 influenza A pandemic—more commonly known as the Spanish flu —which is the deadliest pandemic in history . The most recent pandemics include the HIV/AIDS pandemic , [lower-alpha 1] the 2009 swine flu pandemic and the COVID-19 pandemic . Almost all these diseases still circulate among humans though their impact now is often far less. In response to the COVID-19 pandemic, 194 member states of the World Health Organization began negotiations on an International Treaty on Pandemic Prevention, Preparedness and Response , with a requirement to submit a draft of this treaty to the 77th World Health Assembly during its 2024 convention. A medical dictionary definition of pandemic is " an epidemic occurring on a scale that crosses international boundaries, usually affecting people on a worldwide scale ". A disease or condition is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, cancer is responsible for many deaths but is not considered a pandemic because the disease is not contagious —i.e. easily transmissible—and not even simply infectious . This definition differs from colloquial usage in that it encompasses outbreaks of relatively mild diseases. The World Health Organization (WHO) has a category of Public Health Emergency of International Concern , defined as " an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response ". There is a rigorous process underlying this categorization and a clearly defined trajectory of responses. A WHO-sponsored international body, tasked with preparing an international agreement on pandemic prevention, preparedness and response has defined a pandemic as " the global spread of a pathogen or variant that infects human populations with limited or no immunity through sustained and high transmissibility from person to person, overwhelming health systems with severe morbidity and high mortality, and causing social and economic disruptions, all of which require effective national and global collaboration and coordination for its control ". The word comes from the Greek παν- pan- meaning "all", or "every" and δῆμος demos "people". A common early characteristic of a pandemic is a rapid, sometimes exponential , growth in the number of infections, coupled with a widening geographical spread. WHO utilises different criteria to declare a Public Health Emergency of International Concern (PHEIC), its nearest equivalent to the term pandemic. The potential consequences of an incident are considered, rather than its current status. For example, polio was declared a PHEIC in 2014 even though only 482 cases were reported globally in the previous year; this was justified by concerns that polio might break out of its endemic areas and again become a significant health threat globally. The PHEIC status of polio is reviewed regularly and is ongoing, despite the small number of cases annually. [lower-alpha 2] The end of a pandemic is more difficult to delineate. Generally, past epidemics & pandemics have faded out as the diseases become accepted into people's daily lives and routines, becoming endemic . The transition from pandemic to endemic may be defined based on: - a high proportion of the global population having immunity (through either natural infection or vaccination) fewer deaths health systems step down from emergency status perceived personal risk is lessened restrictive measures such as travel restrictions removed less coverage in public media. An endemic disease is always present in a population, but at a relatively low and predictable level. There may be periodic spikes of infections or seasonality, (e.g. influenza ) but generally the burden on health systems is manageable. A common early characteristic of a pandemic is a rapid, sometimes exponential , growth in the number of infections, coupled with a widening geographical spread. WHO utilises different criteria to declare a Public Health Emergency of International Concern (PHEIC), its nearest equivalent to the term pandemic. The potential consequences of an incident are considered, rather than its current status. For example, polio was declared a PHEIC in 2014 even though only 482 cases were reported globally in the previous year; this was justified by concerns that polio might break out of its endemic areas and again become a significant health threat globally. The PHEIC status of polio is reviewed regularly and is ongoing, despite the small number of cases annually. [lower-alpha 2] The end of a pandemic is more difficult to delineate. Generally, past epidemics & pandemics have faded out as the diseases become accepted into people's daily lives and routines, becoming endemic . The transition from pandemic to endemic may be defined based on: - a high proportion of the global population having immunity (through either natural infection or vaccination) fewer deaths health systems step down from emergency status perceived personal risk is lessened restrictive measures such as travel restrictions removed less coverage in public media. An endemic disease is always present in a population, but at a relatively low and predictable level. There may be periodic spikes of infections or seasonality, (e.g. influenza ) but generally the burden on health systems is manageable. Pandemic prevention comprises activities such as anticipatory research and development of therapies and vaccines, as well as monitoring for pathogens and disease outbreaks which may have pandemic potential. Routine vaccination programs are a type of prevention strategy, holding back diseases such as influenza and polio which have caused pandemics in the past, and could do so again if not controlled. Prevention overlaps with preparedness which aims to curtail an outbreak and prevent it getting out of control - it involves strategic planning, data collection and modelling to measure the spread, stockpiling of therapies, vaccines, and medical equipment, as well as public health awareness campaigning. By definition, a pandemic involves many countries so international cooperation, data sharing, and collaboration are essential; as is universal access to tests and therapies. Collaboration - In response to the COVID-19 pandemic, WHO established a Pandemic Hub in September 2021 in Berlin, aiming to address weaknesses around the world in how countries detect, monitor and manage public health threats. The Hub's initiatives include using artificial intelligence to analyse more than 35,000 data feeds for indications of emerging health threats, as well as improving facilities and coordination between academic institutions and WHO member countries. Detection - In May 2023, WHO launched the International Pathogen Surveillance Network (IPSN) (hosted by the Pandemic Hub) aiming to detect and respond to disease threats before they become epidemics and pandemics, and to optimize routine disease surveillance. The network provides a platform to connect countries, improving systems for collecting and analysing samples of potentially harmful pathogens . Therapies and Vaccines - The Coalition for Epidemic Preparedness Innovations (CEPI) is developing a program to condense new vaccine development timelines to 100 days, a third of the time it took to develop a COVID-19 vaccine. CEPI aims to reduce global epidemic and pandemic risk by developing vaccines against known pathogens as well as enabling rapid response to Disease X . In the US, the National Institute of Allergy and Infectious Diseases (NIAID) has developed a Pandemic Preparedness Plan which focuses on identifying viruses of concern and developing diagnostics and therapies (including prototype vaccines) to combat them. Modeling is important to inform policy decisions. It helps to predict the burden of disease on healthcare facilities, the effectiveness of control measures, projected geographical spread, and timing and extent of future pandemic waves. Public Awareness involves disseminating reliable information, ensuring consistency on message, transparency, and steps to discredit misinformation . Stockpiling involves maintaining strategic stockpiles of emergency supplies such as personal protective equipment, drugs and vaccines, and equipment such as respirators. Many of these items have limited shelf life , so they require stock rotation even though they may be rarely used. The COVID-19 pandemic highlighted a number of ethical and political issues which must be considered during a pandemic. These included decisions about who should be prioritised for treatment while resources are scarce; whether or not to make vaccination compulsory; the timing and extent of constraints on individual liberty, how to sanction individuals who do not comply with emergency regulations, and the extent of international collaboration and resource sharing. The COVID-19 pandemic highlighted a number of ethical and political issues which must be considered during a pandemic. These included decisions about who should be prioritised for treatment while resources are scarce; whether or not to make vaccination compulsory; the timing and extent of constraints on individual liberty, how to sanction individuals who do not comply with emergency regulations, and the extent of international collaboration and resource sharing. The basic strategies in the control of an outbreak are containment and mitigation . Containment may be undertaken in the early stages of the outbreak, including contact tracing and isolating infected individuals to stop the disease from spreading to the rest of the population, other public health interventions on infection control, and therapeutic countermeasures such as vaccinations which may be effective if available. When it becomes apparent that it is no longer possible to contain the spread of the disease, management will then move on to the mitigation stage, in which measures are taken to slow the spread of the disease and mitigate its effects on society and the healthcare system. In reality, containment and mitigation measures may be undertaken simultaneously. A key part of managing an infectious disease outbreak is trying to decrease the epidemic peak, known as " flattening the curve ". This helps decrease the risk of health services being overwhelmed and provides more time for a vaccine and treatment to be developed. A broad group of non-pharmaceutical interventions may be taken to manage the outbreak. In a flu pandemic, these actions may include personal preventive measures such as hand hygiene, wearing face-masks, and self-quarantine; community measures aimed at social distancing such as closing schools and canceling mass gatherings; community engagement to encourage acceptance and participation in such interventions; and environmental measures such as cleaning of surfaces. Another strategy, suppression , requires more extreme long-term non-pharmaceutical interventions to reverse the pandemic by reducing the basic reproduction number to less than 1. The suppression strategy, which includes stringent population-wide social distancing, home isolation of cases, and household quarantine, was undertaken by China during the COVID-19 pandemic where entire cities were placed under lockdown; such a strategy may carry with it considerable social and economic costs. For a novel influenza virus , WHO previously applied a six-stage classification to delineate the process by which the virus moves from the first few infections in humans through to a pandemic. Starting with phase 1 (infections identified in animals only), it moves through phases of increasing infection and spread to phase 6 (pandemic). In February 2020, a WHO spokesperson clarified that the system is no longer in use. In 2014, the United States Centers for Disease Control and Prevention (CDC) introduced a framework for characterising the progress of an influenza pandemic titled the Pandemic Intervals Framework . The six intervals of the framework are as follows: investigation of cases of novel influenza, recognition of increased potential for ongoing transmission, initiation of a pandemic wave, acceleration of a pandemic wave, deceleration of a pandemic wave, and preparation for future pandemic waves. At the same time, the CDC adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of influenza pandemics. The PSAF rates the severity of an influenza outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. This tool was not applied during the COVID-19 pandemic. For a novel influenza virus , WHO previously applied a six-stage classification to delineate the process by which the virus moves from the first few infections in humans through to a pandemic. Starting with phase 1 (infections identified in animals only), it moves through phases of increasing infection and spread to phase 6 (pandemic). In February 2020, a WHO spokesperson clarified that the system is no longer in use. In 2014, the United States Centers for Disease Control and Prevention (CDC) introduced a framework for characterising the progress of an influenza pandemic titled the Pandemic Intervals Framework . The six intervals of the framework are as follows: investigation of cases of novel influenza, recognition of increased potential for ongoing transmission, initiation of a pandemic wave, acceleration of a pandemic wave, deceleration of a pandemic wave, and preparation for future pandemic waves. At the same time, the CDC adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of influenza pandemics. The PSAF rates the severity of an influenza outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. This tool was not applied during the COVID-19 pandemic. SARS-CoV-2 , a new strain of coronavirus , was first detected in the city of Wuhan, Hubei Province , China, in December 2019. The outbreak was characterized as a Public Health Emergency of International Concern (PHEIC) between January 2020 and May 2023 by WHO. The number of people infected with COVID-19 has reached more than 767 million worldwide, with a death toll of 6.9 million. [lower-alpha 3] It is considered likely that the virus will eventually become endemic and, like the common cold, cause less severe disease for most people. HIV/AIDS was first identified as a disease in 1981, and is an ongoing worldwide public health issue. Since then, HIV/AIDS has killed an estimated 40 million people with a further 630,000 deaths annually; 39 million people are currently living with HIV infection. [lower-alpha 4] HIV has a zoonotic origin, having originated in nonhuman primates in Central Africa and transferred to humans in the early 20th century. The most frequent mode of transmission of HIV is through sexual contact with an infected person. There may be a short period of mild, nonspecific symptoms followed by an asymptomatic (but nevertheless infectious) stage called clinical latency - without treatment, this stage can last between 3 and 20 years. The only way to detect infection is by means of a HIV test. There is no vaccine to prevent HIV infection, but the disease can be held in check by means of antiretroviral therapy . Historical accounts of epidemics are often vague or contradictory in describing how victims were affected. A rash accompanied by a fever might be smallpox, measles, scarlet fever, or varicella , and it is possible that epidemics overlapped, with multiple infections striking the same population at once. It is often impossible to know the exact causes of mortality, although ancient DNA studies can sometimes detect residues of certain pathogens. It is assumed that, prior to the neolithic revolution around 10,000 BC, disease outbreaks were limited to a single family or clan, and did not spread widely before dying out. The domestication of animals increased human-animal contact, increasing the possibility of zoonotic infections. The advent of agriculture, and trade between settled groups, made it possible for pathogens to spread widely. As population increased, contact between groups became more frequent. A history of epidemics maintained by the Chinese Empire from 243 B.C. to 1911 A.C. shows an approximate correlation between the frequency of epidemics and the growth of the population. Here is an incomplete list of known epidemics which spread widely enough to merit the title "pandemic". Beginning from the Middle Ages, encounters between European settlers and native populations in the rest of the world often introduced epidemics of extraordinary virulence. Settlers introduced novel diseases which were endemic in Europe, such as smallpox , measles , pertussis .and influenza , to which the indigenous peoples had no immunity. The Europeans infected with such diseases typically carried them in a dormant state , were actively infected but asymptomatic , or had only mild symptoms. Smallpox was the most destructive disease that was brought by Europeans to the Native Americans, both in terms of morbidity and mortality. The first well-documented smallpox epidemic in the Americas began in Hispaniola in late 1518 and soon spread to Mexico. Estimates of mortality range from one-quarter to one-half of the population of central Mexico. It is estimated that over the 100 years after European arrival in 1492, the indigenous population of the Americas dropped from 60 million to only 6 million, due to a combination of disease, war, and famine. The majority these deaths are attributed to successive waves of introduced diseases such as smallpox, measles, and typhoid fever. In Australia , smallpox was introduced by European settlers in 1789 devastating the Australian Aboriginal population, killing an estimated 50% of those infected with the disease during the first decades of colonisation. In the early 1800s, measles, smallpox and intertribal warfare killed an estimated 20,000 New Zealand Māori . In 1848–49, as many as 40,000 out of 150,000 Hawaiians are estimated to have died of measles , whooping cough and influenza . Measles killed more than 40,000 Fijians , approximately one-third of the population, in 1875, and in the early 19th century devastated the Great Andamanese population. In Hokkaido , an epidemic of smallpox introduced by Japanese settlers is estimated to have killed 34% of the native Ainu population in 1845. SARS-CoV-2 , a new strain of coronavirus , was first detected in the city of Wuhan, Hubei Province , China, in December 2019. The outbreak was characterized as a Public Health Emergency of International Concern (PHEIC) between January 2020 and May 2023 by WHO. The number of people infected with COVID-19 has reached more than 767 million worldwide, with a death toll of 6.9 million. [lower-alpha 3] It is considered likely that the virus will eventually become endemic and, like the common cold, cause less severe disease for most people. HIV/AIDS was first identified as a disease in 1981, and is an ongoing worldwide public health issue. Since then, HIV/AIDS has killed an estimated 40 million people with a further 630,000 deaths annually; 39 million people are currently living with HIV infection. [lower-alpha 4] HIV has a zoonotic origin, having originated in nonhuman primates in Central Africa and transferred to humans in the early 20th century. The most frequent mode of transmission of HIV is through sexual contact with an infected person. There may be a short period of mild, nonspecific symptoms followed by an asymptomatic (but nevertheless infectious) stage called clinical latency - without treatment, this stage can last between 3 and 20 years. The only way to detect infection is by means of a HIV test. There is no vaccine to prevent HIV infection, but the disease can be held in check by means of antiretroviral therapy . SARS-CoV-2 , a new strain of coronavirus , was first detected in the city of Wuhan, Hubei Province , China, in December 2019. The outbreak was characterized as a Public Health Emergency of International Concern (PHEIC) between January 2020 and May 2023 by WHO. The number of people infected with COVID-19 has reached more than 767 million worldwide, with a death toll of 6.9 million. [lower-alpha 3] It is considered likely that the virus will eventually become endemic and, like the common cold, cause less severe disease for most people. HIV/AIDS was first identified as a disease in 1981, and is an ongoing worldwide public health issue. Since then, HIV/AIDS has killed an estimated 40 million people with a further 630,000 deaths annually; 39 million people are currently living with HIV infection. [lower-alpha 4] HIV has a zoonotic origin, having originated in nonhuman primates in Central Africa and transferred to humans in the early 20th century. The most frequent mode of transmission of HIV is through sexual contact with an infected person. There may be a short period of mild, nonspecific symptoms followed by an asymptomatic (but nevertheless infectious) stage called clinical latency - without treatment, this stage can last between 3 and 20 years. The only way to detect infection is by means of a HIV test. There is no vaccine to prevent HIV infection, but the disease can be held in check by means of antiretroviral therapy . Historical accounts of epidemics are often vague or contradictory in describing how victims were affected. A rash accompanied by a fever might be smallpox, measles, scarlet fever, or varicella , and it is possible that epidemics overlapped, with multiple infections striking the same population at once. It is often impossible to know the exact causes of mortality, although ancient DNA studies can sometimes detect residues of certain pathogens. It is assumed that, prior to the neolithic revolution around 10,000 BC, disease outbreaks were limited to a single family or clan, and did not spread widely before dying out. The domestication of animals increased human-animal contact, increasing the possibility of zoonotic infections. The advent of agriculture, and trade between settled groups, made it possible for pathogens to spread widely. As population increased, contact between groups became more frequent. A history of epidemics maintained by the Chinese Empire from 243 B.C. to 1911 A.C. shows an approximate correlation between the frequency of epidemics and the growth of the population. Here is an incomplete list of known epidemics which spread widely enough to merit the title "pandemic".Beginning from the Middle Ages, encounters between European settlers and native populations in the rest of the world often introduced epidemics of extraordinary virulence. Settlers introduced novel diseases which were endemic in Europe, such as smallpox , measles , pertussis .and influenza , to which the indigenous peoples had no immunity. The Europeans infected with such diseases typically carried them in a dormant state , were actively infected but asymptomatic , or had only mild symptoms. Smallpox was the most destructive disease that was brought by Europeans to the Native Americans, both in terms of morbidity and mortality. The first well-documented smallpox epidemic in the Americas began in Hispaniola in late 1518 and soon spread to Mexico. Estimates of mortality range from one-quarter to one-half of the population of central Mexico. It is estimated that over the 100 years after European arrival in 1492, the indigenous population of the Americas dropped from 60 million to only 6 million, due to a combination of disease, war, and famine. The majority these deaths are attributed to successive waves of introduced diseases such as smallpox, measles, and typhoid fever. In Australia , smallpox was introduced by European settlers in 1789 devastating the Australian Aboriginal population, killing an estimated 50% of those infected with the disease during the first decades of colonisation. In the early 1800s, measles, smallpox and intertribal warfare killed an estimated 20,000 New Zealand Māori . In 1848–49, as many as 40,000 out of 150,000 Hawaiians are estimated to have died of measles , whooping cough and influenza . Measles killed more than 40,000 Fijians , approximately one-third of the population, in 1875, and in the early 19th century devastated the Great Andamanese population. In Hokkaido , an epidemic of smallpox introduced by Japanese settlers is estimated to have killed 34% of the native Ainu population in 1845. Prevention of future pandemics requires steps to identify future causes of pandemics and to take preventive measures before the disease moves uncontrollably into the human population. For example, influenza is a rapidly evolving disease which has caused pandemics in the past and has potential to cause future pandemics. WHO collates the findings of 144 national influenza centres worldwide which monitor emerging flu viruses. Virus variants which are assessed as likely to represent a significant risk are identified and can then be incorporated into the next seasonal influenza vaccine program. In a press conference on 28 December 2020, Mike Ryan, head of the WHO Emergencies Program, and other officials said the current COVID-19 pandemic is "not necessarily the big one" and "the next pandemic may be more severe." They called for preparation. WHO and the UN have warned the world must tackle the cause of pandemics and not just the health and economic symptoms. There is always a possibility that a disease which has caused epidemics in the past may return in the future. It is also possible that little known diseases may become more virulent; in order to encourage research, a number of organisations which monitor global health have drawn up lists of diseases which may have pandemic potential; see table below. [lower-alpha 5] Coronavirus diseases are a family of usually mild illnesses in humans, including those such as the common cold , that have resulted in outbreaks and pandemics such as the 1889-1890 pandemic , the 2002–2004 SARS outbreak , Middle East respiratory syndrome–related coronavirus and the COVID-19 pandemic . There is widespread concern that members of the coronavirus family, particularly SARS and MERS have the potential to cause future pandemics. Many human coronaviruses have zoonotic origin, their with natural reservoir in bats or rodents, leading to concerns for future spillover events. Following the end of the COVID-19 pandemic Public Health Emergency of International Concern deceleration by WHO, WHO Director General Tedros Ghebreyesus stated he would not hesitate to re-declare COVID-19 a PHEIC should the global situation worsen in the coming months or years. Influenza was first described by the Greek physician Hippocrates in 412 BC. Since the Middle Ages, influenza pandemics have been recorded every 10 to 30 years as the virus mutates to evade immunity. Influenza is an endemic disease , with a fairly constant number of cases which vary seasonally and can, to a certain extent, be predicted. In a typical year, 5–15% of the population contracts influenza. There are 3–5 million severe cases annually, with up to 650,000 respiratory-related deaths globally each year. The 1889–1890 pandemic is estimated to have caused around a million fatalities, and the " Spanish flu " of 1918–1920 eventually infected about one-third of the world's population and caused an estimate 50 million fatalities. The Global Influenza Surveillance and Response System is a global network of laboratories that has for purpose to monitor the spread of influenza with the aim to provide WHO with influenza control information. More than two million respiratory specimens are tested by GISRS annually to monitor the spread and evolution of influenza viruses through a network of about 150 laboratories in 114 countries representing 91% of the world's population. Antibiotic-resistant microorganisms, which sometimes are referred to as " superbugs ", may contribute to the re-emergence of diseases with pandemic potential that are currently well controlled. For example, cases of tuberculosis that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. China and India have the highest rate of MDR-TB. WHO reports that approximately 50 million people worldwide are infected with MDR-TB, with 79 percent of those cases resistant to three or more antibiotics. Extensively drug-resistant tuberculosis ( XDR-TB ) was first identified in Africa in 2006 and subsequently discovered to exist in 49 countries. During 2021 there were estimated to be around 25,000 cases XDR-TB worldwide. In the past 20 years, other common bacteria including Staphylococcus aureus , Serratia marcescens and Enterococcus , have developed resistance to a wide range of antibiotics . Antibiotic-resistant organisms have become an important cause of healthcare-associated ( nosocomial ) infections. There are two groups of infectious disease that may be affected by climate change. The first group are vector-borne diseases which are transmitted via insects such as mosquitos or ticks. Some of these diseases, such as malaria , yellow fever , and dengue fever , can have potentially severe health consequences. Climate can affect the distribution of these diseases due to the changing geographic range of their vectors, with the potential to cause serious outbreaks in areas where the disease has not previously been known. The other group comprises water-borne diseases such as cholera, dysentery, and typhoid which may increase in prevalence due to changes in rainfall patterns. The October 2020 'era of pandemics' report by the United Nations ' Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services , written by 22 experts in a variety of fields, said the anthropogenic destruction of biodiversity is paving the way to the pandemic era and could result in as many as 850,000 viruses being transmitted from animals—in particular birds and mammals —to humans. The "exponential rise" in consumption and trade of commodities such as meat , palm oil , and metals, largely facilitated by developed nations, and a growing human population , are the primary drivers of this destruction. According to Peter Daszak , the chair of the group who produced the report, "there is no great mystery about the cause of the Covid-19 pandemic or any modern pandemic. The same human activities that drive climate change and biodiversity loss also drive pandemic risk through their impacts on our environment." Proposed policy options from the report include taxing meat production and consumption, cracking down on the illegal wildlife trade, removing high-risk species from the legal wildlife trade, eliminating subsidies to businesses that are harmful to the natural world, and establishing a global surveillance network. In June 2021, a team of scientists assembled by the Harvard Medical School Center for Health and the Global Environment warned that the primary cause of pandemics so far, the anthropogenic destruction of the natural world through such activities including deforestation and hunting , is being ignored by world leaders. Permafrost covers a fifth of the northern hemisphere and is made up of soil that has been kept at temperatures below freezing for long periods. Viable samples of viruses have been recovered from thawing permafrost, after having been frozen for many years, sometimes for millennia. There is a remote possibility that a thawed pathogen could infect humans or animals. There is always a possibility that a disease which has caused epidemics in the past may return in the future. It is also possible that little known diseases may become more virulent; in order to encourage research, a number of organisations which monitor global health have drawn up lists of diseases which may have pandemic potential; see table below. [lower-alpha 5] Coronavirus diseases are a family of usually mild illnesses in humans, including those such as the common cold , that have resulted in outbreaks and pandemics such as the 1889-1890 pandemic , the 2002–2004 SARS outbreak , Middle East respiratory syndrome–related coronavirus and the COVID-19 pandemic . There is widespread concern that members of the coronavirus family, particularly SARS and MERS have the potential to cause future pandemics. Many human coronaviruses have zoonotic origin, their with natural reservoir in bats or rodents, leading to concerns for future spillover events. Following the end of the COVID-19 pandemic Public Health Emergency of International Concern deceleration by WHO, WHO Director General Tedros Ghebreyesus stated he would not hesitate to re-declare COVID-19 a PHEIC should the global situation worsen in the coming months or years. Influenza was first described by the Greek physician Hippocrates in 412 BC. Since the Middle Ages, influenza pandemics have been recorded every 10 to 30 years as the virus mutates to evade immunity. Influenza is an endemic disease , with a fairly constant number of cases which vary seasonally and can, to a certain extent, be predicted. In a typical year, 5–15% of the population contracts influenza. There are 3–5 million severe cases annually, with up to 650,000 respiratory-related deaths globally each year. The 1889–1890 pandemic is estimated to have caused around a million fatalities, and the " Spanish flu " of 1918–1920 eventually infected about one-third of the world's population and caused an estimate 50 million fatalities. The Global Influenza Surveillance and Response System is a global network of laboratories that has for purpose to monitor the spread of influenza with the aim to provide WHO with influenza control information. More than two million respiratory specimens are tested by GISRS annually to monitor the spread and evolution of influenza viruses through a network of about 150 laboratories in 114 countries representing 91% of the world's population. Coronavirus diseases are a family of usually mild illnesses in humans, including those such as the common cold , that have resulted in outbreaks and pandemics such as the 1889-1890 pandemic , the 2002–2004 SARS outbreak , Middle East respiratory syndrome–related coronavirus and the COVID-19 pandemic . There is widespread concern that members of the coronavirus family, particularly SARS and MERS have the potential to cause future pandemics. Many human coronaviruses have zoonotic origin, their with natural reservoir in bats or rodents, leading to concerns for future spillover events. Following the end of the COVID-19 pandemic Public Health Emergency of International Concern deceleration by WHO, WHO Director General Tedros Ghebreyesus stated he would not hesitate to re-declare COVID-19 a PHEIC should the global situation worsen in the coming months or years.Influenza was first described by the Greek physician Hippocrates in 412 BC. Since the Middle Ages, influenza pandemics have been recorded every 10 to 30 years as the virus mutates to evade immunity. Influenza is an endemic disease , with a fairly constant number of cases which vary seasonally and can, to a certain extent, be predicted. In a typical year, 5–15% of the population contracts influenza. There are 3–5 million severe cases annually, with up to 650,000 respiratory-related deaths globally each year. The 1889–1890 pandemic is estimated to have caused around a million fatalities, and the " Spanish flu " of 1918–1920 eventually infected about one-third of the world's population and caused an estimate 50 million fatalities. The Global Influenza Surveillance and Response System is a global network of laboratories that has for purpose to monitor the spread of influenza with the aim to provide WHO with influenza control information. More than two million respiratory specimens are tested by GISRS annually to monitor the spread and evolution of influenza viruses through a network of about 150 laboratories in 114 countries representing 91% of the world's population. Antibiotic-resistant microorganisms, which sometimes are referred to as " superbugs ", may contribute to the re-emergence of diseases with pandemic potential that are currently well controlled. For example, cases of tuberculosis that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. China and India have the highest rate of MDR-TB. WHO reports that approximately 50 million people worldwide are infected with MDR-TB, with 79 percent of those cases resistant to three or more antibiotics. Extensively drug-resistant tuberculosis ( XDR-TB ) was first identified in Africa in 2006 and subsequently discovered to exist in 49 countries. During 2021 there were estimated to be around 25,000 cases XDR-TB worldwide. In the past 20 years, other common bacteria including Staphylococcus aureus , Serratia marcescens and Enterococcus , have developed resistance to a wide range of antibiotics . Antibiotic-resistant organisms have become an important cause of healthcare-associated ( nosocomial ) infections. There are two groups of infectious disease that may be affected by climate change. The first group are vector-borne diseases which are transmitted via insects such as mosquitos or ticks. Some of these diseases, such as malaria , yellow fever , and dengue fever , can have potentially severe health consequences. Climate can affect the distribution of these diseases due to the changing geographic range of their vectors, with the potential to cause serious outbreaks in areas where the disease has not previously been known. The other group comprises water-borne diseases such as cholera, dysentery, and typhoid which may increase in prevalence due to changes in rainfall patterns. The October 2020 'era of pandemics' report by the United Nations ' Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services , written by 22 experts in a variety of fields, said the anthropogenic destruction of biodiversity is paving the way to the pandemic era and could result in as many as 850,000 viruses being transmitted from animals—in particular birds and mammals —to humans. The "exponential rise" in consumption and trade of commodities such as meat , palm oil , and metals, largely facilitated by developed nations, and a growing human population , are the primary drivers of this destruction. According to Peter Daszak , the chair of the group who produced the report, "there is no great mystery about the cause of the Covid-19 pandemic or any modern pandemic. The same human activities that drive climate change and biodiversity loss also drive pandemic risk through their impacts on our environment." Proposed policy options from the report include taxing meat production and consumption, cracking down on the illegal wildlife trade, removing high-risk species from the legal wildlife trade, eliminating subsidies to businesses that are harmful to the natural world, and establishing a global surveillance network. In June 2021, a team of scientists assembled by the Harvard Medical School Center for Health and the Global Environment warned that the primary cause of pandemics so far, the anthropogenic destruction of the natural world through such activities including deforestation and hunting , is being ignored by world leaders. Permafrost covers a fifth of the northern hemisphere and is made up of soil that has been kept at temperatures below freezing for long periods. Viable samples of viruses have been recovered from thawing permafrost, after having been frozen for many years, sometimes for millennia. There is a remote possibility that a thawed pathogen could infect humans or animals. In 2016, the commission on a Global Health Risk Framework for the Future estimated that pandemic disease events would cost the global economy over $6 trillion in the 21st century—over $60 billion per year. The same report recommended spending $4.5 billion annually on global prevention and response capabilities to reduce the threat posed by pandemic events, a figure that the World Bank Group raised to $13 billion in a 2019 report. It has been suggested that such costs be paid from a tax on aviation rather than from, e.g., income taxes, given the crucial role of air traffic in transforming local epidemics into pandemics (being the only factor considered in state-of-the-art models of long-range disease transmission ). The COVID-19 pandemic is expected to have a profound negative effect on the global economy , potentially for years to come, with substantial drops in GDP accompanied by increases in unemployment noted around the world. The slowdown of economic activity early in the COVID-19 pandemic had a profound effect on emissions of pollutants and greenhouse gases. Analysis of ice cores taken from the Swiss Alps have revealed a reduction in atmospheric lead pollution over a four-year period corresponding to the years 1349 to 1353 (when the Black Death was ravaging Europe), indicating a reduction in mining and economic activity generally.

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Pandemic influenza

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Influenza A virus subtype H5N1

Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type A of subtype H5N1 , is the highly pathogenic causative agent of H5N1 flu , commonly known as avian influenza ("bird flu"). It is enzootic (maintained in the population) in many bird populations, especially in Southeast Asia . One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Many references to "bird flu" and H5N1 in the popular media refer to this strain. According to the World Health Organization (WHO) and the United Nations Food and Agriculture Organization (FAO), H5N1 pathogenicity is gradually continuing to rise in endemic areas, but the avian influenza disease situation in farmed birds is being held in check by vaccination, and there is "no evidence of sustained human-to-human transmission" of the virus. Eleven outbreaks of H5N1 were reported worldwide in June 2008, in five countries (China, Egypt, Indonesia, Pakistan and Vietnam) compared to 65 outbreaks in June 2006, and 55 in June 2007. The global HPAI situation significantly improved in the first half of 2008, but FAO reports that imperfect disease surveillance systems mean that occurrence of the virus remains underestimated and underreported. As of March 2024, the WHO reported a total of 888 confirmed human cases which resulted in the deaths of 463 people since 2003. Several H5N1 vaccines have been developed and approved, and stockpiled by a number of countries, including the United States (in its National Stockpile ), Britain, France, Canada, and Australia, for use in an emergency. HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans has been characterized as inefficient. Still, around 60% of humans known to have been infected with the Asian strain of HPAI A(H5N1) have died from it, and H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. In 2003, virologist Robert G. Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist . He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives. On September 29, 2005, David Nabarro , the newly appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people. Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large host reservoir, and its significant ongoing mutations, in 2006, the H5N1 virus has been regarded to be the world's largest pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic . At least 12 companies and 17 governments are developing prepandemic influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly one. Full-scale production of a vaccine that could prevent any illness at all from the strain would require at least three months after the virus's emergence to begin, but it is hoped that vaccine production could increase until one billion doses were produced by one year after the initial identification of the virus. H5N1 may cause more than one influenza pandemic , as it is expected to continue mutating in birds regardless of whether humans develop herd immunity to a future pandemic strain. Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1. While genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the Spanish flu pandemic, planning for a future influenza pandemic is based on what can be done and there is no higher Pandemic Severity Index level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad as the Spanish flu or worse; and for which all intervention measures are to be used. In general, humans who catch a humanized influenza A virus (a human flu virus of type A) usually have symptoms that include fever , cough , sore throat , muscle aches , conjunctivitis , and, in severe cases, breathing problems and pneumonia that may be fatal. The severity of the infection depends in large part on the state of the infected persons' immune systems and whether they had been exposed to the strain before (in which case they would be partially immune). No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu. The avian influenza hemagglutinin binds alpha 2–3 sialic acid receptors, while human influenza hemagglutinins bind alpha 2–6 sialic acid receptors. This means when the H5N1 strain infects humans, it will replicate in the lower respiratory tract, and consequently will cause viral pneumonia . There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1. The reported mortality rate of highly pathogenic H5N1 avian influenza in a human is high; WHO data indicate 60% of cases classified as H5N1 resulted in death. However, there is some evidence the actual mortality rate of avian flu could be much lower, as there may be many people with milder symptoms who do not seek treatment and are not counted. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. There have been studies of the levels of cytokines in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha , a protein associated with tissue destruction at sites of infection and increased production of other cytokines. Flu virus-induced increases in the level of cytokines is also associated with flu symptoms, including fever, chills, vomiting and headache. Tissue damage associated with pathogenic flu virus infection can ultimately result in death. The inflammatory cascade triggered by H5N1 has been called a ' cytokine storm ' by some, because of what seems to be a positive feedback process of damage to the body resulting from immune system stimulation. H5N1 induces higher levels of cytokines than the more common flu virus types. Clinical signs of H5N1 in birds range from mild—decrease in egg production, nasal discharge, coughing and sneezing—to severe, including loss of coordination, energy, and appetite; soft-shelled or misshapen eggs; purple discoloration of the wattles, head, eyelids, combs, and hocks; and diarrhea. Sometimes the first noticeable sign is sudden death. Clinical signs of H5N1 in birds range from mild—decrease in egg production, nasal discharge, coughing and sneezing—to severe, including loss of coordination, energy, and appetite; soft-shelled or misshapen eggs; purple discoloration of the wattles, head, eyelids, combs, and hocks; and diarrhea. Sometimes the first noticeable sign is sudden death. The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959, but that strain was very different from the highly pathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype. It has also been called "Asian lineage HPAI A(H5N1)". Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam , Thailand , and Cambodia and bird isolates from Laos and Malaysia . Clade 2 viruses were first identified in bird isolates from China , Indonesia , Japan , and South Korea before spreading westward to the Middle East , Europe , and Africa . The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Map A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia." H5N1 isolates are identified like this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1) : Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/ shoveler /Egypt/03(H5N2). As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent , and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds. This [ which? ] deadly strain of H5N1 is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus . [ failed verification ] H5N1 is a subtype of the species Influenza A virus of the genus Alphainfluenzavirus of the family Orthomyxoviridae . Like all other influenza A subtypes, the H5N1 subtype is an RNA virus . It has a segmented genome of eight negative sense, single-strands of RNA , abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS. [ citation needed ] HA codes for hemagglutinin , an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase , an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells. The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies . HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1 . Low pathogenic avian influenza H5N1 (LPAI H5N1), also called "North American" H5N1, commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain. 1966 – LPAI H5N1 A/Turkey/Ontario/6613/1966(H5N1) was detected in a flock of infected turkeys in Ontario, Canada. 1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin. 1981 and 1985 – LPAI H5N1 was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time. 1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania. 1986 – LPAI H5N1 was detected in a wild mallard duck in Ohio. 2005 – LPAI H5N1 was detected in ducks in Manitoba, Canada. 2008 – LPAI H5N1 was detected in ducks in New Zealand. 2009 – LPAI H5N1 was detected in commercial poultry in British Columbia. "In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health ( OIE ) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets." Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses . The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time. A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic. [ citation needed ] The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans. [ citation needed ] Influenza A virus subtype H3N2 is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2 , which is now resistant to the standard antiviral drugs amantadine and rimantadine . The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2 . Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source". H5N1 isolates are identified like this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1) : Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/ shoveler /Egypt/03(H5N2). As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent , and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds. This [ which? ] deadly strain of H5N1 is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus . [ failed verification ]H5N1 is a subtype of the species Influenza A virus of the genus Alphainfluenzavirus of the family Orthomyxoviridae . Like all other influenza A subtypes, the H5N1 subtype is an RNA virus . It has a segmented genome of eight negative sense, single-strands of RNA , abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS. [ citation needed ] HA codes for hemagglutinin , an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase , an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells. The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies . HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1 .Low pathogenic avian influenza H5N1 (LPAI H5N1), also called "North American" H5N1, commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain. 1966 – LPAI H5N1 A/Turkey/Ontario/6613/1966(H5N1) was detected in a flock of infected turkeys in Ontario, Canada. 1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin. 1981 and 1985 – LPAI H5N1 was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time. 1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania. 1986 – LPAI H5N1 was detected in a wild mallard duck in Ohio. 2005 – LPAI H5N1 was detected in ducks in Manitoba, Canada. 2008 – LPAI H5N1 was detected in ducks in New Zealand. 2009 – LPAI H5N1 was detected in commercial poultry in British Columbia. "In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health ( OIE ) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets." Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses . The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different strains of influenza viruses at the same time. A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic. [ citation needed ] The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans. [ citation needed ] Influenza A virus subtype H3N2 is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2 , which is now resistant to the standard antiviral drugs amantadine and rimantadine . The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2 . Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source". There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Daniel R. Lucey , co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine ". However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain. "The United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Department of State , the U.S. Department of Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government". Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness". Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention , the World Health Organization , the European Commission , and others. There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Daniel R. Lucey , co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine ". However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain."The United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Department of State , the U.S. Department of Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government". Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness". Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention , the World Health Organization , the European Commission , and others. There is no highly effective treatment for H5N1 flu, but oseltamivir (commercially marketed by Roche as Tamiflu) can sometimes inhibit the influenza virus from spreading inside the user's body. This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic. On April 20, 2006, Roche AG announced that a stockpile of three million treatment courses of Tamiflu are waiting at the disposal of the World Health Organization to be used in case of a flu pandemic; separately Roche donated two million courses to the WHO for use in developing nations that may be affected by such a pandemic but lack the ability to purchase large quantities of the drug. However, WHO expert Hassan al-Bushra has said: Animal and lab studies suggest that Relenza ( zanamivir ), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. In a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1 , and H5N1 transmissible to mammals". In addition, mice studies suggest the combination of zanamivir, celecoxib and mesalazine looks promising producing a 50% survival rate compared to no survival in the placebo arm. While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can be manufactured in quantities that would be meaningful once efficient human transmission starts. In September, 2006, a WHO scientist announced that studies had confirmed cases of H5N1 strains resistant to Tamiflu and Amantadine. Tamiflu-resistant strains have also appeared in the EU , which remain sensitive to Relenza. The earliest infections of humans by H5N1 coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population in 1997. This panzootic (a disease affecting animals of many species, especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. However, the disease has continued to spread; outbreaks were reported in Asia again in 2003. On December 21, 2009, the WHO announced a total of 447 cases which resulted in the deaths of 263. H5N1 is easily transmissible between birds, facilitating a potential global spread of H5N1 . While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around the alveoli , structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission. H5N1 is mainly spread by domestic poultry , both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks , geese and swans ) carry H5N1, often without becoming sick. Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown. According to a report by the World Health Organization , H5N1 may be spread indirectly. The report stated the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people. H5N1 has mutated into a variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift , H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all belong to genotype Z of avian influenza virus H5N1, now the dominant genotype. H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002, new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks . This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961. Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1 that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997. Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations occurring within this genotype are increasing their pathogenicity. Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus. Infected birds transmit H5N1 through their saliva , nasal secretions , feces and blood . Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C (32 °F) (over one month at freezing temperature) or 6 days at 37 °C (99 °F) (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it does not degrade at all. Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry. In October 2004, researchers discovered H5N1 is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading this highly pathogenic strain to chickens , crows , pigeons , and other birds, and the virus was increasing its ability to infect mammals, as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic. "Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability." The New York Times , in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important". On September 29, 2007, researchers reported the H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells. In May 2013, North Korea confirmed a H5N1 bird flu outbreak that forced authorities to kill over 160,000 ducks in Pyongyang . A major outbreak of a new strain of H5N1 in wild birds and poultry appeared in Russia in August 2020 and quickly spread to other parts of Europe by October. Over the winter of 2021 and 2022 avian flu spread among the population of barnacle geese on the Solway Firth, UK, with estimates of up to a third of the Svalbard population being lost; pink-footed geese were also affected there and it seems carried the virus to new sites in northern Scotland. The disease was confirmed in sandwich terns in South Africa in April 2022. In late spring 2022 avian flu outbreaks affected many species of wild bird in the United Kingdom, with heavy losses reported among seabirds returning to breed at colonies in the Northern Isles and Outer Hebrides, including great skuas (bonxie) for which outbreaks had initially been reported in 2021 (Scotland hosts c. 60% of the world's breeding population) – the 2022 census on St Kilda showed a 64% decline on 2019 with 106 dead birds recorded so far (to 6 June), gannets (1000+ birds reported dead at the Shetlands' Hermaness colony alone, where there are around 26,000 breeding pairs), with many more gannets being reported dead at other colonies ( Troup Head , Bass Rock , and St Kilda ); the range of species also seems to be expanding, with reports for many species of wildfowl, seabirds (auks, terns and gulls) and scavenging species (corvids and raptors). Elsewhere in Europe the virus killed hundreds (574+) of Dalmatian pelicans in Greece, and in Israel around 6000 common cranes were found dead at Hula in December 2021. A report by Scientific Task Force on Avian Influenza and Wild Birds on: "H5N1 Highly Pathogenic Avian Influenza in poultry and wild birds: Winter of 2021/2022 with focus on mass mortality of wild birds in UK and Israel" summarises the situation up to 24 January 2022 and mentions that "H5N8 HPAI is still responsible for poultry and wild bird cases mainly in Asia, H5N1 has now in effect replaced this subtype in Africa and Eurasia in both poultry and wild birds". The 2022–2023 season was also the worst recorded outbreak in the United Kingdom, with the British government requiring a so-called "poultry lockdown" which required that farmers keep their birds indoors. Meanwhile, an outbreak of H5N1 on a Spanish mink farm led researchers to believe that they had observed the first case of mammal-to-mammal transmission of H5N1. Human cases were reported in Spain in November 2022, and in the UK in May 2023. By November 2020, large outbreaks of the new strain of H5N1 had started to spread into wild birds and farmed poultry across Asia. In February 2023, human cases were reported in Cambodia. Large losses of poultry and wild birds to H5N1 started to occur in Africa in November 2021 and continued through 2022. Similar to 2021 reports, outbreaks were noted from gannet colonies in Canada, with thousands of birds dead in June 2022, as well as common eiders and great black-backed gulls . Prior to that there were reports of spread in wild birds in over 30 states in the US, including major mortalities in a double-crested cormorant colony in Barrington, Illinois , the virus also spreading to scavengers including three bald eagles in Georgia. Mass die-offs of both birds and mammals were noted in Peru during the 2022–2023 season. In particular, the Peruvian government reported the deaths of approximately 63,000 birds as well as 716 sea lions , with the WHO noting that mammalian spillovers needed to be "monitored closely". In the United States, the 2022–2023 avian outbreak was the worst since H5N1 was first detected. Ecuador entered into a three-month "animal-health emergency" on 29 November 2022, just days after its first case was reported, whereas Argentina and Uruguay both declared "national sanitary emergencies" on 15 February 2023, after their respective first cases were discovered. On 22 May 2023, Brazil, as the world's largest exporter of chicken meat, declared a 180-day emergency following several cases detected in wild birds and created an emergency operations center to plan for and mitigate potential further spread of H5N1. Human cases were reported in Ecuador and Chile. In March 2024, H5N1 infections were recorded for the first time in deceased and sick livestock located in the United States. Goats and cows in three states became ill after exposure to wild birds and culled poultry. In early April, H5N1 was reported to have spread amongst dairy cow herds in multiple states of the USA, indicating cow-to-cow spread. A dairy worker in Texas also became infected, with conjunctivitis being the main symptom. H5N1 was detected in dead birds on the Antarctic mainland for the first time in February 2024. Novel, contagious strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011. Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times. After these 10 passages the H5N1 virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets. After Fouchier offered an article describing this work to the leading academic journal Science , the US National Science Advisory Board for Biosecurity (NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers. However, then the Dutch government declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods. [note 1] After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit for submitting his manuscript, and his research appeared in a special issue of the journal Science devoted to H5N1. The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible. In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute in Harbin , China, had created H5N1 strains which passed between guinea pigs . In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks of creating novel potential pandemic pathogens, culminating in the formation of the Cambridge Working Group , a consensus statement calling for an assessment of the risks and benefits of such research. Although mammals, including humans, had become infected with H5N1 bird flu strains in the past, these cases had ostensibly been caused by direct exposure to infected birds, such as through consumption of birds by wildlife or exposure to infected poultry by farmers. In contrast, the October 2022 mammalian outbreak of H5N1 on a Spanish mink farm showed evidence of being the first recorded case of mammal-to-mammal transmission, with 4 percent of the farm's mink population dying from H5N1-related haemorrhagic pneumonia. The mink respiratory tract is particularly well suited to act as a pathway of viral transmission into humans, which has concerned public health professionals due to the production of all but one approved human vaccine requiring the eggs of chickens, which H5N1 kills at a 90–100 percent fatality rate. Infected mink in Spain were also found to have exhibited the "PB2" viral mutation found when H5N1 jumped into pigs over a decade prior, adding to fears that farms could be acting as incubators and/or reservoirs of the virus, similar to the role of minks in SARS-CoV-2 . As of January 2023, fifteen species of wild and captive mammals had become infected with H5N1 throughout the United States. A mass Caspian seal die-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia's Dagestan republic , worried researchers regarding the possibility that wild mammal-to-mammal spread had begun. A similar mass die-off of 95% of southern elephant seal pups in 2023 also raised concerns of mammal-to-mammal spread, as nursing pups would have had less exposure to birds. In April 2024, spread of H5N1 amongst dairy cow herds in five states of the USA strongly indicated the presence of cow-to-cow transmission. As of April 2024, the WHO reported a total of 889 confirmed human cases which resulted in the deaths of 463 people since 2003. [ failed verification ] Following the February 2023 H5N1 death of an 11-year-old girl from Cambodia 's Prey Veng province , her father was confirmed positive for the virus and several close contacts also began showing signs of infection. On 24 February 2023, the WHO expressed concern that the virus had potentially begun to spread among humans and ordered the production of a new human vaccine for H5N1. Following the confirmed infections, the WHO began working with the Cambodian government to determine whether both individuals had gotten the virus directly from infected poultry or if it had indeed been a case of human-to-human transmission. Further sequencing determined that at least one of the two cases was from an older H5N1 clade, 2.3.2.1c, which had circulated as a common H5N1 strain in Cambodia for many years, rather than the more recent clade 2.3.4.4b, which had caused mass poultry deaths since 2020. This older clade had jumped to humans in the past yet hadn't previously resulted in any known human-to-human transmission. On March 1, 2023, as Taiwan raised its travel alert for Cambodia, the WHO and the U.S. CDC, in concert with Cambodian authorities, determined that both of the individuals had been infected through direct contact with poultry. H5N1 is easily transmissible between birds, facilitating a potential global spread of H5N1 . While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around the alveoli , structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission. H5N1 is mainly spread by domestic poultry , both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks , geese and swans ) carry H5N1, often without becoming sick. Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown. According to a report by the World Health Organization , H5N1 may be spread indirectly. The report stated the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people. H5N1 has mutated into a variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift , H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all belong to genotype Z of avian influenza virus H5N1, now the dominant genotype. H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002, new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks . This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961. Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1 that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997. Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations occurring within this genotype are increasing their pathogenicity. Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.Infected birds transmit H5N1 through their saliva , nasal secretions , feces and blood . Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C (32 °F) (over one month at freezing temperature) or 6 days at 37 °C (99 °F) (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it does not degrade at all. Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry. In October 2004, researchers discovered H5N1 is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading this highly pathogenic strain to chickens , crows , pigeons , and other birds, and the virus was increasing its ability to infect mammals, as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic. "Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability." The New York Times , in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important". On September 29, 2007, researchers reported the H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells. In May 2013, North Korea confirmed a H5N1 bird flu outbreak that forced authorities to kill over 160,000 ducks in Pyongyang . A major outbreak of a new strain of H5N1 in wild birds and poultry appeared in Russia in August 2020 and quickly spread to other parts of Europe by October. Over the winter of 2021 and 2022 avian flu spread among the population of barnacle geese on the Solway Firth, UK, with estimates of up to a third of the Svalbard population being lost; pink-footed geese were also affected there and it seems carried the virus to new sites in northern Scotland. The disease was confirmed in sandwich terns in South Africa in April 2022. In late spring 2022 avian flu outbreaks affected many species of wild bird in the United Kingdom, with heavy losses reported among seabirds returning to breed at colonies in the Northern Isles and Outer Hebrides, including great skuas (bonxie) for which outbreaks had initially been reported in 2021 (Scotland hosts c. 60% of the world's breeding population) – the 2022 census on St Kilda showed a 64% decline on 2019 with 106 dead birds recorded so far (to 6 June), gannets (1000+ birds reported dead at the Shetlands' Hermaness colony alone, where there are around 26,000 breeding pairs), with many more gannets being reported dead at other colonies ( Troup Head , Bass Rock , and St Kilda ); the range of species also seems to be expanding, with reports for many species of wildfowl, seabirds (auks, terns and gulls) and scavenging species (corvids and raptors). Elsewhere in Europe the virus killed hundreds (574+) of Dalmatian pelicans in Greece, and in Israel around 6000 common cranes were found dead at Hula in December 2021. A report by Scientific Task Force on Avian Influenza and Wild Birds on: "H5N1 Highly Pathogenic Avian Influenza in poultry and wild birds: Winter of 2021/2022 with focus on mass mortality of wild birds in UK and Israel" summarises the situation up to 24 January 2022 and mentions that "H5N8 HPAI is still responsible for poultry and wild bird cases mainly in Asia, H5N1 has now in effect replaced this subtype in Africa and Eurasia in both poultry and wild birds". The 2022–2023 season was also the worst recorded outbreak in the United Kingdom, with the British government requiring a so-called "poultry lockdown" which required that farmers keep their birds indoors. Meanwhile, an outbreak of H5N1 on a Spanish mink farm led researchers to believe that they had observed the first case of mammal-to-mammal transmission of H5N1. Human cases were reported in Spain in November 2022, and in the UK in May 2023. By November 2020, large outbreaks of the new strain of H5N1 had started to spread into wild birds and farmed poultry across Asia. In February 2023, human cases were reported in Cambodia. Large losses of poultry and wild birds to H5N1 started to occur in Africa in November 2021 and continued through 2022. Similar to 2021 reports, outbreaks were noted from gannet colonies in Canada, with thousands of birds dead in June 2022, as well as common eiders and great black-backed gulls . Prior to that there were reports of spread in wild birds in over 30 states in the US, including major mortalities in a double-crested cormorant colony in Barrington, Illinois , the virus also spreading to scavengers including three bald eagles in Georgia. Mass die-offs of both birds and mammals were noted in Peru during the 2022–2023 season. In particular, the Peruvian government reported the deaths of approximately 63,000 birds as well as 716 sea lions , with the WHO noting that mammalian spillovers needed to be "monitored closely". In the United States, the 2022–2023 avian outbreak was the worst since H5N1 was first detected. Ecuador entered into a three-month "animal-health emergency" on 29 November 2022, just days after its first case was reported, whereas Argentina and Uruguay both declared "national sanitary emergencies" on 15 February 2023, after their respective first cases were discovered. On 22 May 2023, Brazil, as the world's largest exporter of chicken meat, declared a 180-day emergency following several cases detected in wild birds and created an emergency operations center to plan for and mitigate potential further spread of H5N1. Human cases were reported in Ecuador and Chile. In March 2024, H5N1 infections were recorded for the first time in deceased and sick livestock located in the United States. Goats and cows in three states became ill after exposure to wild birds and culled poultry. In early April, H5N1 was reported to have spread amongst dairy cow herds in multiple states of the USA, indicating cow-to-cow spread. A dairy worker in Texas also became infected, with conjunctivitis being the main symptom. H5N1 was detected in dead birds on the Antarctic mainland for the first time in February 2024. A major outbreak of a new strain of H5N1 in wild birds and poultry appeared in Russia in August 2020 and quickly spread to other parts of Europe by October. Over the winter of 2021 and 2022 avian flu spread among the population of barnacle geese on the Solway Firth, UK, with estimates of up to a third of the Svalbard population being lost; pink-footed geese were also affected there and it seems carried the virus to new sites in northern Scotland. The disease was confirmed in sandwich terns in South Africa in April 2022. In late spring 2022 avian flu outbreaks affected many species of wild bird in the United Kingdom, with heavy losses reported among seabirds returning to breed at colonies in the Northern Isles and Outer Hebrides, including great skuas (bonxie) for which outbreaks had initially been reported in 2021 (Scotland hosts c. 60% of the world's breeding population) – the 2022 census on St Kilda showed a 64% decline on 2019 with 106 dead birds recorded so far (to 6 June), gannets (1000+ birds reported dead at the Shetlands' Hermaness colony alone, where there are around 26,000 breeding pairs), with many more gannets being reported dead at other colonies ( Troup Head , Bass Rock , and St Kilda ); the range of species also seems to be expanding, with reports for many species of wildfowl, seabirds (auks, terns and gulls) and scavenging species (corvids and raptors). Elsewhere in Europe the virus killed hundreds (574+) of Dalmatian pelicans in Greece, and in Israel around 6000 common cranes were found dead at Hula in December 2021. A report by Scientific Task Force on Avian Influenza and Wild Birds on: "H5N1 Highly Pathogenic Avian Influenza in poultry and wild birds: Winter of 2021/2022 with focus on mass mortality of wild birds in UK and Israel" summarises the situation up to 24 January 2022 and mentions that "H5N8 HPAI is still responsible for poultry and wild bird cases mainly in Asia, H5N1 has now in effect replaced this subtype in Africa and Eurasia in both poultry and wild birds". The 2022–2023 season was also the worst recorded outbreak in the United Kingdom, with the British government requiring a so-called "poultry lockdown" which required that farmers keep their birds indoors. Meanwhile, an outbreak of H5N1 on a Spanish mink farm led researchers to believe that they had observed the first case of mammal-to-mammal transmission of H5N1. Human cases were reported in Spain in November 2022, and in the UK in May 2023. By November 2020, large outbreaks of the new strain of H5N1 had started to spread into wild birds and farmed poultry across Asia. In February 2023, human cases were reported in Cambodia. Large losses of poultry and wild birds to H5N1 started to occur in Africa in November 2021 and continued through 2022. Similar to 2021 reports, outbreaks were noted from gannet colonies in Canada, with thousands of birds dead in June 2022, as well as common eiders and great black-backed gulls . Prior to that there were reports of spread in wild birds in over 30 states in the US, including major mortalities in a double-crested cormorant colony in Barrington, Illinois , the virus also spreading to scavengers including three bald eagles in Georgia. Mass die-offs of both birds and mammals were noted in Peru during the 2022–2023 season. In particular, the Peruvian government reported the deaths of approximately 63,000 birds as well as 716 sea lions , with the WHO noting that mammalian spillovers needed to be "monitored closely". In the United States, the 2022–2023 avian outbreak was the worst since H5N1 was first detected. Ecuador entered into a three-month "animal-health emergency" on 29 November 2022, just days after its first case was reported, whereas Argentina and Uruguay both declared "national sanitary emergencies" on 15 February 2023, after their respective first cases were discovered. On 22 May 2023, Brazil, as the world's largest exporter of chicken meat, declared a 180-day emergency following several cases detected in wild birds and created an emergency operations center to plan for and mitigate potential further spread of H5N1. Human cases were reported in Ecuador and Chile. In March 2024, H5N1 infections were recorded for the first time in deceased and sick livestock located in the United States. Goats and cows in three states became ill after exposure to wild birds and culled poultry. In early April, H5N1 was reported to have spread amongst dairy cow herds in multiple states of the USA, indicating cow-to-cow spread. A dairy worker in Texas also became infected, with conjunctivitis being the main symptom. H5N1 was detected in dead birds on the Antarctic mainland for the first time in February 2024. Novel, contagious strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011. Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times. After these 10 passages the H5N1 virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets. After Fouchier offered an article describing this work to the leading academic journal Science , the US National Science Advisory Board for Biosecurity (NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers. However, then the Dutch government declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods. [note 1] After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit for submitting his manuscript, and his research appeared in a special issue of the journal Science devoted to H5N1. The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible. In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute in Harbin , China, had created H5N1 strains which passed between guinea pigs . In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks of creating novel potential pandemic pathogens, culminating in the formation of the Cambridge Working Group , a consensus statement calling for an assessment of the risks and benefits of such research. Although mammals, including humans, had become infected with H5N1 bird flu strains in the past, these cases had ostensibly been caused by direct exposure to infected birds, such as through consumption of birds by wildlife or exposure to infected poultry by farmers. In contrast, the October 2022 mammalian outbreak of H5N1 on a Spanish mink farm showed evidence of being the first recorded case of mammal-to-mammal transmission, with 4 percent of the farm's mink population dying from H5N1-related haemorrhagic pneumonia. The mink respiratory tract is particularly well suited to act as a pathway of viral transmission into humans, which has concerned public health professionals due to the production of all but one approved human vaccine requiring the eggs of chickens, which H5N1 kills at a 90–100 percent fatality rate. Infected mink in Spain were also found to have exhibited the "PB2" viral mutation found when H5N1 jumped into pigs over a decade prior, adding to fears that farms could be acting as incubators and/or reservoirs of the virus, similar to the role of minks in SARS-CoV-2 . As of January 2023, fifteen species of wild and captive mammals had become infected with H5N1 throughout the United States. A mass Caspian seal die-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia's Dagestan republic , worried researchers regarding the possibility that wild mammal-to-mammal spread had begun. A similar mass die-off of 95% of southern elephant seal pups in 2023 also raised concerns of mammal-to-mammal spread, as nursing pups would have had less exposure to birds. In April 2024, spread of H5N1 amongst dairy cow herds in five states of the USA strongly indicated the presence of cow-to-cow transmission. Novel, contagious strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011. Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times. After these 10 passages the H5N1 virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets. After Fouchier offered an article describing this work to the leading academic journal Science , the US National Science Advisory Board for Biosecurity (NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers. However, then the Dutch government declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods. [note 1] After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit for submitting his manuscript, and his research appeared in a special issue of the journal Science devoted to H5N1. The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible. In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute in Harbin , China, had created H5N1 strains which passed between guinea pigs . In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks of creating novel potential pandemic pathogens, culminating in the formation of the Cambridge Working Group , a consensus statement calling for an assessment of the risks and benefits of such research. Although mammals, including humans, had become infected with H5N1 bird flu strains in the past, these cases had ostensibly been caused by direct exposure to infected birds, such as through consumption of birds by wildlife or exposure to infected poultry by farmers. In contrast, the October 2022 mammalian outbreak of H5N1 on a Spanish mink farm showed evidence of being the first recorded case of mammal-to-mammal transmission, with 4 percent of the farm's mink population dying from H5N1-related haemorrhagic pneumonia. The mink respiratory tract is particularly well suited to act as a pathway of viral transmission into humans, which has concerned public health professionals due to the production of all but one approved human vaccine requiring the eggs of chickens, which H5N1 kills at a 90–100 percent fatality rate. Infected mink in Spain were also found to have exhibited the "PB2" viral mutation found when H5N1 jumped into pigs over a decade prior, adding to fears that farms could be acting as incubators and/or reservoirs of the virus, similar to the role of minks in SARS-CoV-2 . As of January 2023, fifteen species of wild and captive mammals had become infected with H5N1 throughout the United States. A mass Caspian seal die-off in December 2022, with 700 infected seals found dead along the Caspian Sea coastline of Russia's Dagestan republic , worried researchers regarding the possibility that wild mammal-to-mammal spread had begun. A similar mass die-off of 95% of southern elephant seal pups in 2023 also raised concerns of mammal-to-mammal spread, as nursing pups would have had less exposure to birds. In April 2024, spread of H5N1 amongst dairy cow herds in five states of the USA strongly indicated the presence of cow-to-cow transmission. As of April 2024, the WHO reported a total of 889 confirmed human cases which resulted in the deaths of 463 people since 2003. [ failed verification ] Following the February 2023 H5N1 death of an 11-year-old girl from Cambodia 's Prey Veng province , her father was confirmed positive for the virus and several close contacts also began showing signs of infection. On 24 February 2023, the WHO expressed concern that the virus had potentially begun to spread among humans and ordered the production of a new human vaccine for H5N1. Following the confirmed infections, the WHO began working with the Cambodian government to determine whether both individuals had gotten the virus directly from infected poultry or if it had indeed been a case of human-to-human transmission. Further sequencing determined that at least one of the two cases was from an older H5N1 clade, 2.3.2.1c, which had circulated as a common H5N1 strain in Cambodia for many years, rather than the more recent clade 2.3.4.4b, which had caused mass poultry deaths since 2020. This older clade had jumped to humans in the past yet hadn't previously resulted in any known human-to-human transmission. On March 1, 2023, as Taiwan raised its travel alert for Cambodia, the WHO and the U.S. CDC, in concert with Cambodian authorities, determined that both of the individuals had been infected through direct contact with poultry. Following the February 2023 H5N1 death of an 11-year-old girl from Cambodia 's Prey Veng province , her father was confirmed positive for the virus and several close contacts also began showing signs of infection. On 24 February 2023, the WHO expressed concern that the virus had potentially begun to spread among humans and ordered the production of a new human vaccine for H5N1. Following the confirmed infections, the WHO began working with the Cambodian government to determine whether both individuals had gotten the virus directly from infected poultry or if it had indeed been a case of human-to-human transmission. Further sequencing determined that at least one of the two cases was from an older H5N1 clade, 2.3.2.1c, which had circulated as a common H5N1 strain in Cambodia for many years, rather than the more recent clade 2.3.4.4b, which had caused mass poultry deaths since 2020. This older clade had jumped to humans in the past yet hadn't previously resulted in any known human-to-human transmission. On March 1, 2023, as Taiwan raised its travel alert for Cambodia, the WHO and the U.S. CDC, in concert with Cambodian authorities, determined that both of the individuals had been infected through direct contact with poultry. Following the February 2023 H5N1 death of an 11-year-old girl from Cambodia 's Prey Veng province , her father was confirmed positive for the virus and several close contacts also began showing signs of infection. On 24 February 2023, the WHO expressed concern that the virus had potentially begun to spread among humans and ordered the production of a new human vaccine for H5N1. Following the confirmed infections, the WHO began working with the Cambodian government to determine whether both individuals had gotten the virus directly from infected poultry or if it had indeed been a case of human-to-human transmission. Further sequencing determined that at least one of the two cases was from an older H5N1 clade, 2.3.2.1c, which had circulated as a common H5N1 strain in Cambodia for many years, rather than the more recent clade 2.3.4.4b, which had caused mass poultry deaths since 2020. This older clade had jumped to humans in the past yet hadn't previously resulted in any known human-to-human transmission. On March 1, 2023, as Taiwan raised its travel alert for Cambodia, the WHO and the U.S. CDC, in concert with Cambodian authorities, determined that both of the individuals had been infected through direct contact with poultry. H5N1 has had a significant effect on human society , especially the financial , political , social , and personal responses to both actual and predicted deaths in birds , humans , and other animals . Billions of dollars are being raised and spent to research H5N1 and prepare for a potential avian influenza pandemic . Over $10 billion have been spent and over 200 million birds have been killed to try to contain H5N1. People have reacted by buying less chicken, causing poultry sales and prices to fall. Many individuals have stockpiled supplies for a possible flu pandemic. International health officials and other experts have pointed out that many unknown questions still hover around the disease. Dr. David Nabarro , Chief Avian Flu Coordinator for the United Nations, and former Chief of Crisis Response for the World Health Organization has described himself as "quite scared" about H5N1's potential impact on humans. Nabarro has been accused of being alarmist before, and on his first day in his role for the United Nations, he proclaimed the avian flu could kill 150 million people. In an interview with the International Herald Tribune , Nabarro compares avian flu to AIDS in Africa, warning that underestimations led to inappropriate focus for research and intervention. In February 2020 an outbreak of H5N1 avian flu occurred in Shuangqing District of Shaoyang City , in the Hunan province . After poultry had become ill from the virus the city killed close to 18,000 chickens to prevent the spread of the illness. Hunan borders Hubei province where Wuhan is located, the epicenter of the coronavirus pandemic .

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Pandemic influenza

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Swine influenza

Swine influenza is an infection caused by any of several types of swine influenza viruses . Swine influenza virus ( SIV ) or swine-origin influenza virus ( S-OIV ) refers to any strain of the influenza family of viruses that is endemic in pigs . As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1 , H1N2 , H2N1, H3N1 , H3N2 , and H2N3 . The swine influenza virus is common throughout pig populations worldwide. Transmission of the virus from pigs to humans is rare and does not always lead to human illness, often resulting only in the production of antibodies in the blood. If transmission causes human illness, it is called a zoonotic swine flu. People with regular exposure to pigs are at increased risk of swine flu infections. Around the mid-20th century, the identification of influenza subtypes was made possible, allowing accurate diagnosis of transmission to humans. Since then, only 50 such transmissions have been confirmed. These strains of swine flu rarely pass from human to human. Symptoms of zoonotic swine flu in humans are similar to those of influenza and influenza-like illness and include chills , fever , sore throat , muscle pains , severe headache , coughing , weakness , shortness of breath, and general discomfort . It is estimated that, in the 2009 flu pandemic , 11–21% of the then global population (of about 6.8 billion), equivalent to around 700 million to 1.4 billion people, contracted the illness—more, in absolute terms, than the Spanish flu pandemic . [ citation needed ] There were 18,449 confirmed fatalities. However, in a 2012 study, the CDC estimated more than 284,000 possible fatalities worldwide, with numbers ranging from 150,000 to 575,000. In August 2010, the World Health Organization declared the swine flu pandemic officially over. Subsequent cases of swine flu were reported in India in 2015, with over 31,156 positive test cases and 1,841 deaths .In pigs, a swine influenza infection produces fever , lethargy , discharge from the nose or eyes, sneezing , coughing , difficulty breathing , eye redness or inflammation, and decreased appetite. In some cases, the infection can cause miscarriage . However, infected pigs may not exhibit any symptoms. Although mortality is usually low (around 1–4%), the virus can cause weight loss and poor growth , in turn causing economic loss to farmers. Infected pigs can lose up to 12 pounds of body weight over a three- to four-week period. Influenza A is responsible for infecting swine and was first identified in 1918. Because both avian and mammalian influenza viruses can bind to receptors in pigs, pigs have often been seen as "mixing vessels", facilitating the evolution of strains that can be passed on to other mammals, such as humans. Direct transmission of a swine flu virus from pigs to humans is possible ( zoonotic swine flu). Fifty cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia , one had Hodgkin's lymphoma , and two were known to be previously healthy. No medical history was reported for the remaining case The true rate of infection may be higher, as most cases only cause a very mild disease and may never be reported or diagnosed. According to the United States Centers for Disease Control and Prevention (CDC), in humans the symptoms of the 2009 "swine flu" H1N1 virus are similar to influenza and influenza-like illness . Symptoms include fever , cough , sore throat , watery eyes, body aches, shortness of breath, headache , weight loss, chills , sneezing, runny nose, coughing, dizziness, abdominal pain, lack of appetite, and fatigue . During the 2009 outbreak, an elevated percentage of patients reporting diarrhea and vomiting . Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms, but also a high likelihood of swine flu due to the person's recent and past medical history. For example, during the 2009 swine flu outbreak in the United States , the CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the seven days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab). The most common cause of death is respiratory failure . Other causes of death are pneumonia (leading to sepsis ), high fever (leading to neurological problems), dehydration (from excessive vomiting and diarrhea ), electrolyte imbalance and kidney failure . Fatalities are more likely in young children and the elderly.Direct transmission of a swine flu virus from pigs to humans is possible ( zoonotic swine flu). Fifty cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia , one had Hodgkin's lymphoma , and two were known to be previously healthy. No medical history was reported for the remaining case The true rate of infection may be higher, as most cases only cause a very mild disease and may never be reported or diagnosed. According to the United States Centers for Disease Control and Prevention (CDC), in humans the symptoms of the 2009 "swine flu" H1N1 virus are similar to influenza and influenza-like illness . Symptoms include fever , cough , sore throat , watery eyes, body aches, shortness of breath, headache , weight loss, chills , sneezing, runny nose, coughing, dizziness, abdominal pain, lack of appetite, and fatigue . During the 2009 outbreak, an elevated percentage of patients reporting diarrhea and vomiting . Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms, but also a high likelihood of swine flu due to the person's recent and past medical history. For example, during the 2009 swine flu outbreak in the United States , the CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the seven days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab). The most common cause of death is respiratory failure . Other causes of death are pneumonia (leading to sepsis ), high fever (leading to neurological problems), dehydration (from excessive vomiting and diarrhea ), electrolyte imbalance and kidney failure . Fatalities are more likely in young children and the elderly.Influenza is common in pigs. About half of breeding pigs in the USA have been exposed to the virus. Antibodies to the virus are also common in pigs in other countries. The main route of transmission is through direct contact between infected and uninfected animals. These close contacts are particularly common during animal transport. Intensive farming may also increase the risk of transmission, as the pigs are raised in very close proximity to each other. Direct transfer of the virus probably occurs though pigs touching noses or through dried mucus. Airborne transmission through the aerosols produced by pigs coughing or sneezing are also an important means of infection. The virus usually spreads quickly through a herd, infecting all the pigs within just a few days. Transmission may also occur through wild animals, such as wild boar , which can spread the disease between farms. People who work with poultry and swine, especially those with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute a population of human hosts in which zoonosis and reassortment can co-occur. Vaccination of these workers against influenza and surveillance for new influenza strains among this population may therefore be an important public health measure. Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study, among others, forms the basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. Other professions at particular risk of infection are veterinarians and meat processing workers, although the risk of infection for both of these groups is lower than that of farm workers. Pigs are unusual because they can be infected with influenza strains that usually infect three different species: pigs, birds, and humans. Within pigs, influenza viruses may exchange genes and produce novel strains. Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. H3N2 evolved from H2N2 by antigenic shift . In August 2004, researchers in China found H5N1 in pigs. These H5N1 infections may be common. In a survey of 10 apparently healthy pigs housed near poultry farms in West Java , where avian flu had broken out, five of the pig samples contained the H5N1 virus. The Indonesian government found similar results in the same region, though additional tests of 150 pigs outside the area were negative. The influenza virion is roughly spherical. It is an enveloped virus; the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are glycoprotein "spikes" of hemagglutinin (HA) and neuraminidase (NA). The combination of HA and NA proteins determine the subtype of influenza virus (A/H1N1, for example). HA and NA are important in the immune response against the virus, and antibodies against these spikes may protect against infection. The antiviral drugs Relenza and Tamiflu target NA by inhibiting neuraminidase and preventing the release of viruses from host cells. Also embedded in the lipid membrane is the M2 protein , which is the target of the antiviral adamantanes amantadine and rimantadine . Of the three genera of influenza viruses that cause human flu , two also cause influenza in pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans are largely distinct, although because of reassortment there have been transfers of genes among strains crossing swine, avian, and human species boundaries. Influenza viruses infect both humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred in the past. For example, influenza C caused small outbreaks of a mild form of influenza amongst children in Japan and California. As a result of the limited host range and lack of genetic diversity in influenza C, this form of influenza does not cause pandemics in humans. Swine influenza is caused by influenza A subtypes H1N1 , H1N2 , H2N3 , H3N1 , and H3N2 . In pigs, four influenza A virus subtypes (H1N1, H1N2, H3N2 and H7N9) are the most common strains worldwide. In the United States , the H1N1 subtype was exclusively prevalent among swine populations before 1998. Since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants , containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. In August 2012, the Center for Disease Control and Prevention confirmed 145 human cases (113 in Indiana, 30 in Ohio, one in Hawaii and one in Illinois) of H3N2v since July 2012. The death of a 61-year-old Madison County, Ohio woman is the first in the USA associated with a new swine flu strain. She contracted the illness after having contact with hogs at the Ross County Fair. Influenza is common in pigs. About half of breeding pigs in the USA have been exposed to the virus. Antibodies to the virus are also common in pigs in other countries. The main route of transmission is through direct contact between infected and uninfected animals. These close contacts are particularly common during animal transport. Intensive farming may also increase the risk of transmission, as the pigs are raised in very close proximity to each other. Direct transfer of the virus probably occurs though pigs touching noses or through dried mucus. Airborne transmission through the aerosols produced by pigs coughing or sneezing are also an important means of infection. The virus usually spreads quickly through a herd, infecting all the pigs within just a few days. Transmission may also occur through wild animals, such as wild boar , which can spread the disease between farms. People who work with poultry and swine, especially those with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute a population of human hosts in which zoonosis and reassortment can co-occur. Vaccination of these workers against influenza and surveillance for new influenza strains among this population may therefore be an important public health measure. Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study, among others, forms the basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. Other professions at particular risk of infection are veterinarians and meat processing workers, although the risk of infection for both of these groups is lower than that of farm workers. Pigs are unusual because they can be infected with influenza strains that usually infect three different species: pigs, birds, and humans. Within pigs, influenza viruses may exchange genes and produce novel strains. Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. H3N2 evolved from H2N2 by antigenic shift . In August 2004, researchers in China found H5N1 in pigs. These H5N1 infections may be common. In a survey of 10 apparently healthy pigs housed near poultry farms in West Java , where avian flu had broken out, five of the pig samples contained the H5N1 virus. The Indonesian government found similar results in the same region, though additional tests of 150 pigs outside the area were negative. Influenza is common in pigs. About half of breeding pigs in the USA have been exposed to the virus. Antibodies to the virus are also common in pigs in other countries. The main route of transmission is through direct contact between infected and uninfected animals. These close contacts are particularly common during animal transport. Intensive farming may also increase the risk of transmission, as the pigs are raised in very close proximity to each other. Direct transfer of the virus probably occurs though pigs touching noses or through dried mucus. Airborne transmission through the aerosols produced by pigs coughing or sneezing are also an important means of infection. The virus usually spreads quickly through a herd, infecting all the pigs within just a few days. Transmission may also occur through wild animals, such as wild boar , which can spread the disease between farms. People who work with poultry and swine, especially those with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute a population of human hosts in which zoonosis and reassortment can co-occur. Vaccination of these workers against influenza and surveillance for new influenza strains among this population may therefore be an important public health measure. Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study, among others, forms the basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. Other professions at particular risk of infection are veterinarians and meat processing workers, although the risk of infection for both of these groups is lower than that of farm workers. Pigs are unusual because they can be infected with influenza strains that usually infect three different species: pigs, birds, and humans. Within pigs, influenza viruses may exchange genes and produce novel strains. Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. H3N2 evolved from H2N2 by antigenic shift . In August 2004, researchers in China found H5N1 in pigs. These H5N1 infections may be common. In a survey of 10 apparently healthy pigs housed near poultry farms in West Java , where avian flu had broken out, five of the pig samples contained the H5N1 virus. The Indonesian government found similar results in the same region, though additional tests of 150 pigs outside the area were negative. The influenza virion is roughly spherical. It is an enveloped virus; the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are glycoprotein "spikes" of hemagglutinin (HA) and neuraminidase (NA). The combination of HA and NA proteins determine the subtype of influenza virus (A/H1N1, for example). HA and NA are important in the immune response against the virus, and antibodies against these spikes may protect against infection. The antiviral drugs Relenza and Tamiflu target NA by inhibiting neuraminidase and preventing the release of viruses from host cells. Also embedded in the lipid membrane is the M2 protein , which is the target of the antiviral adamantanes amantadine and rimantadine . Of the three genera of influenza viruses that cause human flu , two also cause influenza in pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans are largely distinct, although because of reassortment there have been transfers of genes among strains crossing swine, avian, and human species boundaries. Influenza viruses infect both humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred in the past. For example, influenza C caused small outbreaks of a mild form of influenza amongst children in Japan and California. As a result of the limited host range and lack of genetic diversity in influenza C, this form of influenza does not cause pandemics in humans. Swine influenza is caused by influenza A subtypes H1N1 , H1N2 , H2N3 , H3N1 , and H3N2 . In pigs, four influenza A virus subtypes (H1N1, H1N2, H3N2 and H7N9) are the most common strains worldwide. In the United States , the H1N1 subtype was exclusively prevalent among swine populations before 1998. Since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants , containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. In August 2012, the Center for Disease Control and Prevention confirmed 145 human cases (113 in Indiana, 30 in Ohio, one in Hawaii and one in Illinois) of H3N2v since July 2012. The death of a 61-year-old Madison County, Ohio woman is the first in the USA associated with a new swine flu strain. She contracted the illness after having contact with hogs at the Ross County Fair. Of the three genera of influenza viruses that cause human flu , two also cause influenza in pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans are largely distinct, although because of reassortment there have been transfers of genes among strains crossing swine, avian, and human species boundaries.Influenza viruses infect both humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred in the past. For example, influenza C caused small outbreaks of a mild form of influenza amongst children in Japan and California. As a result of the limited host range and lack of genetic diversity in influenza C, this form of influenza does not cause pandemics in humans. Swine influenza is caused by influenza A subtypes H1N1 , H1N2 , H2N3 , H3N1 , and H3N2 . In pigs, four influenza A virus subtypes (H1N1, H1N2, H3N2 and H7N9) are the most common strains worldwide. In the United States , the H1N1 subtype was exclusively prevalent among swine populations before 1998. Since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants , containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. In August 2012, the Center for Disease Control and Prevention confirmed 145 human cases (113 in Indiana, 30 in Ohio, one in Hawaii and one in Illinois) of H3N2v since July 2012. The death of a 61-year-old Madison County, Ohio woman is the first in the USA associated with a new swine flu strain. She contracted the illness after having contact with hogs at the Ross County Fair. The CDC recommends real-time PCR as the method of choice for diagnosing H1N1. The oral or nasal fluid collection and RNA virus-preserving filter-paper card is commercially available. This method allows a specific diagnosis of novel influenza (H1N1) as opposed to seasonal influenza . Near-patient point-of-care tests are in development. Prevention of swine influenza has three components: prevention in pigs, prevention of transmission to humans, and prevention of its spread among humans. Proper handwashing techniques can prevent the virus from spreading. Individuals can prevent infection by not touching the eyes, nose, or mouth, distancing from others who display symptoms of the cold or flu, and avoiding contact with others when displaying symptoms. Methods of preventing the spread of influenza among swine include facility management, herd management, and vaccination ( ATCvet code: QI09AA03 ( WHO ) ). Because much of the illness and death associated with swine flu involves secondary infection by other pathogens, control strategies that rely on vaccination may be insufficient. Control of swine influenza by vaccination has become more difficult in recent decades, as the evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the infection when the virus strains match enough to have significant cross-protection, and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. Present vaccination strategies for SIV control and prevention in swine farms typically include the use of one of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to three commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses. The United States Department of Agriculture researchers say while pig vaccination keeps pigs from getting sick, it does not block infection or shedding of the virus. Facility management includes using disinfectants and ambient temperature to control viruses in the environment. They are unlikely to survive outside living cells for more than two weeks, except in cold (but above freezing) conditions, and are readily inactivated by disinfectants. Herd management includes not adding pigs carrying influenza to herds that have not been exposed to the virus. The virus survives in healthy carrier pigs for up to three months and can be recovered from them between outbreaks. Carrier pigs are usually responsible for the introduction of SIV into previously uninfected herds and countries, so new animals should be quarantined . After an outbreak, as immunity in exposed pigs wanes, new outbreaks of the same strain can occur. Swine can be infected by both avian and human flu strains of influenza, and therefore are hosts where the antigenic shifts can occur that create new influenza strains. The transmission from swine to humans is believed to occur mainly in swine farms, where farmers are in close contact with live pigs. Although strains of swine influenza are usually not able to infect humans, it may occasionally happen, so farmers and veterinarians are encouraged to use face masks when dealing with infected animals. The use of vaccines on swine to prevent their infection is a major method of limiting swine-to-human transmission. Risk factors that may contribute to the swine-to-human transmission include smoking and, especially, not wearing gloves when working with sick animals, thereby increasing the likelihood of subsequent hand-to-eye, hand-to-nose, or hand-to-mouth transmission. Influenza spreads between humans when infected people cough or sneeze, then other people breathe in the virus or touch something with the virus on it and then touch their own face. The CDC warned against touching mucosal membranes such as the eyes, nose, or mouth during the 2009 H1N1 pandemic, as these are common entry points for flu viruses. Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of the illness, although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen, collected during the first five days, for analysis. Recommendations to prevent the spread of the virus among humans include using standard infection control , which includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers , especially after being out in public. Chance of transmission is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution. Influenza can spread in coughs or sneezes, but an increasing body of evidence shows small droplets containing the virus can linger on tabletops, telephones, and other surfaces and be transferred via the fingers to the eyes, nose, or mouth. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms, such as a sudden fever, cough, or muscle aches, should stay away from work or public transportation and should contact a doctor for advice. Social distancing can be another infection control tactic. Individuals should avoid other people who might be infected or if infected themselves isolate from others for the duration of the infection. During active outbreaks, avoiding large gatherings, increasing physical distance in public places, or if possible remaining at home as much as is feasible can prevent further spread of disease. Public health and other responsible authorities have action plans which may request or require social distancing actions, depending on the severity of the outbreak. [ citation needed ] Vaccines are available for different kinds of swine flu. The U.S. Food and Drug Administration (FDA) approved the new swine flu vaccine for use in the United States on September 15, 2009. Studies by the National Institutes of Health show a single dose creates enough antibodies to protect against the virus within about 10 days. In the aftermath of the 2009 pandemic, several studies were conducted to see which population groups were most likely to have received an influenza vaccine. These studies demonstrated that caucasians are much more likely to be vaccinated for seasonal influenza and for the H1N1 strain than African Americans. This could be due to several factors. Historically, there has been mistrust of vaccines and of the medical community from African Americans. [ citation needed ] Many African Americans do not believe vaccines or doctors to be effective. This mistrust stems from the exploitation of the African American communities during studies like the Tuskegee study . Additionally, vaccines are typically administered in clinics, hospitals, or doctor's offices. Many people of lower socioeconomic status are less likely to receive vaccinations because they do not have health insurance. [ citation needed ] Although there is no formal national surveillance system in the United States to determine what viruses are circulating in pigs, an informal surveillance network in the United States is part of a world surveillance network. Methods of preventing the spread of influenza among swine include facility management, herd management, and vaccination ( ATCvet code: QI09AA03 ( WHO ) ). Because much of the illness and death associated with swine flu involves secondary infection by other pathogens, control strategies that rely on vaccination may be insufficient. Control of swine influenza by vaccination has become more difficult in recent decades, as the evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the infection when the virus strains match enough to have significant cross-protection, and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. Present vaccination strategies for SIV control and prevention in swine farms typically include the use of one of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to three commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses. The United States Department of Agriculture researchers say while pig vaccination keeps pigs from getting sick, it does not block infection or shedding of the virus. Facility management includes using disinfectants and ambient temperature to control viruses in the environment. They are unlikely to survive outside living cells for more than two weeks, except in cold (but above freezing) conditions, and are readily inactivated by disinfectants. Herd management includes not adding pigs carrying influenza to herds that have not been exposed to the virus. The virus survives in healthy carrier pigs for up to three months and can be recovered from them between outbreaks. Carrier pigs are usually responsible for the introduction of SIV into previously uninfected herds and countries, so new animals should be quarantined . After an outbreak, as immunity in exposed pigs wanes, new outbreaks of the same strain can occur. Swine can be infected by both avian and human flu strains of influenza, and therefore are hosts where the antigenic shifts can occur that create new influenza strains. The transmission from swine to humans is believed to occur mainly in swine farms, where farmers are in close contact with live pigs. Although strains of swine influenza are usually not able to infect humans, it may occasionally happen, so farmers and veterinarians are encouraged to use face masks when dealing with infected animals. The use of vaccines on swine to prevent their infection is a major method of limiting swine-to-human transmission. Risk factors that may contribute to the swine-to-human transmission include smoking and, especially, not wearing gloves when working with sick animals, thereby increasing the likelihood of subsequent hand-to-eye, hand-to-nose, or hand-to-mouth transmission. Influenza spreads between humans when infected people cough or sneeze, then other people breathe in the virus or touch something with the virus on it and then touch their own face. The CDC warned against touching mucosal membranes such as the eyes, nose, or mouth during the 2009 H1N1 pandemic, as these are common entry points for flu viruses. Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of the illness, although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen, collected during the first five days, for analysis. Recommendations to prevent the spread of the virus among humans include using standard infection control , which includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers , especially after being out in public. Chance of transmission is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution. Influenza can spread in coughs or sneezes, but an increasing body of evidence shows small droplets containing the virus can linger on tabletops, telephones, and other surfaces and be transferred via the fingers to the eyes, nose, or mouth. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms, such as a sudden fever, cough, or muscle aches, should stay away from work or public transportation and should contact a doctor for advice. Social distancing can be another infection control tactic. Individuals should avoid other people who might be infected or if infected themselves isolate from others for the duration of the infection. During active outbreaks, avoiding large gatherings, increasing physical distance in public places, or if possible remaining at home as much as is feasible can prevent further spread of disease. Public health and other responsible authorities have action plans which may request or require social distancing actions, depending on the severity of the outbreak. [ citation needed ] Vaccines are available for different kinds of swine flu. The U.S. Food and Drug Administration (FDA) approved the new swine flu vaccine for use in the United States on September 15, 2009. Studies by the National Institutes of Health show a single dose creates enough antibodies to protect against the virus within about 10 days. In the aftermath of the 2009 pandemic, several studies were conducted to see which population groups were most likely to have received an influenza vaccine. These studies demonstrated that caucasians are much more likely to be vaccinated for seasonal influenza and for the H1N1 strain than African Americans. This could be due to several factors. Historically, there has been mistrust of vaccines and of the medical community from African Americans. [ citation needed ] Many African Americans do not believe vaccines or doctors to be effective. This mistrust stems from the exploitation of the African American communities during studies like the Tuskegee study . Additionally, vaccines are typically administered in clinics, hospitals, or doctor's offices. Many people of lower socioeconomic status are less likely to receive vaccinations because they do not have health insurance. [ citation needed ]Vaccines are available for different kinds of swine flu. The U.S. Food and Drug Administration (FDA) approved the new swine flu vaccine for use in the United States on September 15, 2009. Studies by the National Institutes of Health show a single dose creates enough antibodies to protect against the virus within about 10 days. In the aftermath of the 2009 pandemic, several studies were conducted to see which population groups were most likely to have received an influenza vaccine. These studies demonstrated that caucasians are much more likely to be vaccinated for seasonal influenza and for the H1N1 strain than African Americans. This could be due to several factors. Historically, there has been mistrust of vaccines and of the medical community from African Americans. [ citation needed ] Many African Americans do not believe vaccines or doctors to be effective. This mistrust stems from the exploitation of the African American communities during studies like the Tuskegee study . Additionally, vaccines are typically administered in clinics, hospitals, or doctor's offices. Many people of lower socioeconomic status are less likely to receive vaccinations because they do not have health insurance. [ citation needed ]Although there is no formal national surveillance system in the United States to determine what viruses are circulating in pigs, an informal surveillance network in the United States is part of a world surveillance network. As swine influenza is rarely fatal to pigs, little treatment beyond rest and supportive care is required. Instead, veterinary efforts are focused on preventing the spread of the virus throughout the farm or to other farms. Vaccination and animal management techniques are most important in these efforts. Antibiotics are also used to treat the disease, which, although they have no effect against the influenza virus, do help prevent bacterial pneumonia and other secondary infections in influenza-weakened herds. In Europe the avian-like H1N1 and the human-like H3N2 and H1N2 are the most common influenza subtypes in swine, of which avian-like H1N1 is the most frequent. Since 2009 another subtype, pdmH1N1(2009), emerged globally and also in European pig population. The prevalence varies from country to country but all of the subtypes are continuously circulating in swine herds. In the EU region whole-virus vaccines are available which are inactivated and adjuvanted. Vaccination of sows is common practice and reveals also a benefit to young pigs by prolonging the maternally level of antibodies. Several commercial vaccines are available including a trivalent one being used in sow vaccination and a vaccine against pdmH1N1(2009). In vaccinated sows multiplication of viruses and virus shedding are significantly reduced. [ citation needed ] If a human becomes sick with swine flu, antiviral drugs can make the illness milder and make the patient feel better faster. They may also prevent serious flu complications. For treatment, antiviral drugs work best if started soon after getting sick (within two days of symptoms). Beside antivirals, supportive care at home or in a hospital focuses on controlling fevers, relieving pain and maintaining fluid balance, as well as identifying and treating any secondary infections or other medical problems. The U.S. Centers for Disease Control and Prevention recommends the use of oseltamivir (Tamiflu) or zanamivir (Relenza) for the treatment and/or prevention of infection with swine influenza viruses; however, the majority of people infected with the virus make a full recovery without requiring medical attention or antiviral drugs. The virus isolated in the 2009 outbreak have been found resistant to amantadine and rimantadine . As swine influenza is rarely fatal to pigs, little treatment beyond rest and supportive care is required. Instead, veterinary efforts are focused on preventing the spread of the virus throughout the farm or to other farms. Vaccination and animal management techniques are most important in these efforts. Antibiotics are also used to treat the disease, which, although they have no effect against the influenza virus, do help prevent bacterial pneumonia and other secondary infections in influenza-weakened herds. In Europe the avian-like H1N1 and the human-like H3N2 and H1N2 are the most common influenza subtypes in swine, of which avian-like H1N1 is the most frequent. Since 2009 another subtype, pdmH1N1(2009), emerged globally and also in European pig population. The prevalence varies from country to country but all of the subtypes are continuously circulating in swine herds. In the EU region whole-virus vaccines are available which are inactivated and adjuvanted. Vaccination of sows is common practice and reveals also a benefit to young pigs by prolonging the maternally level of antibodies. Several commercial vaccines are available including a trivalent one being used in sow vaccination and a vaccine against pdmH1N1(2009). In vaccinated sows multiplication of viruses and virus shedding are significantly reduced. [ citation needed ]If a human becomes sick with swine flu, antiviral drugs can make the illness milder and make the patient feel better faster. They may also prevent serious flu complications. For treatment, antiviral drugs work best if started soon after getting sick (within two days of symptoms). Beside antivirals, supportive care at home or in a hospital focuses on controlling fevers, relieving pain and maintaining fluid balance, as well as identifying and treating any secondary infections or other medical problems. The U.S. Centers for Disease Control and Prevention recommends the use of oseltamivir (Tamiflu) or zanamivir (Relenza) for the treatment and/or prevention of infection with swine influenza viruses; however, the majority of people infected with the virus make a full recovery without requiring medical attention or antiviral drugs. The virus isolated in the 2009 outbreak have been found resistant to amantadine and rimantadine . Swine influenza was first proposed to be a disease related to human flu during the 1918 flu pandemic , when pigs became ill at the same time as humans. The first identification of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930. For the following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997 and 2002, new strains of three different subtypes and five different genotypes emerged as causes of influenza among pigs in North America. In 1997–1998, H3N2 strains emerged. These strains, which include genes derived by reassortment from human, swine and avian viruses, have become a major cause of swine influenza in North America. Reassortment between H1N1 and H3N2 produced H1N2 . In 1999 in Canada, a strain of H4N6 crossed the species barrier from birds to pigs, but was contained on a single farm. The H1N1 form of swine flu is one of the descendants of the strain that caused the 1918 flu pandemic . As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans is rare, with only 12 recorded cases in the U.S. since 2005. Nevertheless, the retention of influenza strains in pigs after these strains have disappeared from the human population might make pigs a reservoir where influenza viruses could persist, later emerging to reinfect humans once human immunity to these strains has waned. Swine flu has been reported numerous times as a zoonosis in humans, usually with limited distribution, rarely with a widespread distribution. Outbreaks in swine are common and cause significant economic losses in industry, primarily by causing stunting and extended time to market. For example, this disease costs the British meat industry about £65 million every year. The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs; this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it is not certain in which direction the virus was transferred, some evidence suggests that in this case pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918 after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and other animals including swine suggests the 1918 outbreak in humans followed a reassortment event within a mammal, the exact origin of the 1918 strain remains elusive. It is estimated that anywhere from 50 to 100 million people were killed worldwide. The swine flu was initially seen in the US in April 2009, where the strain of the particular virus was a mixture from 3 types of strains. Six of the genes are very similar to the H1N2 influenza virus that was found in pigs around 2000. On February 5, 1976, a United States army recruit at Fort Dix said he felt tired and weak. He died the next day, and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1) . It was detected only from January 19 to February 9 and did not spread beyond Fort Dix. This new strain appeared to be closely related to the strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) , which spread simultaneously, also caused illness, and persisted until March. Alarmed public health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for the disease. The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began, and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof the vaccine was the cause. According to science writer Patrick Di Justo, however, by the time the truth was known—that the deaths were not proven to be related to the vaccine—it was too late. "The government had long feared mass panic about swine flu—now they feared mass panic about the swine flu vaccinations." This became a strong setback to the program. There were reports of Guillain–Barré syndrome (GBS), a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although whether a link exists is still not clear, this syndrome may be a side effect of influenza vaccines. As a result, Di Justo writes, "the public refused to trust a government-operated health program that killed old people and crippled young people." In total, 48,161,019 Americans, or just over 22% of the population, had been immunized by the time the National Influenza Immunization Program was effectively halted on December 16, 1976. Overall, there were 1098 cases of GBS recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. About one to two cases per 100,000 people of GBS occur every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. Recompensation charges were filed for over 4,000 cases of severe vaccination damage, including 25 deaths, totaling US$3.5 billion, by 1979. The CDC stated most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the New England Journal of Medicine , covering close to 100 million doses of H1N1 flu vaccine, found only 11 cases of GBS, which is lower than the normal rate of the disease in China: "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." In September 1988, a swine flu virus killed one woman and infected others. A 32-year-old woman, Barbara Ann Wieners, was eight months pregnant when she and her husband, Ed, became ill after visiting the hog barn at a county fair in Walworth County, Wisconsin . Barbara died eight days later, after developing pneumonia. The only pathogen identified was an H1N1 strain of swine influenza virus. Doctors were able to induce labor and deliver a healthy daughter before she died. Her husband recovered from his symptoms. Influenza-like illness (ILI) was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since one to three health care personnel who had cared for the pregnant woman developed mild, influenza-like illnesses, and antibody tests suggested they had been infected with swine flu, but there was no community outbreak. In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid strains would later form six out of the eight viral gene segments in the 2009 flu outbreak. On August 20, 2007, Department of Agriculture officers investigated the outbreak of swine flu in Nueva Ecija and central Luzon , Philippines. The mortality rate is less than 10% for swine flu, unless there are complications like hog cholera . On July 27, 2007, the Philippine National Meat Inspection Service (NMIS) raised a hog cholera "red alert" warning over Metro Manila and five regions of Luzon after the disease spread to backyard pig farms in Bulacan and Pampanga , even if they tested negative for the swine flu virus. Since November 2009, 14 deaths as a result of swine flu in Northern Ireland have been reported. The majority of the deceased were reported to have pre-existing health conditions which had lowered their immunity. This closely corresponds to the 19 patients who had died in the year prior due to swine flu, where 18 of the 19 were determined to have lowered immune systems. Because of this, many mothers who have just given birth are strongly encouraged to get a flu shot because their immune systems are vulnerable. Also, studies have shown that people between the ages of 15 and 44 have the highest rate of infection. Although most people now recover, having any conditions that lower one's immune system increases the risk of having the flu become potentially lethal. In Northern Ireland now, approximately 56% of all people under 65 who are entitled to the vaccine have gotten the shot, and the outbreak is said to be under control. Swine flu outbreaks were reported in India in late 2014 and early 2015. As of March 19, 2015 the disease has affected 31,151 people and claimed over 1,841 lives. The largest number of reported cases and deaths due to the disease occurred in the western part of India including states like Delhi , Madhya Pradesh , Rajasthan , and Gujarat Andhra Pradesh Researchers of MIT have claimed that the swine flu has mutated in India to a more virulent version with changes in Hemagglutinin protein, contradicting earlier research by Indian researchers. There was another outbreak in India in 2017. The states of Maharashtra and Gujarat were the worst affected. Gujarat high court has given Gujarat government instructions to control deaths by swine flu. 1,090 people died of swine flu in India in 2019 until August 31, 2019. Swine flu outbreaks were reported in Nepal in the spring of 2015. Up to April 21, 2015, the disease had claimed 26 lives in the most severely affected district, Jajarkot in Northwest Nepal. Cases were also detected in the districts of Kathmandu , Morang , Kaski , and Chitwan . As of 22 April 2015 the Nepal Ministry of Health reported that 2,498 people had been treated in Jajarkot, of whom 552 were believed to have swine flu, and acknowledged that the government's response had been inadequate. The Jajarkot outbreak had just been declared an emergency when the April 2015 Nepal earthquake struck on 25 April 2015, diverting all medical and emergency resources to quake-related rescue and recovery. [ citation needed ] Seven cases of swine flu were reported in Punjab province of Pakistan , mainly in the city of Multan , in January 2017. Cases of swine flu were also reported in Lahore and Faisalabad . As of March 16, 2017, over a hundred confirmed cases of swine flu and at least six deaths were reported in the Maldivian capital of Malé and some other islands. Makeshift flu clinics were opened in Malé. Schools in the capital were closed, prison visitations suspended, several events cancelled, and all non-essential travel to other islands outside the capital was advised against by the HPA. An influenza vaccination program focusing on pregnant women was initiated thereafter. An official visit by Saudi King Salman bin Abdulaziz Al Saud to the Maldives during his Asian tour was also cancelled last minute amidst fears over the outbreak of swine flu. G4 EA H1N1 , also known as the G4 swine flu virus (G4) is a swine influenza virus strain discovered in China. The virus is a variant genotype 4 (G4) Eurasian avian-like (EA) H1N1 virus that mainly affects pigs, but there is some evidence of it infecting people. A peer-reviewed paper from the Proceedings of the National Academy of Sciences ( PNAS ) stated that "G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans ... Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring of swine working populations should be promptly implemented." Michael Ryan, executive director of the World Health Organization (WHO) Health Emergencies Program , stated in July 2020 that this strain of influenza virus was not new and had been under surveillance since 2011. Almost 30,000 swine had been monitored via nasal swabs between 2011 and 2018. While other variants of the virus have appeared and diminished, the study claimed the G4 variant has sharply increased since 2016 to become the predominant strain. The Chinese Ministry of Agriculture and Rural Affairs rebutted the study, saying that the media had interpreted the study "in an exaggerated and nonfactual way" and that the number of pigs sampled was too small to demonstrate G4 had become the dominant strain. Between 2016 and 2018, a serum surveillance program screened 338 swine production workers in China for exposure (presence of antibodies ) to G4 EA H1N1 and found 35 (10.4%) positive. Among another 230 people screened who did not work in the swine industry, 10 (4.4%) were serum positive for antibodies indicating exposure. Two cases of infection caused by the G4 variant have been documented as of July 2020, with no confirmed cases of human-to-human transmission . Health officials (including Anthony Fauci ) say the virus should be monitored, particularly among those in close contact with pigs, but it is not an immediate threat. There are no reported cases or evidence of the virus outside of China as of July 2020. Swine influenza was first proposed to be a disease related to human flu during the 1918 flu pandemic , when pigs became ill at the same time as humans. The first identification of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930. For the following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997 and 2002, new strains of three different subtypes and five different genotypes emerged as causes of influenza among pigs in North America. In 1997–1998, H3N2 strains emerged. These strains, which include genes derived by reassortment from human, swine and avian viruses, have become a major cause of swine influenza in North America. Reassortment between H1N1 and H3N2 produced H1N2 . In 1999 in Canada, a strain of H4N6 crossed the species barrier from birds to pigs, but was contained on a single farm. The H1N1 form of swine flu is one of the descendants of the strain that caused the 1918 flu pandemic . As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans is rare, with only 12 recorded cases in the U.S. since 2005. Nevertheless, the retention of influenza strains in pigs after these strains have disappeared from the human population might make pigs a reservoir where influenza viruses could persist, later emerging to reinfect humans once human immunity to these strains has waned. Swine flu has been reported numerous times as a zoonosis in humans, usually with limited distribution, rarely with a widespread distribution. Outbreaks in swine are common and cause significant economic losses in industry, primarily by causing stunting and extended time to market. For example, this disease costs the British meat industry about £65 million every year. The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs; this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it is not certain in which direction the virus was transferred, some evidence suggests that in this case pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918 after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and other animals including swine suggests the 1918 outbreak in humans followed a reassortment event within a mammal, the exact origin of the 1918 strain remains elusive. It is estimated that anywhere from 50 to 100 million people were killed worldwide. The swine flu was initially seen in the US in April 2009, where the strain of the particular virus was a mixture from 3 types of strains. Six of the genes are very similar to the H1N2 influenza virus that was found in pigs around 2000. The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs; this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it is not certain in which direction the virus was transferred, some evidence suggests that in this case pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918 after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and other animals including swine suggests the 1918 outbreak in humans followed a reassortment event within a mammal, the exact origin of the 1918 strain remains elusive. It is estimated that anywhere from 50 to 100 million people were killed worldwide. The swine flu was initially seen in the US in April 2009, where the strain of the particular virus was a mixture from 3 types of strains. Six of the genes are very similar to the H1N2 influenza virus that was found in pigs around 2000. On February 5, 1976, a United States army recruit at Fort Dix said he felt tired and weak. He died the next day, and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1) . It was detected only from January 19 to February 9 and did not spread beyond Fort Dix. This new strain appeared to be closely related to the strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) , which spread simultaneously, also caused illness, and persisted until March. Alarmed public health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for the disease. The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began, and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof the vaccine was the cause. According to science writer Patrick Di Justo, however, by the time the truth was known—that the deaths were not proven to be related to the vaccine—it was too late. "The government had long feared mass panic about swine flu—now they feared mass panic about the swine flu vaccinations." This became a strong setback to the program. There were reports of Guillain–Barré syndrome (GBS), a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although whether a link exists is still not clear, this syndrome may be a side effect of influenza vaccines. As a result, Di Justo writes, "the public refused to trust a government-operated health program that killed old people and crippled young people." In total, 48,161,019 Americans, or just over 22% of the population, had been immunized by the time the National Influenza Immunization Program was effectively halted on December 16, 1976. Overall, there were 1098 cases of GBS recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. About one to two cases per 100,000 people of GBS occur every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. Recompensation charges were filed for over 4,000 cases of severe vaccination damage, including 25 deaths, totaling US$3.5 billion, by 1979. The CDC stated most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the New England Journal of Medicine , covering close to 100 million doses of H1N1 flu vaccine, found only 11 cases of GBS, which is lower than the normal rate of the disease in China: "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." In September 1988, a swine flu virus killed one woman and infected others. A 32-year-old woman, Barbara Ann Wieners, was eight months pregnant when she and her husband, Ed, became ill after visiting the hog barn at a county fair in Walworth County, Wisconsin . Barbara died eight days later, after developing pneumonia. The only pathogen identified was an H1N1 strain of swine influenza virus. Doctors were able to induce labor and deliver a healthy daughter before she died. Her husband recovered from his symptoms. Influenza-like illness (ILI) was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since one to three health care personnel who had cared for the pregnant woman developed mild, influenza-like illnesses, and antibody tests suggested they had been infected with swine flu, but there was no community outbreak. In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid strains would later form six out of the eight viral gene segments in the 2009 flu outbreak. On August 20, 2007, Department of Agriculture officers investigated the outbreak of swine flu in Nueva Ecija and central Luzon , Philippines. The mortality rate is less than 10% for swine flu, unless there are complications like hog cholera . On July 27, 2007, the Philippine National Meat Inspection Service (NMIS) raised a hog cholera "red alert" warning over Metro Manila and five regions of Luzon after the disease spread to backyard pig farms in Bulacan and Pampanga , even if they tested negative for the swine flu virus. Since November 2009, 14 deaths as a result of swine flu in Northern Ireland have been reported. The majority of the deceased were reported to have pre-existing health conditions which had lowered their immunity. This closely corresponds to the 19 patients who had died in the year prior due to swine flu, where 18 of the 19 were determined to have lowered immune systems. Because of this, many mothers who have just given birth are strongly encouraged to get a flu shot because their immune systems are vulnerable. Also, studies have shown that people between the ages of 15 and 44 have the highest rate of infection. Although most people now recover, having any conditions that lower one's immune system increases the risk of having the flu become potentially lethal. In Northern Ireland now, approximately 56% of all people under 65 who are entitled to the vaccine have gotten the shot, and the outbreak is said to be under control. Swine flu outbreaks were reported in India in late 2014 and early 2015. As of March 19, 2015 the disease has affected 31,151 people and claimed over 1,841 lives. The largest number of reported cases and deaths due to the disease occurred in the western part of India including states like Delhi , Madhya Pradesh , Rajasthan , and Gujarat Andhra Pradesh Researchers of MIT have claimed that the swine flu has mutated in India to a more virulent version with changes in Hemagglutinin protein, contradicting earlier research by Indian researchers. There was another outbreak in India in 2017. The states of Maharashtra and Gujarat were the worst affected. Gujarat high court has given Gujarat government instructions to control deaths by swine flu. 1,090 people died of swine flu in India in 2019 until August 31, 2019. Swine flu outbreaks were reported in Nepal in the spring of 2015. Up to April 21, 2015, the disease had claimed 26 lives in the most severely affected district, Jajarkot in Northwest Nepal. Cases were also detected in the districts of Kathmandu , Morang , Kaski , and Chitwan . As of 22 April 2015 the Nepal Ministry of Health reported that 2,498 people had been treated in Jajarkot, of whom 552 were believed to have swine flu, and acknowledged that the government's response had been inadequate. The Jajarkot outbreak had just been declared an emergency when the April 2015 Nepal earthquake struck on 25 April 2015, diverting all medical and emergency resources to quake-related rescue and recovery. [ citation needed ] Seven cases of swine flu were reported in Punjab province of Pakistan , mainly in the city of Multan , in January 2017. Cases of swine flu were also reported in Lahore and Faisalabad . As of March 16, 2017, over a hundred confirmed cases of swine flu and at least six deaths were reported in the Maldivian capital of Malé and some other islands. Makeshift flu clinics were opened in Malé. Schools in the capital were closed, prison visitations suspended, several events cancelled, and all non-essential travel to other islands outside the capital was advised against by the HPA. An influenza vaccination program focusing on pregnant women was initiated thereafter. An official visit by Saudi King Salman bin Abdulaziz Al Saud to the Maldives during his Asian tour was also cancelled last minute amidst fears over the outbreak of swine flu.On February 5, 1976, a United States army recruit at Fort Dix said he felt tired and weak. He died the next day, and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1) . It was detected only from January 19 to February 9 and did not spread beyond Fort Dix. This new strain appeared to be closely related to the strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) , which spread simultaneously, also caused illness, and persisted until March. Alarmed public health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for the disease. The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began, and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof the vaccine was the cause. According to science writer Patrick Di Justo, however, by the time the truth was known—that the deaths were not proven to be related to the vaccine—it was too late. "The government had long feared mass panic about swine flu—now they feared mass panic about the swine flu vaccinations." This became a strong setback to the program. There were reports of Guillain–Barré syndrome (GBS), a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although whether a link exists is still not clear, this syndrome may be a side effect of influenza vaccines. As a result, Di Justo writes, "the public refused to trust a government-operated health program that killed old people and crippled young people." In total, 48,161,019 Americans, or just over 22% of the population, had been immunized by the time the National Influenza Immunization Program was effectively halted on December 16, 1976. Overall, there were 1098 cases of GBS recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. About one to two cases per 100,000 people of GBS occur every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. Recompensation charges were filed for over 4,000 cases of severe vaccination damage, including 25 deaths, totaling US$3.5 billion, by 1979. The CDC stated most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the New England Journal of Medicine , covering close to 100 million doses of H1N1 flu vaccine, found only 11 cases of GBS, which is lower than the normal rate of the disease in China: "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." In September 1988, a swine flu virus killed one woman and infected others. A 32-year-old woman, Barbara Ann Wieners, was eight months pregnant when she and her husband, Ed, became ill after visiting the hog barn at a county fair in Walworth County, Wisconsin . Barbara died eight days later, after developing pneumonia. The only pathogen identified was an H1N1 strain of swine influenza virus. Doctors were able to induce labor and deliver a healthy daughter before she died. Her husband recovered from his symptoms. Influenza-like illness (ILI) was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since one to three health care personnel who had cared for the pregnant woman developed mild, influenza-like illnesses, and antibody tests suggested they had been infected with swine flu, but there was no community outbreak. In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid strains would later form six out of the eight viral gene segments in the 2009 flu outbreak. On August 20, 2007, Department of Agriculture officers investigated the outbreak of swine flu in Nueva Ecija and central Luzon , Philippines. The mortality rate is less than 10% for swine flu, unless there are complications like hog cholera . On July 27, 2007, the Philippine National Meat Inspection Service (NMIS) raised a hog cholera "red alert" warning over Metro Manila and five regions of Luzon after the disease spread to backyard pig farms in Bulacan and Pampanga , even if they tested negative for the swine flu virus. Since November 2009, 14 deaths as a result of swine flu in Northern Ireland have been reported. The majority of the deceased were reported to have pre-existing health conditions which had lowered their immunity. This closely corresponds to the 19 patients who had died in the year prior due to swine flu, where 18 of the 19 were determined to have lowered immune systems. Because of this, many mothers who have just given birth are strongly encouraged to get a flu shot because their immune systems are vulnerable. Also, studies have shown that people between the ages of 15 and 44 have the highest rate of infection. Although most people now recover, having any conditions that lower one's immune system increases the risk of having the flu become potentially lethal. In Northern Ireland now, approximately 56% of all people under 65 who are entitled to the vaccine have gotten the shot, and the outbreak is said to be under control. Swine flu outbreaks were reported in India in late 2014 and early 2015. As of March 19, 2015 the disease has affected 31,151 people and claimed over 1,841 lives. The largest number of reported cases and deaths due to the disease occurred in the western part of India including states like Delhi , Madhya Pradesh , Rajasthan , and Gujarat Andhra Pradesh Researchers of MIT have claimed that the swine flu has mutated in India to a more virulent version with changes in Hemagglutinin protein, contradicting earlier research by Indian researchers. There was another outbreak in India in 2017. The states of Maharashtra and Gujarat were the worst affected. Gujarat high court has given Gujarat government instructions to control deaths by swine flu. 1,090 people died of swine flu in India in 2019 until August 31, 2019. Swine flu outbreaks were reported in Nepal in the spring of 2015. Up to April 21, 2015, the disease had claimed 26 lives in the most severely affected district, Jajarkot in Northwest Nepal. Cases were also detected in the districts of Kathmandu , Morang , Kaski , and Chitwan . As of 22 April 2015 the Nepal Ministry of Health reported that 2,498 people had been treated in Jajarkot, of whom 552 were believed to have swine flu, and acknowledged that the government's response had been inadequate. The Jajarkot outbreak had just been declared an emergency when the April 2015 Nepal earthquake struck on 25 April 2015, diverting all medical and emergency resources to quake-related rescue and recovery. [ citation needed ]Seven cases of swine flu were reported in Punjab province of Pakistan , mainly in the city of Multan , in January 2017. Cases of swine flu were also reported in Lahore and Faisalabad . As of March 16, 2017, over a hundred confirmed cases of swine flu and at least six deaths were reported in the Maldivian capital of Malé and some other islands. Makeshift flu clinics were opened in Malé. Schools in the capital were closed, prison visitations suspended, several events cancelled, and all non-essential travel to other islands outside the capital was advised against by the HPA. An influenza vaccination program focusing on pregnant women was initiated thereafter. An official visit by Saudi King Salman bin Abdulaziz Al Saud to the Maldives during his Asian tour was also cancelled last minute amidst fears over the outbreak of swine flu.G4 EA H1N1 , also known as the G4 swine flu virus (G4) is a swine influenza virus strain discovered in China. The virus is a variant genotype 4 (G4) Eurasian avian-like (EA) H1N1 virus that mainly affects pigs, but there is some evidence of it infecting people. A peer-reviewed paper from the Proceedings of the National Academy of Sciences ( PNAS ) stated that "G4 EA H1N1 viruses possess all the essential hallmarks of being highly adapted to infect humans ... Controlling the prevailing G4 EA H1N1 viruses in pigs and close monitoring of swine working populations should be promptly implemented." Michael Ryan, executive director of the World Health Organization (WHO) Health Emergencies Program , stated in July 2020 that this strain of influenza virus was not new and had been under surveillance since 2011. Almost 30,000 swine had been monitored via nasal swabs between 2011 and 2018. While other variants of the virus have appeared and diminished, the study claimed the G4 variant has sharply increased since 2016 to become the predominant strain. The Chinese Ministry of Agriculture and Rural Affairs rebutted the study, saying that the media had interpreted the study "in an exaggerated and nonfactual way" and that the number of pigs sampled was too small to demonstrate G4 had become the dominant strain. Between 2016 and 2018, a serum surveillance program screened 338 swine production workers in China for exposure (presence of antibodies ) to G4 EA H1N1 and found 35 (10.4%) positive. Among another 230 people screened who did not work in the swine industry, 10 (4.4%) were serum positive for antibodies indicating exposure. Two cases of infection caused by the G4 variant have been documented as of July 2020, with no confirmed cases of human-to-human transmission . Health officials (including Anthony Fauci ) say the virus should be monitored, particularly among those in close contact with pigs, but it is not an immediate threat. There are no reported cases or evidence of the virus outside of China as of July 2020.

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Pandemic influenza

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Influenza B virus

Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae . Influenza B virus is only known to infect certain mammal species, including humans , ferrets , pigs , and seals . This limited host range is apparently responsible for the lack of influenza pandemics associated with influenza B virus, in contrast with those caused by the morphologically similar influenza A virus , as both mutate by both antigenic drift and reassortment . Nevertheless, it is accepted that influenza B virus could cause significant morbidity and mortality worldwide, and significantly impacts adolescents and schoolchildren. There are two known circulating lineages of influenza B virus based on the antigenic properties of the surface glycoprotein hemagglutinin . The lineages are termed B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. The quadrivalent influenza vaccine licensed by the CDC has been designed to protect against both co-circulating lineages and as of 2016 has been shown to have greater effectiveness in prevention of influenza caused by influenza B virus than the previous trivalent vaccine. However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures. In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. For the 2024–2025 Northern Hemisphere influenza season, the US Food and Drug Administration (FDA) recommends removing B/Yamagata from all influenza vaccines. The European Medicines Agency (EMA) recommends removing B/Yamagata from influenza vaccines for the 2024–2025 seasonal flu vaccine composition. The influenza B virus capsid is enveloped while its virion consists of an envelope, a matrix protein, a nucleoprotein complex, a nucleocapsid , and a polymerase complex. It is sometimes spherical and sometimes filamentous. Its 500 or so surface projections are made of hemagglutinin and neuraminidase . The influenza B virus genome is 14,548 nucleotides long and consists of eight segments of linear negative-sense, single-stranded RNA . The multipartite genome is encapsidated , each segment in a separate nucleocapsid, and the nucleocapsids are surrounded by one envelope . The ancestor of influenza viruses A and B and the ancestor of influenza virus C are estimated to have diverged from a common ancestor around 8,000 years ago. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the subtypes of influenza A virus are estimated to have diverged 2,000 years ago. Metatranscriptomics studies have also identified closely related "influenza B-like" viruses such as the Wuhan spiny eel influenza virus and also "influenza B-like" viruses in a number of vertebrate species such as salamanders and fish. Diminishing the impact of this virus is the fact that, "in humans, influenza B viruses evolve slower than A viruses and faster than C viruses". Influenza B virus mutates at a rate 2 to 3 times slower than type A. In 1936, Thomas Francis Jr. discovered the ferret influenza B virus. Also in 1936, Macfarlane Burnet made the discovery that influenza virus may be cultured in hen embryonated eggs. This prompted research into the properties of the virus and the creation and application of inactivated vaccines in the late 1930s and early 1940s. Inactivated vaccines' usefulness as a preventative measure was proven in the 1950s. Later, 2003 saw the approval of the first live, attenuated influenza vaccine. Looking into influenza B specifically, Thomas Francis Jr. isolated influenza B virus in 1936. However, it was not until 1940 that influenza B viruses were discovered. In 1942, a new bivalent vaccine was developed that protected against both the H1N1 strain of influenza A and the newly discovered influenza B virus. In today's current world, even while some technology has advanced and flu vaccines now cover both strains of influenza A and B, the science is still based on findings from almost a century ago. The viruses included in flu vaccines are changed each year to match the strains of flu that are most likely to make people sick that year since flu viruses can develop swiftly and new mutations have appeared each year, like H1N1. Even though there have been two different lineages of influenza B viruses that were circulating during most seasons, flu vaccinations were long meant to protect against three different flu viruses: the influenza A(H1N1), influenza A( H3N2 ), and one type of influenza B virus. The second lineage of the B virus was since added to provide greater defense against circulating flu viruses. Two influenza A viruses and two influenza B viruses have up until 2023 been among the four flu viruses that a quadrivalent vaccine was intended to protect against. As of 2022 all flu vaccines in the United States were quadrivalent. The four main types of type A and B influenza viruses that are most likely to spread and make people sick during the upcoming flu season have been the targets of seasonal influenza (flu) vaccines. All of the available flu vaccinations in the United States have offered protection against the influenza A(H1), A(H3), B/Yamagata, and B/Victoria lineage viruses. Each of these four vaccine virus components has been chosen based on which flu viruses are infecting people ahead of the upcoming flu season, how widely they are spreading, how well the vaccines from the previous flu season may protect against those flu viruses, and the vaccine viruses' capacity to offer cross-protection. For the 2022–2023 flu season, there were three flu vaccines that were preferentially recommended for people 65 years and older; various influenza (flu) vaccinations are authorized for use in people of various age groups. In March 2022, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) convened in Silver Spring, Maryland, to choose the influenza viruses that would make up the influenza vaccine for the 2022–2023 influenza season in the United States. The committee proposed using A(H1N1)pdm09 , A(H3N2), and B/Austria/1359417/2021-like viruses for trivalent influenza vaccines to be utilized in the U.S. However, the B/Yamagata lineage might have become extinct in 2020/2021 due to COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. In October 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. In 1940, an acute respiratory illness outbreak in Northern America led to the discovery of influenza B virus (IBV), which was later discovered to not have any antigenic cross-reactivity with influenza A virus (IAV). Based on calculations of the rate of amino acid substitutions in HA proteins, it was estimated that IBV and IAV diverged from one another around 4000 years ago. However, the mechanisms of replication and transcription, as well as the functionality of the majority of viral proteins, appear to be largely conserved, with some unusual differences. Although IBV has occasionally been found in seals and pigs, its primary host species is the human. IBVs can also spread epidemics throughout the world, but they receive less attention than IAVs do due to their less prevalent nature, both in infecting hosts and in the symptoms that result from infection. IBVs used to be unclassified, but since the 1980s, they have been divided into the B/Yamagata and B/Victoria lineages. IBVs have further divisions known as clades and sub-clades, just like IAVs do. Hemagglutinin (HA) and neuraminidase (NA) are two virus surface antigens that are constantly changing. Antigenic drift or antigenic shift are two possible influenza viral changes. Small changes in the HA and NA of influenza viruses caused by antigenic drift result in the creation of novel strains that the immune system of humans might not be able to identify. These emerging strains are the influenza virus's evolutionary responses to a potent immunological response across the population. The main cause of influenza recurrence is antigenic drift, which makes it essential to reevaluate and update the influenza vaccine's ingredient list every year. Annual influenza outbreaks are caused by antigenic drift and declining immunity, when the residual defenses from prior exposures to related viruses are incomplete. Antigenic drift occurs in influenza A, B, and C. Hemagglutination inhibition experiments using ferret serum after infection allowed the identification of two very different antigenic influenza type B variants in the years 1988–1989. These viruses shared antigens with either B/Yamagata/16/88, a variation that was discovered in Japan in May 1988, or B/Victoria/2/87, the most recent reference strain. The B/Victoria/2/87 virus shared antigens with all influenza B viruses discovered in the United States during an outbreak in the winter of 1988–1989. In Japan, influenza B virus reinfection was investigated virologically in 1985–1991 and epidemiologically in 1979–1991 in children. Four influenza B virus outbreaks that each included antigenic drift occurred during the course of this study. Between the epidemics in 1987–1988 and 1989–1990, there was a significant genetic and antigenic change in the viruses. Depending on the influenza seasons, the minimum rate of reinfection with influenza B virus for the entire period was between 2 and 25%. Hemagglutination inhibition assays were used to examine the antigens of the influenza B virus primary and reinfection strains that were isolated from 18 children between the years of 1985 and 1990, which encompassed three epidemic periods. The findings revealed that reinfection occurred with the viruses recovered during the 1984–1985 and 1987–1988 influenza seasons, which belonged to the same lineage and were antigenically close. Today, the B/Yamagata lineage might be extinct as a result of COVID-19 pandemic measures, and there have been no naturally occurring cases confirmed since March 2020. Although this development has resulted in updated recommendations regarding vaccine composition, continued surveillance is required to assess this conclusion fully, as pauses in IBV circulation have been observed before.

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Pandemic influenza

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Avian influenza

Avian influenza , also known as avian flu , is a bird flu caused by the influenza A virus , which can infect people. [note 1] It is similar to other types of animal flu in that it is caused by a virus strain that has adapted to a specific host . The type with the greatest risk is highly pathogenic avian influenza (HPAI). Though influenza A is adapted to birds, it can also stably adapt and sustain person-to-person transmission. Recent influenza research into the genes of the Spanish flu virus shows it to have genes adapted from both human and avian strains. Pigs can also be infected with human, avian, and swine influenza viruses, allowing for mixtures of genes ( reassortment ) to create a new virus, which can cause an antigenic shift to a new influenza A virus subtype which most people have little to no immune protection against. Avian influenza strains are divided into two types based on their pathogenicity : high pathogenicity (HP) or low pathogenicity (LP). The most well-known HPAI strain, H5N1 , was first isolated from a farmed goose in Guangdong Province, China in 1996, and also has low pathogenic strains found in North America. Companion birds in captivity are unlikely to contract the virus and there has been no report of a companion bird with avian influenza since 2003. Pigeons can contract avian strains, but rarely become ill and are incapable of transmitting the virus efficiently to humans or other animals. The type of influenza known informally as avian or bird flu is caused by viruses adapted to birds . The most widely quoted date for the beginning of recorded history of avian influenza (initially known as fowl plague) was in 1878 when it was differentiated from other diseases that caused high mortality rates in birds. Fowl plague or Avian Flu also included Newcastle disease until as recently as the 1950s. Between 1959 and 1995, there were 15 recorded occasions of the emergence of HPAI viruses in poultry, but losses were minimal. Between 1996 and 2008, HPAI outbreaks in poultry have occurred at least 11 times and 4 of these outbreaks have involved millions of birds. In the 1990s, the world's poultry population grew 76% in developing countries and 23% in developed countries, contributing to the increased prevalence of avian influenza. Before the 1990s, HPAI caused high mortality in poultry, but infections were sporadic and contained. Outbreaks have become more common due to the high density and frequent movement of flocks from intensive poultry production. [ citation needed ] Influenza A/ H5N1 was first isolated from a goose in China in 1996. Human infections were first reported in 1997 in Hong Kong. Since 2003, more than 700 human cases of Asian HPAI H5N1 have been reported to the WHO , primarily from 15 countries in Asia, Africa, the Pacific, Europe, and the Middle East, though over 60 countries have been affected. Between early 2013 and early 2017, 916 lab-confirmed human cases of H7N9 were reported to the World Health Organization (WHO). On 9 January 2017, the National Health and Family Planning Commission of China reported to the WHO 106 cases of H7N9 which occurred from late November through late December, including 35 deaths, 2 potential cases of human-to-human transmission, and 80 of these 106 persons stating that they have visited live poultry markets. The cases are reported from Jiangsu (52), Zhejiang (21), Anhui (14), Guangdong (14), Shanghai (2), Fujian (2) and Hunan (1). Similar sudden increases in the number of human cases of H7N9 have occurred in previous years during December and January. From 2014 through 2015, United States poultry and egg producers experienced the largest outbreak of H5N2 in recorded history with approximately 51 million birds depopulated to control the spread of the disease. From May to June 2015, 25 million birds were culled, equating to 409,836 birds per day, or 284 birds per minute. In total, the 2014-2015 H5N2/H5N8 outbreak cost US$879 million in public expenditures and the United States egg and poultry industry more than US$3 billion to eradicate the disease from poultry production. This was the most costly United States HPAI outbreak to date. By the end of 2020, several outbreaks of various bird flus were reported in Europe. Since mid-October several European countries, including Belgium, Denmark, France, Germany, Ireland, the Netherlands, Sweden, and the United Kingdom have reported outbreaks of highly pathogenic avian influenza (HPAI) viruses, mostly in wild birds. Positive tests were also among poultry and captive birds. According to a report by the European Centre for Disease Prevention and Control (ECDC), three varieties of HPAI viruses were found, A(H5N8), A(H5N5) and A(H5N1), with H5N8 being the most commonly found. In Germany, 29,000 chickens were killed to halt the spread of H5N8. In Belgium, H5N5 was found on a poultry farm according to the World Organization for Animal Health (OIE). The outbreak was reported in Menen, near the border with France, and killed 600 birds and the culling of an additional 151,000 chickens from the flock. Since early 2022, more than 58 million birds in 47 states have died either directly from a bird flu virus infection or been culled (killed) as a result of possible exposure to infected birds. The recent strain has cost the government $661 million with no end to the outbreak in sight despite severe mitigation measures put in place by the industry after the 2015 outbreak. Iowa, the biggest egg producer in the United States, has been the most affected, with almost 16 million birds slaughtered. In January 2023, in Tijuana , a dozen eggs were priced at about $2.30, yet $7.37 in California , and border crossers who declare the eggs at the inspection stations are told the items aren't allowed and must be turned over. In March 2023 Senegal reported an outbreak of the disease on a poultry farm in the village of Potou near the northwestern town of Louga. The disease has killed 500 birds at the farm in Potou, while 1,229 bird deaths have been recorded at the Langue de Barbarie Park and surrounding areas. A week later, in Gambia authorities detected H5N1 bird flu on a wild bird reserve. During September and October 2023 South Africa reported one of its worst outbreaks of bird flu. Millions of chickens were killed over the first few weeks and supplies of poultry meat were threatened and supermarkets across the country were short of eggs. From 2014 through 2015, United States poultry and egg producers experienced the largest outbreak of H5N2 in recorded history with approximately 51 million birds depopulated to control the spread of the disease. From May to June 2015, 25 million birds were culled, equating to 409,836 birds per day, or 284 birds per minute. In total, the 2014-2015 H5N2/H5N8 outbreak cost US$879 million in public expenditures and the United States egg and poultry industry more than US$3 billion to eradicate the disease from poultry production. This was the most costly United States HPAI outbreak to date. By the end of 2020, several outbreaks of various bird flus were reported in Europe. Since mid-October several European countries, including Belgium, Denmark, France, Germany, Ireland, the Netherlands, Sweden, and the United Kingdom have reported outbreaks of highly pathogenic avian influenza (HPAI) viruses, mostly in wild birds. Positive tests were also among poultry and captive birds. According to a report by the European Centre for Disease Prevention and Control (ECDC), three varieties of HPAI viruses were found, A(H5N8), A(H5N5) and A(H5N1), with H5N8 being the most commonly found. In Germany, 29,000 chickens were killed to halt the spread of H5N8. In Belgium, H5N5 was found on a poultry farm according to the World Organization for Animal Health (OIE). The outbreak was reported in Menen, near the border with France, and killed 600 birds and the culling of an additional 151,000 chickens from the flock. Since early 2022, more than 58 million birds in 47 states have died either directly from a bird flu virus infection or been culled (killed) as a result of possible exposure to infected birds. The recent strain has cost the government $661 million with no end to the outbreak in sight despite severe mitigation measures put in place by the industry after the 2015 outbreak. Iowa, the biggest egg producer in the United States, has been the most affected, with almost 16 million birds slaughtered. In January 2023, in Tijuana , a dozen eggs were priced at about $2.30, yet $7.37 in California , and border crossers who declare the eggs at the inspection stations are told the items aren't allowed and must be turned over. In March 2023 Senegal reported an outbreak of the disease on a poultry farm in the village of Potou near the northwestern town of Louga. The disease has killed 500 birds at the farm in Potou, while 1,229 bird deaths have been recorded at the Langue de Barbarie Park and surrounding areas. A week later, in Gambia authorities detected H5N1 bird flu on a wild bird reserve. During September and October 2023 South Africa reported one of its worst outbreaks of bird flu. Millions of chickens were killed over the first few weeks and supplies of poultry meat were threatened and supermarkets across the country were short of eggs. Genetic factors in distinguishing between " human flu viruses" and "avian flu viruses" include: The evolution of avian influenza virus has been influenced by genetic variation in the virus population due to genome segment reassortment and mutation . Also homologous recombination occurs in viral genes , suggesting that genetic variation generated by homologous recombination has also played a role in driving the evolution of the virus and potentially has affected virulence and host range. Out of the three types of influenza viruses ( A , B , and C ), influenza A virus can cause zoonotic infections, with a natural reservoir almost entirely in birds. There are many subtypes of avian influenza viruses, but only some strains of five subtypes have been known to infect humans: H5N1, H7N3, H7N7, H7N9, and H9N2. At least one person, an elderly woman in Jiangxi Province , China, died of pneumonia in December 2013 from the H10N8 strain. She was the first human fatality confirmed to be caused by that strain. Most human cases of the avian flu are a result of either handling dead infected birds or from contact with infected fluids. It can also be spread through contaminated surfaces and droppings. While most wild birds have only a mild form of the H5N1 strain, once domesticated birds such as chickens or turkeys are infected, H5N1 can potentially become much more deadly because the birds are often in close contact. H5N1 is a large threat in Asia with infected poultry due to low hygiene conditions and close quarters. Although it is easy for humans to contract the infection from birds, human-to-human transmission is more difficult without prolonged contact. Public health officials believe strains of avian flu may mutate to become easily transmissible between humans. Spreading of H5N1 from Asia to Europe is much more likely caused by both legal and illegal poultry trades than dispersing through wild bird migrations, being that in recent studies, there were no secondary rises in infection in Asia when wild birds migrate south again from their breeding grounds. Instead, the infection patterns followed transportation such as railroads, roads, and country borders, suggesting poultry trade as being much more likely. While there have been strains of avian flu to exist in the United States, they have been extinguished and have not been known to infect humans. [ citation needed ] Examples of avian influenza A virus strains: Avian influenza is most often spread by contact between infected and healthy birds, though can also be spread indirectly through contaminated equipment. The virus is found in secretions from the nostrils, mouth, and eyes of infected birds as well as their droppings. HPAI infection is spread to people often through direct contact with infected poultry, such as during slaughter or plucking. Though the virus can spread through airborne secretions, the disease itself is not an airborne disease. Highly pathogenic strains spread quickly among flocks and can destroy a flock within 28 hours; the less pathogenic strains may affect egg production but are much less deadly. [ citation needed ] Although it is possible for humans to contract the avian influenza virus from birds, human-to-human transmission is much more difficult without prolonged contact. Public health officials believe strains of avian flu may mutate to become easily transmissible between humans. Some strains of avian influenza are present in the intestinal tract of large numbers of shore birds and water birds, but these strains rarely cause human infection. Five manmade ecosystems have contributed to modern avian influenza virus ecology: integrated indoor commercial poultry, range-raised commercial poultry, live poultry markets, backyard and hobby flocks, and bird collection and trading systems including cockfighting . Indoor commercial poultry has had the largest impact on the spread of HPAI, with the increase in HPAI outbreaks largely the result of increased commercial production since the 1990s. In the early days of the HPAI H5N1 pandemic, village poultry and their owners were frequently implicated in disease transmission. Village poultry, also known as backyard and hobby flocks, are small flocks raised under extensive conditions and often allowed free range between multiple households. Further research suggested these flocks pose less of a threat than intensively raised commercial poultry with homogenous genetic stock and poor biosecurity . Backyard and village poultry also do not travel great distances compared to transport of intensively raised poultry and contribute less to the spread of HPAI. The highly pathogenic influenza A virus subtype H5N1 is an emerging avian influenza virus that is causing global concern as a potential pandemic threat. It is often referred to simply as "bird flu" or "avian influenza", even though it is only one of many subtypes. H5N1 has killed millions of poultry in a growing number of countries throughout Asia, Europe, and Africa. Health experts are concerned that the coexistence of human flu viruses and avian flu viruses (especially H5N1) will provide an opportunity for genetic material to be exchanged between species-specific viruses, possibly creating a new virulent influenza strain that is easily transmissible and lethal to humans. The mortality rate for humans with H5N1 is 60%. Since the first human H5N1 outbreak occurred in 1997, there has been an increasing number of HPAI H5N1 bird-to-human transmissions, leading to clinically severe and fatal human infections. Because a significant species barrier exists between birds and humans, the virus does not easily spread to humans. Some cases of infection were researched to discern whether human-to-human transmission occurred. More research is necessary to understand the pathogenesis and epidemiology of the H5N1 virus in humans. Exposure routes and other disease transmission characteristics, such as genetic and immunological factors that may increase the likelihood of infection, are not clearly understood. The first known transmission of H5N1 to a human occurred in Hong Kong in 1997, when there was an outbreak of 18 human cases; 6 deaths were confirmed. None of the infected people worked with poultry. After culling all of the poultry in the area, no more cases were diagnosed. In 2006, the first human-to-human transmission likely occurred when seven members of a family in Sumatra became infected after contact with a family member who had worked with infected poultry. Although millions of birds have become infected with the virus since its discovery, 359 people have died from H5N1 in twelve countries according to World Health Organization reports as of August 10, 2012. The H5N1 outbreak in Thailand caused massive economic losses, especially among poultry workers. Infected birds were culled and slaughtered. The public lost confidence with the poultry products, thus decreasing the consumption of chicken products. This also elicited a ban from importing countries. Several factors enhanced the virality, including bird migration, cool temperature (increases virus survival) and several festivals at that time. A mutation in the virus was discovered in two Guangdong patients in February 2017 which rendered it more deadly to chickens, inasmuch as it could infect every organ; the risk to humans was not increased. A study published in 2012 in Science Magazine reported on research findings that allowed for the airborne transmission of H5N1 in laboratory ferrets. The study in question created airborne H5N1 via amino acid substitutions that largely mitigated the devastating effects of the disease. This fact was underscored by the 0% fatality rate among the ferrets infected via airborne transmission, as well as the fundamental biology underlying the substitutions. Flu viruses attach to host cells via the hemagluttinin proteins on their envelope. These hemagluttinin proteins bind to sialic acid receptors on host cells, which can fall into two categories. The sialic acid receptors can be either 2,3 or 2,6-linked, with the species of origin largely deciding receptor preference. In influenzas of avian origin 2,3-linkage is preferred, vs. influenzas of human origin in which 2,6-linkage is preferable. 2,3-linked SA receptors in humans are found predominantly in the lower respiratory tract, a fact that is the primary foundation for the deadliness of avian influenzas in humans, and also the key to their lack of airborne transmission. In the study that created an airborne avian influenza among ferrets it was necessary to switch the receptor preference of the host cells to those of 2,6-linkage, found predominantly in humans' upper respiratory tract, in order to create an infection that could shed aerosolized virus particles. Such an infection must occur in the upper respiratory tract of humans, thus fundamentally undercutting the fatal trajectory of the disease. A study published in 2012 in Science Magazine reported on research findings that allowed for the airborne transmission of H5N1 in laboratory ferrets. The study in question created airborne H5N1 via amino acid substitutions that largely mitigated the devastating effects of the disease. This fact was underscored by the 0% fatality rate among the ferrets infected via airborne transmission, as well as the fundamental biology underlying the substitutions. Flu viruses attach to host cells via the hemagluttinin proteins on their envelope. These hemagluttinin proteins bind to sialic acid receptors on host cells, which can fall into two categories. The sialic acid receptors can be either 2,3 or 2,6-linked, with the species of origin largely deciding receptor preference. In influenzas of avian origin 2,3-linkage is preferred, vs. influenzas of human origin in which 2,6-linkage is preferable. 2,3-linked SA receptors in humans are found predominantly in the lower respiratory tract, a fact that is the primary foundation for the deadliness of avian influenzas in humans, and also the key to their lack of airborne transmission. In the study that created an airborne avian influenza among ferrets it was necessary to switch the receptor preference of the host cells to those of 2,6-linkage, found predominantly in humans' upper respiratory tract, in order to create an infection that could shed aerosolized virus particles. Such an infection must occur in the upper respiratory tract of humans, thus fundamentally undercutting the fatal trajectory of the disease. Influenza A virus subtype H7N9 is a novel avian influenza virus first reported to have infected humans in 2013 in China. Most of the reported cases of human infection have resulted in severe respiratory illness. In the month following the report of the first case, more than 100 people had been infected, an unusually high rate for a new infection; a fifth of those patients had died, a fifth had recovered, and the rest remained critically ill. The WHO has identified H7N9 as "...an unusually dangerous virus for humans." As of June 30, 133 cases have been reported, resulting in the deaths of 43. Research regarding background and transmission is ongoing. It has been established that many of the human cases of H7N9 appear to have a link to live bird markets. As of July 2013, there is no evidence of sustained human-to-human transmission. A study group headed by one of the world's leading experts on avian flu reported that several instances of human-to-human infection were suspected. It has been reported that H7N9 virus does not kill poultry, which will make surveillance much more difficult. Researchers have commented on the unusual prevalence of older males among H7N9-infected patients. While several environmental, behavioral, and biological explanations for this pattern have been proposed, as yet, the reason is unknown. Currently no vaccine exists, but the use of influenza antiviral drugs known as neuraminidase inhibitors in cases of early infection may be effective. The number of cases detected after April fell abruptly. The decrease in the number of new human H7N9 cases may have resulted from containment measures taken by Chinese authorities, including closing live bird markets, or from a change in seasons, or possibly a combination of both factors. Studies indicate that avian influenza viruses have a seasonal pattern, thus it is thought that infections may pick up again when the weather turns cooler in China. In the four years from early 2013 to early 2017, 916 lab-confirmed human cases of H7N9 were reported to the WHO. On 9 January 2017, the National Health and Family Planning Commission of China reported to the WHO 106 cases which occurred from late November through December. 29, 2016. The cases are reported from Jiangsu (52), Zhejiang (21), Anhui (14), Guangdong (14), Shanghai (2), Fujian (2) and Hunan (1). 80 of these 106 persons have visited live poultry markets. Of these cases, there have been 35 deaths. In two of the 106 cases, human-to-human transmission could not be ruled out. Affected prefectures in Jiangsu province closed live poultry markets in late December 2016, whereas Zhejiang, Guangdong and Anhui provinces went the route of strengthening live poultry market regulations. Travellers to affected regions are recommended to avoid poultry farms, live bird markets, and surfaces which appear to be contaminated with poultry feces. Similar sudden increases in the number of human cases of H7N9 have occurred in previous years during December and January. Several domestic species have been infected with and shown symptoms of H5N1 viral infection, including cats, dogs, ferrets, pigs, and birds. Attempts are made in the United States to minimize the presence of HPAI in poultry through routine surveillance of poultry flocks in commercial poultry operations. Detection of a HPAI virus may result in immediate culling of the flock. Less pathogenic viruses are controlled by vaccination, which is done primarily in turkey flocks ( ATCvet codes: QI01AA23 ( WHO ) for the inactivated fowl vaccine, QI01CL01 ( WHO ) for the inactivated turkey combination vaccine). Avian influenza in cats can show a variety of symptoms and usually lead to death. Cats are able to get infected by either consuming an infected bird or by contracting the virus from another infected cat. As of April 4, 2024, avian flu has been confirmed in seven dairy herds in Texas, three herds in Kansas, two in New Mexico, and one each in Ohio, Michigan, and Idaho. Since 2022, avian flu has been distributed worldwide by migratory birds. In this current April 2024 outbreak, one agricultural worker in Texas has also tested positive though only with the symptom of eye inflammation. Attempts are made in the United States to minimize the presence of HPAI in poultry through routine surveillance of poultry flocks in commercial poultry operations. Detection of a HPAI virus may result in immediate culling of the flock. Less pathogenic viruses are controlled by vaccination, which is done primarily in turkey flocks ( ATCvet codes: QI01AA23 ( WHO ) for the inactivated fowl vaccine, QI01CL01 ( WHO ) for the inactivated turkey combination vaccine). Avian influenza in cats can show a variety of symptoms and usually lead to death. Cats are able to get infected by either consuming an infected bird or by contracting the virus from another infected cat.As of April 4, 2024, avian flu has been confirmed in seven dairy herds in Texas, three herds in Kansas, two in New Mexico, and one each in Ohio, Michigan, and Idaho. Since 2022, avian flu has been distributed worldwide by migratory birds. In this current April 2024 outbreak, one agricultural worker in Texas has also tested positive though only with the symptom of eye inflammation. In 2005, the formation of the International Partnership on Avian and Pandemic Influenza was announced in order to elevate the importance of avian flu, coordinate efforts, and improve disease reporting and surveillance in order to better respond to future pandemics. New networks of laboratories have emerged to detect and respond to avian flu, such as the Crisis Management Center for Animal Health, the Global Avian Influenza Network for Surveillance, OFFLU , and the Global Early Warning System for major animal diseases. After the 2003 outbreak, WHO member states have also recognized the need for more transparent and equitable sharing of vaccines and other benefits from these networks. Cooperative measures created in response to HPAI have served as a basis for programs related to other emerging and re-emerging infectious diseases. HPAI control has also been used for political ends. In Indonesia, negotiations with global response networks were used to recentralize power and funding to the Ministry of Health. In Vietnam policymakers, with the support of the Food and Agriculture Organization of the United Nations (FAO) , used HPAI control to accelerate the industrialization of livestock production for export by proposing to increase the portion of large-scale commercial farms and reducing the number of poultry keepers from 8 to 2 million by 2010. In 2023, report by the Royal Society for the Protection of Birds (RSPB) and the British Trust for Ornithology 75% decrease in the Great Skua and a 25% reduction in Northern Gannets Backyard poultry production was viewed as "traditional Asian" agricultural practices that contrasted with modern commercial poultry production and seen as a threat to biosecurity. Backyard production appeared to hold greater risk than commercial production due to lack of biosecurity and close contact with humans, though HPAI spread in intensively raised flocks was greater due to high density rearing and genetic homogeneity. Asian culture itself was blamed as the reason why certain interventions, such as those that only looked at placed-based interventions, would fail without looking for multifaceted solutions. Press accounts of avian flu in Indonesia were seen by poultry farmers as conflating suspected cases while the public did see the accounts as informative, though many became de-sensitized to the idea of impending danger or only temporarily changed their poultry-related behavior. Rumors also circulated in Java in 2006. These tended to focus on bird flu being linked to big businesses in order to drive small farmers out of the market by exaggerating the danger of avian influenza, avian flu being introduced by foreigners to force Indonesians to purchase imported chicken and keep Indonesian chicken off the world market, and the government using avian flu as a ploy to attract funds from wealthy countries. Such rumors reflected concerns about big businesses, globalization, and a distrust of the national government in a country where "the amount of decentralization here is breathtaking" according to Steven Bjorge, a WHO epidemiologist in Jakarta in 2006. In the context a decentralized national government that the public did not completely trust, Indonesian Health Minister Siti Fadilah Supari announced in December 2006 that her government would no longer be sharing samples of H5N1 collected from Indonesian patients. This decision came as a shock to the international community as it disrupted the Global Influenza Surveillance Network (GISN) coordinated by the WHO for managing seasonal and pandemic influenza. GISN is based on countries sharing virus specimens freely with the WHO which assesses and eventually sends these samples to pharmaceutical companies in order to produce vaccines that are sold back to these countries. Though this was initially seen as an attempt to protect national sovereignty at all costs, it was instead used for a domestic political struggle. Prior to Indonesia's dispute with the GISN, the Ministry of Health, already weak due to the decentralized nature the government, was experiencing further leakage of funding to state and non-state agencies due to global health interventions. By reasserting control over public health issues and funding by setting itself up as the sole Indonesian representative to the WHO, the Ministry of Health made itself a key player in the management of future international funds relating vaccine production and renegotiated benefits from global surveillance networks. Approximately 20% of the protein consumed in developing countries come from poultry. In the wake of the H5N1 pandemic, millions of poultry were killed. In Vietnam alone, over 50 million domestic birds were killed due to HPAI infection and control attempts. A 2005 report by the FAO totaled economic losses in South East Asia around US$10 billion. This had the greatest impact on small scale commercial and backyard producers relative to total assets compared to industrial chains which primarily experience temporary decreases in exports and loss of consumer confidence. Some governments did provide compensation for culled poultry, it was often far below market value (close to 30% of market value in Vietnam), while others such as Cambodia provide no compensation to farmers at all. As poultry serves as a source of food security and liquid assets, the most vulnerable populations were poor small scale farmers. The loss of birds due to HPAI and culling in Vietnam led to an average loss of 2.3 months of production and US$69–108 for households where many have an income of $2 a day or less. The loss of food security for vulnerable households can be seen in the stunting of children under five in Egypt. Women are another population at risk as in most regions of the world, small flocks are tended to by women. Widespread culling also resulted in the decreased enrollment of girls in school in Turkey. Backyard poultry production was viewed as "traditional Asian" agricultural practices that contrasted with modern commercial poultry production and seen as a threat to biosecurity. Backyard production appeared to hold greater risk than commercial production due to lack of biosecurity and close contact with humans, though HPAI spread in intensively raised flocks was greater due to high density rearing and genetic homogeneity. Asian culture itself was blamed as the reason why certain interventions, such as those that only looked at placed-based interventions, would fail without looking for multifaceted solutions. Press accounts of avian flu in Indonesia were seen by poultry farmers as conflating suspected cases while the public did see the accounts as informative, though many became de-sensitized to the idea of impending danger or only temporarily changed their poultry-related behavior. Rumors also circulated in Java in 2006. These tended to focus on bird flu being linked to big businesses in order to drive small farmers out of the market by exaggerating the danger of avian influenza, avian flu being introduced by foreigners to force Indonesians to purchase imported chicken and keep Indonesian chicken off the world market, and the government using avian flu as a ploy to attract funds from wealthy countries. Such rumors reflected concerns about big businesses, globalization, and a distrust of the national government in a country where "the amount of decentralization here is breathtaking" according to Steven Bjorge, a WHO epidemiologist in Jakarta in 2006. In the context a decentralized national government that the public did not completely trust, Indonesian Health Minister Siti Fadilah Supari announced in December 2006 that her government would no longer be sharing samples of H5N1 collected from Indonesian patients. This decision came as a shock to the international community as it disrupted the Global Influenza Surveillance Network (GISN) coordinated by the WHO for managing seasonal and pandemic influenza. GISN is based on countries sharing virus specimens freely with the WHO which assesses and eventually sends these samples to pharmaceutical companies in order to produce vaccines that are sold back to these countries. Though this was initially seen as an attempt to protect national sovereignty at all costs, it was instead used for a domestic political struggle. Prior to Indonesia's dispute with the GISN, the Ministry of Health, already weak due to the decentralized nature the government, was experiencing further leakage of funding to state and non-state agencies due to global health interventions. By reasserting control over public health issues and funding by setting itself up as the sole Indonesian representative to the WHO, the Ministry of Health made itself a key player in the management of future international funds relating vaccine production and renegotiated benefits from global surveillance networks.Approximately 20% of the protein consumed in developing countries come from poultry. In the wake of the H5N1 pandemic, millions of poultry were killed. In Vietnam alone, over 50 million domestic birds were killed due to HPAI infection and control attempts. A 2005 report by the FAO totaled economic losses in South East Asia around US$10 billion. This had the greatest impact on small scale commercial and backyard producers relative to total assets compared to industrial chains which primarily experience temporary decreases in exports and loss of consumer confidence. Some governments did provide compensation for culled poultry, it was often far below market value (close to 30% of market value in Vietnam), while others such as Cambodia provide no compensation to farmers at all. As poultry serves as a source of food security and liquid assets, the most vulnerable populations were poor small scale farmers. The loss of birds due to HPAI and culling in Vietnam led to an average loss of 2.3 months of production and US$69–108 for households where many have an income of $2 a day or less. The loss of food security for vulnerable households can be seen in the stunting of children under five in Egypt. Women are another population at risk as in most regions of the world, small flocks are tended to by women. Widespread culling also resulted in the decreased enrollment of girls in school in Turkey. People who do not regularly come into contact with birds are not at high risk for contracting avian influenza. Those at high risk include poultry farm workers, animal control workers, wildlife biologists, and ornithologists who handle live birds. Organizations with high-risk workers should have an avian influenza response plan in place before any cases have been discovered. Biosecurity of poultry flocks is also important for prevention. Flocks should be isolated from outside birds, especially wild birds, and their waste; vehicles used around the flock should be regularly disinfected and not shared between farms; and birds from slaughter channels should not be returned to the farm. With proper infection control and use of personal protective equipment (PPE), the chance for infection is low. Protecting the eyes, nose, mouth, and hands is important for prevention because these are the most common ways for the virus to enter the body. Appropriate personal protective equipment includes aprons or coveralls, gloves, boots or boot covers, and a head cover or hair cover. Disposable PPE is recommended. An N-95 respirator and unvented/indirectly vented safety goggles are also part of appropriate PPE. A powered air purifying respirator (PAPR) with hood or helmet and face shield is also an option. Proper reporting of an isolated case can help to prevent spread. The Centers for Disease Control and Prevention (US) recommendation is that if a worker develops symptoms within 10 days of working with infected poultry or potentially contaminated materials, they should seek care and notify their employer, who should notify public health officials. For future avian influenza threats, the WHO suggests a three-phase, five-part plan. Phase 1: Pre-pandemic Reduce opportunities for human infection Strengthen the early warning system Phase 2: Emergence of a pandemic virus Contain or delay spread at the source Phase 3: Pandemic declared and spreading internationally Reduce morbidity, mortality, and social disruption Conduct research to guide response measures Reduce opportunities for human infection Strengthen the early warning system Contain or delay spread at the source Reduce morbidity, mortality, and social disruption Conduct research to guide response measures Vaccines for poultry have been formulated against several of the avian H5N1 influenza varieties. Control measures for HPAI encourage mass vaccinations of poultry though The World Health Organization has compiled a list of known clinical trials of pandemic influenza prototype vaccines, including those against H5N1. In some countries still at high risk for HPAI spread, there is compulsory strategic vaccination though vaccine supply shortages remain a problem. During the initial response to H5N1, a one size fits all recommendation was used for all poultry production systems, though measures for intensively raised birds were not necessarily appropriate for extensively raised birds. When looking at village-raised poultry, it was first assumed that the household was the unit and that flocks did not make contact with other flocks, though more effective measures came into use when the epidemiological unit was the village. Recommendations involve restructuring commercial markets to improve biosecurity against avian influenza. Poultry production zoning is used to limit poultry farming to specific areas outside of urban environments while live poultry markets improve biosecurity by limiting the number of traders holding licenses and subjecting producers and traders to more stringent inspections. These recommendations in combination with requirements to fence and house all poultry, and to limit free ranging flocks, will eventually lead to fewer small commercial producers and backyard producers, costing livelihoods as they are unable to meet the conditions needed to participate. A summary of reports to the World Organisation for Animal Health in 2005 and 2010 suggest that surveillance and under-reporting in developed and developing countries is still a challenge. Often, donor support can focus on HPAI control alone, while similar diseases such as Newcastle disease , acute fowl cholera , infectious laryngotracheitis, and infectious bursal disease still affect poultry populations. When HPAI tests come back negative, a lack of funded testing for differential diagnoses can leave farmers wondering what killed their birds. Since traditional production systems require little investment and serve as a safety net for lower income households, prevention and treatment can be seen as less cost-effective than letting poultry die. Effective control not only requires prior agreements to be made with relevant government agencies, such as seen with Indonesia, they must also not unduly threaten food security. Culling is used in order to decrease the threat of avian influenza transmission by killing potentially infected birds. The FAO manual on HPAI control recommends a zoning strategy which begins with the identification of an infected area (IA) where sick or dead birds have tested positive. All poultry in this zone are culled while the area 1 to 5 km from the outer boundary of the IA is considered the restricted area (RA) placed under strict surveillance. 2 to 10 km from the RA is the control area (CA) that serves as a buffer zone in case of spread. Culling is not recommended beyond the IA unless there is evidence of spread. The manual also provides examples of how control was carried out between 2004 and 2005 to contain H5N1 where all poultry was to be stamped out in a 3 km radius beyond the infected point and beyond that a 5 km radius where all fowl was to be vaccinated. This culling method was indiscriminate as a large proportion of the poultry inside these areas were small backyard flocks which did not travel great enough distances to carry infection to adjacent villages without human effort and may have not been infected at all. Between 2004 and 2005, over 100 million chickens were culled in Asia to contain H5N1. The risk of mass culling of birds and the resulting economic impact led to farmers who were reluctant to report sick poultry. The culls often preempted actual lab testing for H5N1 as avian flu policy justified sacrificing poultry as a safeguard against HPAI spread. In response to these policies, farmers in Vietnam between 2003 and 2004 became more and more unwilling to surrender apparently healthy birds to authorities and stole poultry destined for culls as it stripped poultry of their biosocial and economic worth. By the end of 2005, the government implemented a new policy that targeted high-risk flock in the immediate vicinity of infected farms and instituted voluntary culling with compensation in the case of a local outbreak. Not only did culling result in severe economic impacts especially for small scale farmers, culling itself may be an ineffective preventative measure. In the short-term, mass culling achieves its goals of limiting the immediate spread of HPAI, it has been found to impede the evolution of host resistance which is important for the long-term success of HPAI control. Mass culling also selects for elevated influenza virulence and results in the greater mortality of birds overall. Effective culling strategies must be selective as well as considerate of economic impacts to optimize epidemiological control and minimize economic and agricultural destruction. Prevention and control programs must take into account local understandings of people-poultry relations. In the past, programs that have focused on singular, place-based understandings of disease transmission have been ineffective. In the case of Northern Vietnam, health workers saw poultry as commodities with an environment that was under the control of people. Poultry existed in the context of farms, markets, slaughterhouses, and roads while humans were indirectly the primary transmitters of avian flu, placing the burden of disease control on people. Farmers saw their free ranging poultry in an environment dominated by nonhuman forces that they could not exert control over. There were a host of nonhuman actors such as wild birds and weather patterns whose relationships with the poultry fostered the disease and absolved farmers of complete responsibility for disease control. Attempts at singular, place-based controls sought to teach farmers to identify areas where their behavior could change without looking at poultry behaviors. Behavior recommendations by Vietnam's National Steering Committee for Avian Influenza Control and Prevention (NSCAI) were drawn from the FAO Principles of Biosecurity. These included restrictions from entering areas where poultry are kept by erecting barriers to segregate poultry from non-human contact, limits on human movement of poultry and poultry-related products ideally to transporters, and recommendations for farmers to wash hands and footwear before and after contact with poultry. Farmers, pointed to wind and environmental pollution as reasons poultry would get sick. NSCAI recommendations also would disrupt longstanding livestock production practices as gates impede sales by restricting assessment of birds by appearance and offend customers by limiting outside human contact. Instead of incorporating local knowledge into recommendations, cultural barriers were used as scapegoats for failed interventions. Prevention and control methods have been more effective when also considering the social, political, and ecological agents in play. During the initial response to H5N1, a one size fits all recommendation was used for all poultry production systems, though measures for intensively raised birds were not necessarily appropriate for extensively raised birds. When looking at village-raised poultry, it was first assumed that the household was the unit and that flocks did not make contact with other flocks, though more effective measures came into use when the epidemiological unit was the village. Recommendations involve restructuring commercial markets to improve biosecurity against avian influenza. Poultry production zoning is used to limit poultry farming to specific areas outside of urban environments while live poultry markets improve biosecurity by limiting the number of traders holding licenses and subjecting producers and traders to more stringent inspections. These recommendations in combination with requirements to fence and house all poultry, and to limit free ranging flocks, will eventually lead to fewer small commercial producers and backyard producers, costing livelihoods as they are unable to meet the conditions needed to participate. A summary of reports to the World Organisation for Animal Health in 2005 and 2010 suggest that surveillance and under-reporting in developed and developing countries is still a challenge. Often, donor support can focus on HPAI control alone, while similar diseases such as Newcastle disease , acute fowl cholera , infectious laryngotracheitis, and infectious bursal disease still affect poultry populations. When HPAI tests come back negative, a lack of funded testing for differential diagnoses can leave farmers wondering what killed their birds. Since traditional production systems require little investment and serve as a safety net for lower income households, prevention and treatment can be seen as less cost-effective than letting poultry die. Effective control not only requires prior agreements to be made with relevant government agencies, such as seen with Indonesia, they must also not unduly threaten food security. Culling is used in order to decrease the threat of avian influenza transmission by killing potentially infected birds. The FAO manual on HPAI control recommends a zoning strategy which begins with the identification of an infected area (IA) where sick or dead birds have tested positive. All poultry in this zone are culled while the area 1 to 5 km from the outer boundary of the IA is considered the restricted area (RA) placed under strict surveillance. 2 to 10 km from the RA is the control area (CA) that serves as a buffer zone in case of spread. Culling is not recommended beyond the IA unless there is evidence of spread. The manual also provides examples of how control was carried out between 2004 and 2005 to contain H5N1 where all poultry was to be stamped out in a 3 km radius beyond the infected point and beyond that a 5 km radius where all fowl was to be vaccinated. This culling method was indiscriminate as a large proportion of the poultry inside these areas were small backyard flocks which did not travel great enough distances to carry infection to adjacent villages without human effort and may have not been infected at all. Between 2004 and 2005, over 100 million chickens were culled in Asia to contain H5N1. The risk of mass culling of birds and the resulting economic impact led to farmers who were reluctant to report sick poultry. The culls often preempted actual lab testing for H5N1 as avian flu policy justified sacrificing poultry as a safeguard against HPAI spread. In response to these policies, farmers in Vietnam between 2003 and 2004 became more and more unwilling to surrender apparently healthy birds to authorities and stole poultry destined for culls as it stripped poultry of their biosocial and economic worth. By the end of 2005, the government implemented a new policy that targeted high-risk flock in the immediate vicinity of infected farms and instituted voluntary culling with compensation in the case of a local outbreak. Not only did culling result in severe economic impacts especially for small scale farmers, culling itself may be an ineffective preventative measure. In the short-term, mass culling achieves its goals of limiting the immediate spread of HPAI, it has been found to impede the evolution of host resistance which is important for the long-term success of HPAI control. Mass culling also selects for elevated influenza virulence and results in the greater mortality of birds overall. Effective culling strategies must be selective as well as considerate of economic impacts to optimize epidemiological control and minimize economic and agricultural destruction.Prevention and control programs must take into account local understandings of people-poultry relations. In the past, programs that have focused on singular, place-based understandings of disease transmission have been ineffective. In the case of Northern Vietnam, health workers saw poultry as commodities with an environment that was under the control of people. Poultry existed in the context of farms, markets, slaughterhouses, and roads while humans were indirectly the primary transmitters of avian flu, placing the burden of disease control on people. Farmers saw their free ranging poultry in an environment dominated by nonhuman forces that they could not exert control over. There were a host of nonhuman actors such as wild birds and weather patterns whose relationships with the poultry fostered the disease and absolved farmers of complete responsibility for disease control. Attempts at singular, place-based controls sought to teach farmers to identify areas where their behavior could change without looking at poultry behaviors. Behavior recommendations by Vietnam's National Steering Committee for Avian Influenza Control and Prevention (NSCAI) were drawn from the FAO Principles of Biosecurity. These included restrictions from entering areas where poultry are kept by erecting barriers to segregate poultry from non-human contact, limits on human movement of poultry and poultry-related products ideally to transporters, and recommendations for farmers to wash hands and footwear before and after contact with poultry. Farmers, pointed to wind and environmental pollution as reasons poultry would get sick. NSCAI recommendations also would disrupt longstanding livestock production practices as gates impede sales by restricting assessment of birds by appearance and offend customers by limiting outside human contact. Instead of incorporating local knowledge into recommendations, cultural barriers were used as scapegoats for failed interventions. Prevention and control methods have been more effective when also considering the social, political, and ecological agents in play.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Timeline_of_influenza/html

Timeline of influenza

This is a timeline of influenza , briefly describing major events such as outbreaks , epidemics , pandemics , discoveries and developments of vaccines . In addition to specific year/period-related events, there is the seasonal flu that kills between 250,000 and 500,000 people every year and has claimed between 340 million and 1 billion human lives throughout history. The 1557 influenza pandemic spread from Asia to the Ottoman Empire , then Europe, the Americas , and Africa. This flu pandemic is the first to be reliably recorded as spreading worldwide, is when flu received its first English names. It is also the first pandemic in which flu is linked to miscarriages. The pandemic lasted for at least two years. : 307–308 The 1580 pandemic is well-documented, with high mortality recorded as influenza spreads across Europe. Influenza has been studied by countless physicians, epidemiologists, and medical historians. Chroniclers distinguished its outbreaks from other diseases by the rapid, indiscriminate way it struck down entire populations. Flu has been called various names including tac , coqueluche , the new disease , gruppie , grippe , castrone , : 17 influenza , and commonly just catarrh by many chroniclers and physicians throughout the ages. The disease seems to have been present in the northeast United States as early as October 1732, after which reports of it came out of Newfoundland , Barbados , Jamaica , Mexico , Peru , and Chile . : 9 : 23 The following month it appeared in Germany, reportedly coming from Russia through Poland . : 23 It spread throughout Germany in November and into December, when it caused outbreaks in Switzerland and Holland through the end of the year. : 23 Notably, it was reported on the Isle of Bourbon , off of Madagascar , in December as well. : 9 It prevailed in London and Paris in January 1733, as well as the Netherlands ; that same month, it was reported in Italy, where it continued into March. : 9 Madrid was visited in February. : 9 Though the name had been used in English before, this was the first time "influenza" was broadly used to refer to the disease. While it prevailed extensively in Italy, the rumor of a "great epidemic" of "influenza" in that country spread faster than the disease itself, and the name came to be used in England, at least for the duration of the outbreak. Once it had passed, the name fell out of common use. : 304 On the whole, the epidemic was notable for seeming to follow no clear path, "being reported now here, now there," : 27 and for missing certain locales altogether, such as Paris. : 358 Morbidity was "great" where the disease did strike. : 27 Mortality was relatively low, though it did vary, with some cities seeing more severe epidemics than others even within the same country. : 27 : 358 Spontaneous abortions and premature births were reported as new complications during this pandemic, which can be taken as a piece of supporting evidence that this was indeed a pandemic of influenza, in addition to its high attack rate and broad distribution across at least two continents. : 27 Other authors, however, consider only the 1781–1782 experience to be a true pandemic. : 18 : 30 : 27 If anything, the outbreaks in Russia and North America in 1780–1781 were possible "herald waves" of the later, greater epidemic. : 27 During this true pandemic period, influenza is said to have first broken out in China and British India in the fall of 1781. : 11 By the winter, it was sweeping through Siberia and Russia, visiting St. Petersburg again in January 1782. : 11 It moved through Germany between February and June. : 11 It struck Finland in February and Denmark, Sweden, and Hungary in April. After reaching England as early as April, influenza broke out in London and other parts in May and was general in England and Scotland in June. : 11 After hitting the Netherlands in May, it spread to France and then to Italy, where it broke out in June. : 30 Finally, it reached Spain by August, prevailing in Madrid and other parts. : 11 This epidemic solidified "influenza" as the name of the disease in English. Although first used generally in 1743 to refer to the affliction epidemic in Italy at the time, it was not until an epidemic in 1775 that the term began to be used again more generally, and by 1782, it was the typical name applied. In the summer of that year, when the disease hit England, the Royal College of Physicians formally adopted the Italian word as the official name. : 362 The influenza was first reported in Russia in March 1788, in St. Petersburg and Kherson and in Poland. : 11 It then spread westward, invading Germany, Hungary, Denmark, England, Scotland, France, and Italy successively throughout the year and being reported finally in Switzerland in October. : 11 Observed influenza activity then remained low for nearly a year before the disease appeared in the Western Hemisphere, breaking out in the US states of Georgia and New York in September 1789. : 11 The epidemic crossed the entire United States in six to eight weeks. : 290 It was reported in Jamaica in October : 11 and Grenada in November, : 256–257 and by the end of the year it was prevalent in Nova Scotia and South America . : 11 After a short reprieve, the influenza resumed epidemic proportions in the spring of 1790 in the northeast United States and perhaps some other parts, : 12 declining about the first week of June. : 259 There is some evidence of increased severity during the spring wave as compared to the fall one. : 291 The disease was prevalent again in Philadelphia and neighboring counties in Pennsylvania , and was observed as well in Virginia and Rhode Island , in the winter of 1790–1791, but it was not nearly as widespread as its first two appearances. : 260

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Pandemic influenza

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Influenza treatment

Treatments for influenza include a range of medications and therapies that are used in response to disease influenza . Treatments may either directly target the influenza virus itself; or instead they may just offer relief to symptoms of the disease, while the body's own immune system works to recover from infection. The main classes of antiviral drugs used against influenza are neuraminidase inhibitors , such as zanamivir and oseltamivir , polymerase acidic endonuclease inhibitors such as baloxavir marboxil , or inhibitors of the viral M2 protein , such as amantadine and rimantadine . These drugs can reduce the severity of symptoms if taken soon after infection and can also be taken to decrease the risk of infection. However, virus strains have emerged that show drug resistance to some classes of drug.The United States authority on disease prevention, the Centers for Disease Control and Prevention (CDC), recommends that people with influenza infections: Stay at home Get plenty of rest Drink a lot of liquids Do not smoke or drink alcohol Consider over-the-counter medications to relieve flu symptoms Consult a physician early on for best possible treatment Remain alert for emergency warning signs Warning signs are symptoms that indicate that the disease is becoming serious and needs immediate medical attention. These include: [ citation needed ] Difficulty breathing or shortness of breath Pain or pressure in the chest or abdomen Dizziness Confusion Severe or persistent vomiting In children other warning signs include irritability, failing to wake up and interact, rapid breathing, and a blueish skin color. Another warning sign in children is if the flu symptoms appear to resolve, but then reappear with fever and a bad cough. Antiviral drugs directly target the viruses responsible for influenza infections. Generally, anti-viral drugs work optimally when taken within a few days of the onset of symptoms. Certain drugs are used prophylactically , that is they are used in uninfected individuals to guard against infection. [ medical citation needed ] Four licensed influenza antiviral agents are available in the United States: zanamivir , oseltamivir phosphate , peramivir , and baloxavir marboxil . They are available through prescription only. In Russia and China a drug called arbidol is also used as a treatment. Testing of the drug has predominantly occurred in these countries and, although no clinical trials have been published demonstrating this is an effective drug, some data suggest that this could be a useful treatment for influenza. Interferons are cellular signalling factors produced in response to viral infection. Research into the use of interferons to combat influenza began in the 1960s in the Soviet Union , culminating in a trial of 14,000 subjects at the height of the Hong Kong Flu of 1969, in which those treated prophylactically with interferon were more than 50% less likely to suffer symptoms, though evidence of latent infection was present. In these early studies leukocytes were collected from donated blood and exposed to a high dose of Newcastle disease , causing them to release interferons. Although interferon therapies became widespread in the Soviet Union, the method was doubted in the United States after high doses of interferon proved ineffective in trials. Though the 1969 study used 256 units of interferon, subsequent studies used up to 8.4 million units. It has since been proposed that activity of interferon is highest at low concentrations. Phase III trials in Australia are planned for 2010, and initial trials are planned in the U.S. for late 2009. Interferons have also been investigated as adjuvants to enhance to effectiveness of influenza vaccines . This work was based on experiments in mice that suggested that type I interferons could enhance the effectiveness of influenza vaccines in mice. However, a clinical trial in 2008 found that oral dosing of elderly patients with interferon-alpha actually reduced their immune response to an influenza vaccine. Viferon is a suppository of (non- pegylated ) interferon alpha -2b, ascorbic acid (vitamin C), and tocopherol (vitamin E) which was reported in two small studies to be as effective as arbidol. Another interferon alfa-2b medicine, "Grippferon", nasal drops, is used for treatment and emergency prevention of Influenza and cold. Its manufacturers have appealed to the WHO to consider its use against avian influenza and H1N1 Influenza 09 (Human Swine Flu), stating that it was used successfully in Russia for eight years, but that "the medical profession in Europe and the USA is not informed about this medicine". Interferons are cellular signalling factors produced in response to viral infection. Research into the use of interferons to combat influenza began in the 1960s in the Soviet Union , culminating in a trial of 14,000 subjects at the height of the Hong Kong Flu of 1969, in which those treated prophylactically with interferon were more than 50% less likely to suffer symptoms, though evidence of latent infection was present. In these early studies leukocytes were collected from donated blood and exposed to a high dose of Newcastle disease , causing them to release interferons. Although interferon therapies became widespread in the Soviet Union, the method was doubted in the United States after high doses of interferon proved ineffective in trials. Though the 1969 study used 256 units of interferon, subsequent studies used up to 8.4 million units. It has since been proposed that activity of interferon is highest at low concentrations. Phase III trials in Australia are planned for 2010, and initial trials are planned in the U.S. for late 2009. Interferons have also been investigated as adjuvants to enhance to effectiveness of influenza vaccines . This work was based on experiments in mice that suggested that type I interferons could enhance the effectiveness of influenza vaccines in mice. However, a clinical trial in 2008 found that oral dosing of elderly patients with interferon-alpha actually reduced their immune response to an influenza vaccine. Viferon is a suppository of (non- pegylated ) interferon alpha -2b, ascorbic acid (vitamin C), and tocopherol (vitamin E) which was reported in two small studies to be as effective as arbidol. Another interferon alfa-2b medicine, "Grippferon", nasal drops, is used for treatment and emergency prevention of Influenza and cold. Its manufacturers have appealed to the WHO to consider its use against avian influenza and H1N1 Influenza 09 (Human Swine Flu), stating that it was used successfully in Russia for eight years, but that "the medical profession in Europe and the USA is not informed about this medicine". Influenza viruses can show resistance to anti-viral drugs. Like the development of bacterial antibiotic resistance , this can result from over-use of these drugs. For example, a study published in the June 2009 Issue of Nature Biotechnology emphasized the urgent need for augmentation of oseltamivir (Tamiflu) stockpiles with additional antiviral drugs including zanamivir (Relenza) based on an evaluation of the performance of these drugs in the scenario that the 2009 H1N1 'Swine Flu' neuraminidase (NA) were to acquire the tamiflu-resistance (His274Tyr) mutation which is currently widespread in seasonal H1N1 strains. Yet another example is in the case of the amantadines treatment may lead to the rapid production of resistant viruses, and over-use of these drugs has probably contributed to the spread of resistance. In particular, this high-level of resistance may be due to the easy availability of amantadines as part of over-the-counter cold remedies in countries such as China and Russia, and their use to prevent outbreaks of influenza in farmed poultry. On the other hand, a few strains resistant to neuraminidase inhibitors have emerged and circulated in the absence of much use of the drugs involved, and the frequency with which drug resistant strains appears shows little correlation with the level of use of these drugs. However, laboratory studies have shown that it is possible for the use of sub-optimal doses of these drugs as a prophylactic measure might contribute to the development of drug resistance. During the United States 2005–2006 influenza season, increasing incidence of drug resistance by strain H3N2 to amantadine and rimantadine led the CDC to recommend oseltamivir as a prophylactic drug, and the use of either oseltamivir or zanamivir as treatment. Antiviral drugs are prescription-only medication in the United States. Readily available over-the-counter medications do not directly affect the disease, but they do provide relief from influenza symptoms, as illustrated in the table below. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin as taking aspirin in the presence of influenza infection (especially Influenzavirus B ) can lead to Reye syndrome , a rare but potentially fatal disease of the brain. Several generic prescription medications might prove useful to treat a potential H5N1 avian flu outbreak, including statins , fibrates , and chloroquine . Malnutrition can reduce the ability of the body to resist infections and is a common cause of immunodeficiency in the developing world. For instance, in a study in Ecuador , micronutrient deficiencies were found to be common in the elderly, especially for vitamin C , vitamin D , vitamin B-6 , vitamin B-12 , folic acid , and zinc , and these are thought to weaken the immune system or cause anemia and thus place people at greater risk of respiratory infections such as influenza. Seasonal variation in sunlight exposure, which is required for vitamin D synthesis within the body, has been proposed as one of the factors accounting for the seasonality of influenza. A meta-analysis of 13 studies indicated some support for adjunctive vitamin D therapy for influenza, but called for more rigorous clinical trials to settle the issue conclusively. A recent review discussing herbal and alternative medicines in influenza treatment details evidence suggesting that N-acetylcysteine , elderberry , or a combination of Eleutherococcus senticosus and Andrographis paniculata may help to shorten the course of influenza infection. The article cites more limited evidence including animal or in vitro studies to suggest possible benefit from vitamin C, DHEA , high lactoferrin whey protein , Echinacea spp., Panax quinquefolium , Larix occidentalis arabinogalactans , elenolic acid (a constituent of olive leaf extract ), Astragalus membranaceus , and Isatis tinctoria or Isatis indigotica . Another review assessed the quality of evidence for alternative influenza treatments, it concluded that there was "no compelling evidence" that any of these treatments were effective and that the available data on these products is particularly weak, with trials in this area suffering from many shortcomings, such as being small and poorly-designed and not testing for adverse effects. The activity of N-acetylcysteine (NAC) against influenza was first suggested in 1966. In 1997 a randomized clinical trial found that volunteers taking 1.2 grams of N-acetylcysteine daily for six months were as likely as those taking placebo to be infected by influenza, but only 25% of them experienced clinical symptoms, as contrasted with 67% of the control group . The authors concluded that resistance to flu symptoms was associated with a shift in cell mediated immunity from anergy toward normoergy , as measured by the degree of skin reactivity to seven common antigens such as tetanus and Candida albicans . Several animal studies found that in a mouse model of lethal infection with a high dose of influenza, oral supplementation with one gram of N-acetylcysteine per kilogram of body weight daily increased the rate of survival, either when administered alone or in combination with the antiviral drugs ribavirin or oseltamivir. NAC was shown to block or reduce cytopathic effects in influenza-infected macrophages, to reduce DNA fragmentation ( apoptosis ) in equine influenza-infected canine kidney cells, and to reduce RANTES production in cultured airway cells in response to influenza virus by 18%. The compound has been proposed for treatment of influenza. A few news reports have suggested the use of an elderberry ( Sambucus nigra ) extract as a potential preventative against the 2009 flu pandemic . The preparation has been reported to reduce the duration of influenza symptoms by raising levels of cytokines. However, the use of the preparation has been described as "imprudent" when an influenza strain causes death in healthy adults by cytokine storm leading to primary viral pneumonia. The manufacturer cites a lack of evidence for cytokine-related risks, but labels the product only as an antioxidant and food supplement . The mixture of Eleutherococcus senticosus ("Siberian ginseng") and Andrographis paniculata , sold under the trade name Kan Jang, was reported in the Journal of Herbal Pharmacotherapy to outperform amantadine in reducing influenza-related sick time and complications in a Volgograd pilot study of 71 patients in 2003. Prior to this, an extract of Eleutherococcus senticosus was shown to inhibit replication of RNA but not DNA viruses in vitro . Among nine Chinese medicinal herbs tested, Andrographis paniculata was shown to be most effective in inhibiting RANTES secretion by H1N1 influenza infected cells in cell culture , with an IC 50 for the ethanol extract of 1.2 milligrams per liter. High dietary intake of green tea (specifically, catechins and theanine that is found in tea products) has been correlated with reduced risk of contracting influenza, as well as having an antiviral effect upon types A and B. Specifically, the high levels of epigallocatechin gallate, epicatechin gallate, and epigallocatechin present in green tea were found to inhibit influenza virus replication. Additionally, topical application has been suggested to possibly act as a mild disinfectant. Regular dietary intake of green tea has been associated with stronger immune response to infection, through the enhancement of T-Cell function. The activity of N-acetylcysteine (NAC) against influenza was first suggested in 1966. In 1997 a randomized clinical trial found that volunteers taking 1.2 grams of N-acetylcysteine daily for six months were as likely as those taking placebo to be infected by influenza, but only 25% of them experienced clinical symptoms, as contrasted with 67% of the control group . The authors concluded that resistance to flu symptoms was associated with a shift in cell mediated immunity from anergy toward normoergy , as measured by the degree of skin reactivity to seven common antigens such as tetanus and Candida albicans . Several animal studies found that in a mouse model of lethal infection with a high dose of influenza, oral supplementation with one gram of N-acetylcysteine per kilogram of body weight daily increased the rate of survival, either when administered alone or in combination with the antiviral drugs ribavirin or oseltamivir. NAC was shown to block or reduce cytopathic effects in influenza-infected macrophages, to reduce DNA fragmentation ( apoptosis ) in equine influenza-infected canine kidney cells, and to reduce RANTES production in cultured airway cells in response to influenza virus by 18%. The compound has been proposed for treatment of influenza. A few news reports have suggested the use of an elderberry ( Sambucus nigra ) extract as a potential preventative against the 2009 flu pandemic . The preparation has been reported to reduce the duration of influenza symptoms by raising levels of cytokines. However, the use of the preparation has been described as "imprudent" when an influenza strain causes death in healthy adults by cytokine storm leading to primary viral pneumonia. The manufacturer cites a lack of evidence for cytokine-related risks, but labels the product only as an antioxidant and food supplement . The mixture of Eleutherococcus senticosus ("Siberian ginseng") and Andrographis paniculata , sold under the trade name Kan Jang, was reported in the Journal of Herbal Pharmacotherapy to outperform amantadine in reducing influenza-related sick time and complications in a Volgograd pilot study of 71 patients in 2003. Prior to this, an extract of Eleutherococcus senticosus was shown to inhibit replication of RNA but not DNA viruses in vitro . Among nine Chinese medicinal herbs tested, Andrographis paniculata was shown to be most effective in inhibiting RANTES secretion by H1N1 influenza infected cells in cell culture , with an IC 50 for the ethanol extract of 1.2 milligrams per liter. High dietary intake of green tea (specifically, catechins and theanine that is found in tea products) has been correlated with reduced risk of contracting influenza, as well as having an antiviral effect upon types A and B. Specifically, the high levels of epigallocatechin gallate, epicatechin gallate, and epigallocatechin present in green tea were found to inhibit influenza virus replication. Additionally, topical application has been suggested to possibly act as a mild disinfectant. Regular dietary intake of green tea has been associated with stronger immune response to infection, through the enhancement of T-Cell function. An alternative to vaccination used in the 1918 flu pandemic was the direct transfusion of blood, plasma, or serum from recovered patients. Though medical experiments of the era lacked some procedural refinements, eight publications from 1918 to 1925 reported that the treatment could approximately halve the mortality in hospitalized severe cases with an average case-fatality rate of 37% when untreated. Bovine colostrum might also serve as a source of antibodies for some applications. Human T lymphocytes can be expanded in vitro using beads holding specific antigens to activate the cells and stimulate growth. Clonal populations of CD8+ cytotoxic T cells have been grown which carry T cell receptors specific to influenza. These work much like antibodies but are permanently bound to these cells. (See cellular immunity ) . High concentrations of N-acetylcysteine have been used to enhance growth of these cells. This method is still in early research. An alternative to vaccination used in the 1918 flu pandemic was the direct transfusion of blood, plasma, or serum from recovered patients. Though medical experiments of the era lacked some procedural refinements, eight publications from 1918 to 1925 reported that the treatment could approximately halve the mortality in hospitalized severe cases with an average case-fatality rate of 37% when untreated. Bovine colostrum might also serve as a source of antibodies for some applications. Human T lymphocytes can be expanded in vitro using beads holding specific antigens to activate the cells and stimulate growth. Clonal populations of CD8+ cytotoxic T cells have been grown which carry T cell receptors specific to influenza. These work much like antibodies but are permanently bound to these cells. (See cellular immunity ) . High concentrations of N-acetylcysteine have been used to enhance growth of these cells. This method is still in early research.

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Pandemic influenza

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Influenza A virus subtype H3N2

Influenza A virus subtype H3N2 ( A/H3N2 ) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predominant strain, there are more hospitalizations. H3N2 is a subtype of the viral genus Influenzavirus A , which is an important cause of human influenza . Its name derives from the forms of the two kinds of proteins on the surface of its coat, hemagglutinin (H) and neuraminidase (N). By reassortment , H3N2 exchanges genes for internal proteins with other influenza subtypes. Seasonal influenza kills an estimated 36,000 people in the United States each year. Flu vaccines are based on predicting which "mutants" of H1N1 , H3N2, H1N2 , and influenza B will proliferate in the next season. Separate vaccines are developed for the Northern and Southern Hemispheres in preparation for their annual epidemics. In the tropics, influenza shows no clear seasonality. In the past ten years, H3N2 has tended to dominate in prevalence over H1N1, H1N2, and influenza B. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. Seasonal H3N2 flu is a human flu from H3N2 that is slightly different from one of the previous year's flu season H3N2 variants. Seasonal influenza viruses flow out of overlapping epidemics in East Asia and Southeast Asia , then trickle around the globe before dying off. Identifying the source of the viruses allows global health officials to better predict which viruses are most likely to cause the most disease over the next year. An analysis of 13,000 samples of influenza A/H3N2 virus that were collected across six continents from 2002 to 2007 by the WHO's Global Influenza Surveillance Network showed the newly emerging strains of H3N2 appeared in East and Southeast Asian countries about six to nine months earlier than anywhere else. The strains generally reached Australia and New Zealand next, followed by North America and Europe. The new variants typically reached South America after an additional six to nine months, the group reported. A 2007 study reported: "In swine , three influenza A virus subtypes ( H1N1 , H3N2 , and H1N2 ) are circulating throughout the world. In the United States, the classic H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. Most H3N2 virus isolates are triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. Present vaccination strategies for swine influenza virus (SIV) control and prevention in swine farms typically include the use of one of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 had strong serologic cross-reactions with antiserum to three commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses." Avian influenza virus H3N2 is endemic in pigs in China , and has been detected in pigs in Vietnam, contributing to the emergence of new variant strains. Pigs can carry human influenza viruses, which can combine (i.e. exchange homologous genome subunits by genetic reassortment ) with H5N1 , passing genes and mutating into a form which can pass easily among humans. H3N2 evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000 humans. The dominant strain of annual flu in humans in January 2006 was H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 in humans had increased to 91% by 2005. In August 2004, researchers in China found H5N1 in pigs. The Hong Kong Flu was a flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift , in which genes from multiple subtypes reassorted to form a new virus. This pandemic of 1968 and 1969 killed an estimated one million people worldwide. The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population, with a low death rate. In the United States, about 100,000 people died. Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans (Belshe 2005). The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics . However, cross-immunity within and between subtypes of influenza is poorly understood. [ citation needed ] The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N2 infections in the late 19th century. The first record of the outbreak in Hong Kong appeared on 13 July 1968 in an area with a density of about 500 people per acre in an urban setting. The outbreak reached maximum intensity in two weeks, lasting six weeks in total. The virus was isolated in Queen Mary Hospital . Flu symptoms lasted four to five days. By July 1968, extensive outbreaks were reported in Vietnam and Singapore . By September 1968, it reached India, the Philippines, northern Australia and Europe. That same month, the virus entered California from United States troops returning from the Vietnam War . It reached Japan, Africa and South America in 1969. Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian province in China. A/Fujian (H3N2) human flu (from A/Fujian/411/2002(H3N2)-like flu virus strains) caused an unusually severe 2003–2004 flu season. This was due to a reassortment event that caused a minor clade to provide a haemagglutinin gene that later became part of the dominant strain in the 2002–2003 flu season. A/Fujian (H3N2) was made part of the trivalent influenza vaccine for the 2004–2005 flu season . The 2004–05 trivalent influenza vaccine for the United States contained: The vaccines produced for the 2005–2006 season used: The 2006–2007 influenza vaccine composition recommended by the World Health Organization on 15 February 2006 and the US FDA's Vaccines and Related Biological Products Advisory Committee on 17 February 2006 used: an A/New Caledonia/20/99 (H1N1)-like virus an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 strains) a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004 and B/Ohio/1/2005 strains which are of B/Victoria/2/87 lineage The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on 14 February 2007 was: "A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B." Many H3N2 viruses making people ill in this 2007–2008 flu season differ from the strains in the vaccine and may not be well covered by the vaccine strains. "The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved [notably] from the H3N2 strain in the vaccine—A/Wisconsin/67/2005." The composition of virus vaccines for use in the 2008–2009 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2008 was: As of May 30, 2009: "CDC has antigenically characterized 1,567 seasonal human influenza viruses [947 influenza A (H1), 162 influenza A (H3) and 458 influenza B viruses] collected by U.S. laboratories since October 1, 2008, and 84 novel influenza A (H1N1) viruses. All 947 influenza seasonal A (H1) viruses are related to the influenza A (H1N1) component of the 2008–09 influenza vaccine (A/Brisbane/59/2007). All 162 influenza A (H3N2) viruses are related to the A (H3N2) vaccine component (A/Brisbane/10/2007). All 84 novel influenza A (H1N1) viruses are related to the A/California/07/2009 (H1N1) reference virus selected by WHO as a potential candidate for novel influenza A (H1N1) vaccine. Influenza B viruses currently circulating can be divided into two distinct lineages represented by the B/Yamagata/16/88 and B/Victoria/02/87 viruses. Sixty-one influenza B viruses tested belong to the B/Yamagata lineage and are related to the vaccine strain (B/Florida/04/2006). The remaining 397 viruses belong to the B/Victoria lineage and are not related to the vaccine strain." The vaccines produced for the 2009–2010 season used: an A/Brisbane/59/2007(H1N1)-like virus an A/Brisbane/10/2007 (H3N2)-like virus a B/Brisbane 60/2008-like antigens A separate vaccine was available for pandemic H1N1 influenza using the A/California/7/2009-like pandemic H1N1 strain. The vaccines produced for the 2010–2011 season used: an A/California/7/2009-like (pandemic H1N1) an A/Perth/16/2009-like (H3N2)-like virus a B/Brisbane/60/2008-like antigens The vaccines produced for the 2011–2012 season used: an A/California/07/2009 (H1N1)-like virus an A/Victoria/210/2009 (an A/Perth/16/2009-like strain) (H3N2)-like virus a B/Brisbane/60/2008-like virus The vaccines produced for the Northern Hemisphere 2012–2013 season used: In January 2013, influenza activity continued to increase in the United States and most of the country experienced high levels of influenza-like-illness (ILI), according to CDC's latest FluView report. Reports of influenza-like-illness (ILI) are nearing what have been peak levels during moderately severe seasons, and CDC continues to recommend influenza vaccination and antiviral drug treatment when appropriate at this time. On January 9, 2013, the Boston Government declared a public health emergency for H3N2 influenza. The vaccines produced for the Northern Hemisphere 2014–2015 season used: A/California/7/2009 (H1N1)pdm09-like virus A/Texas/50/2012 (H3N2)-like virus B/Massachusetts/2/2012-like virus, Quadrivalent vaccines include a B/Brisbane/60/2008-like virus. The CDC announced that drift variants of the A (H3N2) virus strain from the 2012–2013 potentially foretold a severe flu season for 2014–2015. The vaccines produced for the Northern Hemisphere 2015–2016 season used: A/California/7/2009 (H1N1)pdm09-like virus A/Switzerland/9715293/2013 (H3N2)-like virus B/Phuket/3073/2013-like virus. (This is a B/Yamagata lineage virus) The "Split Virion" vaccine distributed in 2016 contained the following strains of inactivated virus: A/California/7/2009 (H1N1)pdm09 - like strain (A/California/7/2009, NYMC X-179A) A/Hong Kong/4801/2014 (H3N2) - like strain (A/Hong Kong/4801/2014, NYMC X-263B) B/Brisbane/60/2008 - like strain (B/Brisbane/60/2008, wild type) A/California/7/2009 (H1N1)pdm09-like virus, A/Hong Kong/4801/2014 (H3N2)-like virus B/Brisbane/60/2008-like virus (B/Victoria lineage) Quadrivalent influenza vaccine adds: B/Phuket/3073/2013-like strain A/Michigan/45/2015 (H1N1)pdm09-like virus A/Hong Kong/4801/2014 (H3N2) B/Brisbane/60/2008-like virus (B/Victoria lineage) Quadrivalent influenza vaccine adds B/Phuket/3073/2013-like[B/Yamagata lineage] Quadrivalent - A/Brisbane/02/2018 (H1N1)pdm09-like virus A/SouthAustralia/34/2019 (H3N2)-like virus B/Washington/02/2019-like virus [B/Victoria lineage] B/Phuket/3073/2013-like virus [B/Yamagata lineage]The Hong Kong Flu was a flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift , in which genes from multiple subtypes reassorted to form a new virus. This pandemic of 1968 and 1969 killed an estimated one million people worldwide. The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population, with a low death rate. In the United States, about 100,000 people died. Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans (Belshe 2005). The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics . However, cross-immunity within and between subtypes of influenza is poorly understood. [ citation needed ] The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N2 infections in the late 19th century. The first record of the outbreak in Hong Kong appeared on 13 July 1968 in an area with a density of about 500 people per acre in an urban setting. The outbreak reached maximum intensity in two weeks, lasting six weeks in total. The virus was isolated in Queen Mary Hospital . Flu symptoms lasted four to five days. By July 1968, extensive outbreaks were reported in Vietnam and Singapore . By September 1968, it reached India, the Philippines, northern Australia and Europe. That same month, the virus entered California from United States troops returning from the Vietnam War . It reached Japan, Africa and South America in 1969. Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian province in China. A/Fujian (H3N2) human flu (from A/Fujian/411/2002(H3N2)-like flu virus strains) caused an unusually severe 2003–2004 flu season. This was due to a reassortment event that caused a minor clade to provide a haemagglutinin gene that later became part of the dominant strain in the 2002–2003 flu season. A/Fujian (H3N2) was made part of the trivalent influenza vaccine for the 2004–2005 flu season . The 2004–05 trivalent influenza vaccine for the United States contained:The vaccines produced for the 2005–2006 season used:The 2006–2007 influenza vaccine composition recommended by the World Health Organization on 15 February 2006 and the US FDA's Vaccines and Related Biological Products Advisory Committee on 17 February 2006 used: an A/New Caledonia/20/99 (H1N1)-like virus an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 strains) a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004 and B/Ohio/1/2005 strains which are of B/Victoria/2/87 lineage The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on 14 February 2007 was: "A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B." Many H3N2 viruses making people ill in this 2007–2008 flu season differ from the strains in the vaccine and may not be well covered by the vaccine strains. "The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved [notably] from the H3N2 strain in the vaccine—A/Wisconsin/67/2005." The composition of virus vaccines for use in the 2008–2009 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2008 was: As of May 30, 2009: "CDC has antigenically characterized 1,567 seasonal human influenza viruses [947 influenza A (H1), 162 influenza A (H3) and 458 influenza B viruses] collected by U.S. laboratories since October 1, 2008, and 84 novel influenza A (H1N1) viruses. All 947 influenza seasonal A (H1) viruses are related to the influenza A (H1N1) component of the 2008–09 influenza vaccine (A/Brisbane/59/2007). All 162 influenza A (H3N2) viruses are related to the A (H3N2) vaccine component (A/Brisbane/10/2007). All 84 novel influenza A (H1N1) viruses are related to the A/California/07/2009 (H1N1) reference virus selected by WHO as a potential candidate for novel influenza A (H1N1) vaccine. Influenza B viruses currently circulating can be divided into two distinct lineages represented by the B/Yamagata/16/88 and B/Victoria/02/87 viruses. Sixty-one influenza B viruses tested belong to the B/Yamagata lineage and are related to the vaccine strain (B/Florida/04/2006). The remaining 397 viruses belong to the B/Victoria lineage and are not related to the vaccine strain." The vaccines produced for the 2009–2010 season used: an A/Brisbane/59/2007(H1N1)-like virus an A/Brisbane/10/2007 (H3N2)-like virus a B/Brisbane 60/2008-like antigens A separate vaccine was available for pandemic H1N1 influenza using the A/California/7/2009-like pandemic H1N1 strain. The vaccines produced for the 2010–2011 season used: an A/California/7/2009-like (pandemic H1N1) an A/Perth/16/2009-like (H3N2)-like virus a B/Brisbane/60/2008-like antigens The vaccines produced for the 2011–2012 season used: an A/California/07/2009 (H1N1)-like virus an A/Victoria/210/2009 (an A/Perth/16/2009-like strain) (H3N2)-like virus a B/Brisbane/60/2008-like virus The vaccines produced for the Northern Hemisphere 2012–2013 season used: In January 2013, influenza activity continued to increase in the United States and most of the country experienced high levels of influenza-like-illness (ILI), according to CDC's latest FluView report. Reports of influenza-like-illness (ILI) are nearing what have been peak levels during moderately severe seasons, and CDC continues to recommend influenza vaccination and antiviral drug treatment when appropriate at this time. On January 9, 2013, the Boston Government declared a public health emergency for H3N2 influenza. The vaccines produced for the Northern Hemisphere 2014–2015 season used: A/California/7/2009 (H1N1)pdm09-like virus A/Texas/50/2012 (H3N2)-like virus B/Massachusetts/2/2012-like virus, Quadrivalent vaccines include a B/Brisbane/60/2008-like virus. The CDC announced that drift variants of the A (H3N2) virus strain from the 2012–2013 potentially foretold a severe flu season for 2014–2015. The vaccines produced for the Northern Hemisphere 2015–2016 season used: A/California/7/2009 (H1N1)pdm09-like virus A/Switzerland/9715293/2013 (H3N2)-like virus B/Phuket/3073/2013-like virus. (This is a B/Yamagata lineage virus) The "Split Virion" vaccine distributed in 2016 contained the following strains of inactivated virus: A/California/7/2009 (H1N1)pdm09 - like strain (A/California/7/2009, NYMC X-179A) A/Hong Kong/4801/2014 (H3N2) - like strain (A/Hong Kong/4801/2014, NYMC X-263B) B/Brisbane/60/2008 - like strain (B/Brisbane/60/2008, wild type) A/California/7/2009 (H1N1)pdm09-like virus, A/Hong Kong/4801/2014 (H3N2)-like virus B/Brisbane/60/2008-like virus (B/Victoria lineage) Quadrivalent influenza vaccine adds: B/Phuket/3073/2013-like strainA/Michigan/45/2015 (H1N1)pdm09-like virus A/Hong Kong/4801/2014 (H3N2) B/Brisbane/60/2008-like virus (B/Victoria lineage) Quadrivalent influenza vaccine adds B/Phuket/3073/2013-like[B/Yamagata lineage]Quadrivalent - A/Brisbane/02/2018 (H1N1)pdm09-like virus A/SouthAustralia/34/2019 (H3N2)-like virus B/Washington/02/2019-like virus [B/Victoria lineage] B/Phuket/3073/2013-like virus [B/Yamagata lineage]

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Pandemic influenza

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2009 swine flu pandemic timeline

This article covers the chronology of the 2009 novel influenza A ( H1N1 ) pandemic. Flag icons denote the first announcements of confirmed cases by the respective nation-states, their first deaths (and other major events such as their first intergenerational cases, cases of zoonosis , and the start of national vaccination campaigns), and relevant sessions and announcements of the World Health Organization (WHO), the European Union (and its agency the European Centre for Disease Prevention and Control ), and the U.S. Centers for Disease Control (CDC). Unless otherwise noted, references to terms like S-OIV, H1N1 and such, all refer to this new A(H1N1) strain and not to sundry other strains of H1N1 which are endemic in humans, birds and pigs.Take note that the date of the first confirmations of the disease or any event in a country may be before or after the date of the events in local time because of the International Dateline . Mexico In La Gloria, Veracruz 60% of the town's population is sickened by a respiratory illness of unknown provenance. The government of Mexico believes it to be caused by H3N2 influenza, though at least one patient in La Gloria tested positive for A/H1N1. Two babies died in the outbreak but both were buried without testing. United States In the ninth week of its routine influenza surveillance, the CDC reports on FluView that thirty-five states have reported widespread influenza activity, and 14 states have reported regional activity, but that although the rate of activity was high, that the proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold. United States The CDC reports on the 10th week of FluView that thirty states reported widespread influenza activity and 18 states reported regional activity. Mexico Earliest known onset of a case that is later to be confirmed as Swine-Origin Influenza A (H1N1) Virus Infection. United States CDC FluView, Week 11: Widespread influenza activity in twenty-four states; regional activity in 19. Influenza activity continues to decrease. United States Earliest known onset of a USA case later confirmed as swine flu, that of a nine-year-old girl residing in Imperial County, California . Thirteen states reported widespread influenza activity and 19 reported regional activity on the CDC's FluView, Week 12. United States A sample is collected from a nine-year-old female patient which is later confirmed to contain the novel virus strain (genetically sequenced as A/California/05/2009(H1N1)). United States Onset of illness for a ten-year-old boy residing in San Diego County, California ; his case is eventually the first to be confirmed as swine flu in the US. United States A nasopharyngeal swab is collected from a ten-year-old male patient in San Diego County, later confirmed as containing the novel virus and the first organism of that strain to be completely sequenced (A/California/04/2009(H1N1)). Mexico In La Gloria, Veracruz , a four-year-old boy falls ill at the end of the outbreak. Only his sample, which was eventually sent abroad, tested positive for A(H1N1). Veracruz officials state that there were no plans to exhume the bodies of two infants who died in the outbreak. United States CDC FluView, Week 13: Widespread influenza activity in four states, regional activity in 18. European Union The media monitoring website MedISys reports on a Mexican article about the epidemiological alert. Mexico Public health authorities begin investigating unusual cases of pneumonia . 400 people had reportedly sought treatment for pneumonia/ influenza-like illness (ILI) in La Gloria the preceding week. United States Biosurveillance firm Veratect reports the unusual respiratory illness in Mexico. Veratect publishes the alert "La Gloria: 'Strange' Respiratory Affects 60% of Local Population; Three Pediatric Deaths May be Associated with the Outbreak." United States CDC FluView, Week 14: Widespread influenza activity in one state; regional activity in 14. Mexico The General Directorate of Epidemiology (DGE) reports the outbreak of an ILI in a small community in Veracruz to the Pan American Health Organization ( PAHO ), which is the Regional Office of the World Health Organization ( WHO ). Furthermore, a 39-year-old woman dies of severe viral pneumonia in the city of San Luis Potosí ; this is later believed to be the earliest known fatality related to the outbreak. Mexico First death in Oaxaca due to what would later be identified as swine flu. United States The U.S. Centers for Disease Control (CDC) is advised of a ten-year-old boy with a respiratory illness in San Diego County, California. Test results revealed an Influenza A virus but were negative for standard human strains. The San Diego County Health Department is notified. United States The CDC receives its first sample from California (from the ten-year-old boy in San Diego County), and identifies the virus as a strain of swine influenza A(H1N1). Mexico Authorities notify the PAHO of the atypical pneumonia . United States Veratect publishes the alert "Atypical Pneumonia Cases Reported at Hospital" regarding the Oaxaca cases. Mexico A case of atypical pneumonia in Oaxaca prompts enhanced national surveillance. A field investigation is started. Mexico contacts Canada to request more specialized testing. United States The CDC receives a second sample from Southern California (taken from the nine-year-old girl in Imperial County), and again identifies the virus as a strain of swine influenza A(H1N1). The California Department of Public Health is notified. Mexico Mexico sends 14 mucus samples to the CDC and dispatches health teams hospitals to look for patients showing severe influenza- or pneumonia-like symptoms. United States CDC FluView, Week 15: "Nine states reported regional activity; 17 states reported local influenza activity; the District of Columbia and 22 states reported sporadic influenza activity; and two states reported no influenza activity. Seven human infections with swine influenza A (H1N1) virus have been confirmed." This is the first mention of A(H1N1) in FluView. United States Veratect advises the CDC of the Mexican events. The CDC is already investigating the California and Texas cases. United States The CDC alerts physicians to a similar novel strain of swine influenza A(H1N1) in two cases from Southern California in a Morbidity and Mortality Weekly Report Early Release on its website. Local investigations, including investigations in Texas, are already underway, and overall surveillance is enhanced. The Associated Press covers the alert, the first mention of the A(H1N1) outbreak in English-language news media. Canada Canada receives the samples from Mexico for testing. Mexico The Public Health Agency of Canada confirms Mexico cases of swine-origin influenza A (H1N1) virus (S-OIV) infection. Genetic sequence analysis reveals that the Mexican patients were infected with the same S-OIV strain detected in two California children. The PAHO is informed that a cluster in Mexico of severe respiratory illnesses has been laboratory-confirmed as S-OIV infection. The WHO issues its first Disease Outbreak Notice on the matter, confirming the infection of a number of people in Mexico and the United States by "Swine Influenza A/H1N1 viruses... not... previously detected in pigs or humans". Mexico The Minister of Health confirms the Mexican cases of human infection by swine influenza and states that it believes that some of these cases had resulted in death. Health authorities implement public health measures for all airport passengers and the vaccination of health care workers with seasonal influenza vaccine . United States The CDC tells a press conference that seven of the 14 Mexican samples contained the same virus strain as the known in California and Texas, and that indications suggested that containment in the USA was "not very likely". The novel strain had already been reported on the CDC's Morbidity and Mortality Weekly Report website. WHO Under the International Health Regulations (IHR), the Emergency Committee convenes for the first time since its establishment in 2007, resulting in the WHO Director-General declaring a formal "public health emergency of international concern," ( PHEIC ), the first ever. The PAHO Vaccination Week In The Americas starts. The 2009 Week was planned to emphasize the vaccination of entire families, and health worker immunization . United States First closure of an entire school district, the Schertz-Cibolo-Universal City Independent School District outside San Antonio, Texas . United States United States declares a Public Health Emergency. WHO The Emergency Committee meets for the second time. The WHO Director-General issues a statement that containment of the outbreak is not feasible, and elevates the pandemic alert from Phase 3 to Phase 4. European Union (EU) Health Commissioner advises Europeans not to travel to the United States or Mexico unless the need is urgent. This follows the first confirmed case in Spain. Canada First six cases confirmed, four in Nova Scotia and two in British Columbia. Mexico First seven confirmed deaths Spain First confirmed case of swine flu, in Almansa , and thus the first case in Europe; A(H1N1) has spread from the WHO Region of the Americas to the WHO European Region. ( ) United Kingdom First two confirmed cases, in Scotland. WHO Confirmed cases are now extant in four of six WHO regions (see map). As of 19:15 GMT seven countries have officially reported cases of swine influenza A(H1N1) infection. Canada Confirmed: two cases and another four in Alberta and Ontario , respectively. Israel First confirmed case in Israel and thus the WHO Eastern Mediterranean Region (color-coded yellow), the third region to be affected. New Zealand First three confirmed cases in New Zealand and thus the WHO Western Pacific Region (color-coded red), the fourth region to be affected. Spain The second confirmed case in Spain, in Valencia . WHO The Emergency Committee meets for the third time, and the WHO raises its pandemic alert level from Phase 4 to Phase 5, its second highest. As of 1800 GMT, nine countries have officially reported 148 cases of swine influenza A(H1N1) infection. ASEAN ASEAN officials are looking at coordinating measures to address the potential pandemic. EU Foreign Relations Commissioner Benita Ferrero-Waldner announces that the halt of all travel to Mexico and disinfecting all airports due to the global flu outbreak is being considered. Austria First confirmed case. Germany First three confirmed cases, two in Bavaria and one in Hamburg . Spain Eight more cases raises the total in Spain to 10, including the first human-to-human intergenerational transmission (in which the patient had not recently been to Mexico but was infected by another patient who had just visited Mexico, namely his girlfriend). This is the first intergenerational transmission to be documented in Europe. United States First death outside Mexico, a 23-month-old Mexican child hospitalized in Texas. Ninety-one confirmed cases in the US to date. South Africa First two cases reported within South Africa, by two women that travelled in Mexico weeks earlier. The cases were confirmed on 18 June 2009. Canada Confirmed: One more case in Toronto , and eight more cases in Nova Scotia , and Alberta bringing total to 28. Ireland First confirmed case. Netherlands First confirmed case, a three-year-old child. The child returned from Mexico to the Netherlands on April 27, 2009. The parents test negative for A(H1N1). Switzerland First confirmed case. United States Four cases are confirmed in an outbreak at the University of Delaware ; another 12 cases are deemed "probable". One of the confirmed cases is a baseball player, which results in the university cancelling sporting events, a concert by rapper Young Jeezy , and other school activities. United Kingdom Three further confirmed cases of swine flu, giving a total of eight confirmed cases. WHO As of 0600 GMT, 11 countries have officially reported 331 cases of influenza A(H1N1) infection. Canada 51 confirmed cases. Hong Kong Denmark First confirmed case (in Hvidovre). France First two confirmed cases. Mexico begins an unprecedented five-day shutdown to fight the spread of the flu. United Kingdom First and second case of human to human (or intergenerational) transmission within the UK confirmed. United States 155 confirmed cases, including two at George Washington University's Thurston Hall. WHO As of 0600 GMT 15 countries have officially reported 615 cases of influenza A(H1N1) infection. Canada The Canadian Food Inspection Agency confirms the first human-to-animal transmission of the virus after an Albertan returns from Mexico and infects a pig farm, the first known case of (reverse) zoonosis . China suspends flights from Mexico. South Korea First confirmed case. United States There are more than 430 school closures in 18 states. CDC FluView Week 17: Widespread activity in seven states, regional activity in 12. WHO As of 0600 GMT, 17 countries have officially reported 787 cases of (A)H1N1. Arab League Health Ministers meet in Riyadh, to discuss human and technical support to be deployed in any Arab affected place. Canada 101 confirmed cases after seven cases in British Columbia , three in Alberta , two in Nova Scotia and Ontario , and one in Quebec were confirmed. Colombia First confirmed case in South America . WHO As of 06:00 GMT, 20 countries have officially reported 985 cases of influenza A (H1N1) infection. Canada A girl from Edmonton , Alberta was diagnosed with a severe case of the H1N1 virus. WHO As of 06:00 GMT, 21 countries have officially reported 1,124 cases of influenza A (H1N1) infection. United States WHO As of 06:00 GMT, 22 countries have officially reported 1,516 cases of influenza A (H1N1) infection. ASEAN A special regional summit to fight possible swine flu pandemic was held in Bangkok and was attended by senior ASEAN health officials along with those from China, Japan and South Korea. Guatemala First confirmed case, and the first in Central America. Poland First confirmed case. Sweden First confirmed case. WHO As of 18:00 GMT, 24 countries have officially reported 2,371 cases of influenza A (H1N1) infection. Argentina First confirmed case. Brazil First four confirmed cases. Canada Reports suggest that an elderly woman who had swine flu has died in northern Alberta, marking the first death in Canada related to swine flu. Furthermore, an unusual case of zoonosis occurred when a swine flu inspector in improper gear caught the virus from an infected pig. Netherlands Second case confirmed, a 53-year-old woman who had recently travelled to Mexico. USA The New England Journal of Medicine establishes its H1N1 Influenza Center on its website. WHO As of 16:00 GMT, 25 countries have officially reported 2,500 cases of influenza A (H1N1) infection. Japan First three confirmed cases. Panama First confirmed case. WHO As of 06:00 GMT, 29 countries have officially reported 3,440 cases of influenza A(H1N1) infection. Australia First confirmed case. Brazil Two cases confirmed, one of which is thought to be the first case of human-to-human infection in Brazil. Costa Rica First confirmed death, and also the first death outside of North America. Three other confirmed cases, all children, were contaminated by the patient who died. Japan 4th confirmed case, a schoolmate of the first three cases. Norway First two confirmed cases. United States Third confirmed death, a Washington man with underlying heart disease. Also, the USA passes Mexico in the number of confirmed cases of infection, 1693 to 1364, thus becoming the nation-state with the most laboratory-confirmed cases of infection; Canada is third with 242 cases. CDC FluView Week 18: Widespread influenza activity in eight states, regional activity in 14. WHO As of 07:30 GMT, 29 countries have officially reported 4,379 cases of influenza A(H1N1) infection. China First confirmed case. WHO As of 06:00 GMT, 30 countries have officially reported 4,694 cases of influenza A(H1N1) infection. WHO As of 06:00 GMT, 30 countries have officially reported 5,251 cases of influenza A(H1N1) infection. Canada The first case in Yukon Territory is confirmed. Spain 100 cases confirmed. WHO As of 06:00 GMT, 13 May 2009, 33 countries have officially reported 5,728 cases of influenza A(H1N1) infection. Belgium First confirmed case. Panama 10 more cases confirmed today. Total: 39. WHO As of 06:00 GMT, 33 countries have officially reported 6,497 cases of influenza A(H1N1) infection. Belgium Second confirmed case. Colombia First domestic infections with three cases confirmed. Total: 10. WHO As of 06:00 GMT, 34 countries have officially reported 7,520 cases of influenza A(H1N1) infection. USA Fourth and fifth deaths confirmed, that of an Arizona woman suffering from a lung condition and a Texas man in Corpus Christi, respectively. Malaysia First confirmed case. Malaysia is the 37th country to be affected by the virus. Panama Four new cases confirmed today. Total: 43, 23 of whom are male and 20 of whom are female. 20 of the cases are under 15 years old. WHO As of 06:00 GMT 36 countries have officially reported 8,451 cases of influenza A(H1N1) infection. India First case confirmed, in Hyderabad. This marks the arrival of A(H1N1) in the fifth of the WHO's six regions, the South-East Asia Region. Japan First domestic infection confirmed, in Kobe , a male high school student with no history of travel abroad. The Kobe Festival , planned for May 16 and 17, is cancelled. Malaysia Second confirmed case. The first patient is now showing significant improvement from the treatment. Panama 11 new confirmed cases. 54 total. Turkey First confirmed case, that of an American tourist flying from the United States via Amsterdam, discovered at Istanbul's Atatürk International Airport. United States CDC FluView Week 19: Widespread influenza activity in five states, regional activity in 13. WHO As of 06:00 GMT 37 countries have officially reported 8,480 cases of influenza A(H1N1) infection. Panama With 54 confirmed cases, Panama occupies second place, along with Canada, for the number of cases per country. WHO As of 06:00 GMT, 40 countries have officially reported 8,829 cases of influenza A(H1N1) infection, including 74 deaths. ECDC The European Centre for Disease Control releases its early findings on H1N1's pandemic potential. Japan reports 96 confirmed cases; it now ranks fourth in the world in the number of infections. Thousands of schools in 21 cities in the Hyogo and Osaka prefectures are temporarily closed. USA The sixth death in the US, and the first in New York—that of an assistant principal. WHO As of 06:00 GMT, 40 countries have officially reported 9,830 cases of influenza A(H1N1) infection, including 79 deaths. United States Seventh confirmed death, that of a 44-year-old Missouri man. Japan 191 confirmed cases; Hyogo Prefecture has the most at 111. Norway One more case confirmed today. Total: three. Paraguay confirmed its first case and became the 43rd affected country. Taiwan confirmed its first case and becomes the 44th affected country. WHO As of 06:00 GMT, 40 countries have officially reported 10,243 cases of influenza A(H1N1) infection, including 80 deaths. United States A patient dies in Arizona, and a 22-year-old man dies in Utah, the nation's eighth and ninth H1N1 fatalities. Roughly half of the influenza viruses detected by the CDC's routine influenza surveillance systems are now that of novel A(H1N1). An unusual number of outbreaks in schools is reported. Japan 236 confirmed cases, including the first case in Shiga Prefecture , and the cities of Hachiōji and Kawasaki in the Greater Tokyo Area . Two female high school students from Tokyo who had recently attended a Model United Nations conference in New York are presumed to have become infected abroad. Norway 1 more case confirmed today. Total: 4. WHO As of 06:00 GMT, 41 countries have officially reported 11,034 cases of influenza A(H1N1) infection, including 85 deaths. Japan 279 confirmed cases; more than 4,800 schools are closed in the Kobe region. WHO As of 06:00 GMT, 42 countries have officially reported 11,168 cases of influenza A(H1N1) infection, including 86 deaths. Japan 317 confirmed, including first confirmed in Saitama Prefecture . Third confirmed in Tokyo, a 25-year-old man who visited Osaka from May 14-20th. Philippines First case confirmed. WHO As of 06:00 GMT, 43 countries have officially reported 12,022 cases of influenza A(H1N1) infection, including 86 deaths. Iceland First confirmed case. 4 more cases suspected. United States CDC FluView Week 20: Widespread influenza activity in four states; regional activity in 11. Australia Two more confirmed cases, which now brings the national toll to 16. Kuwait First confirmed cases, that of 18 U.S. soldiers. WHO As of 06:00 GMT, 46 countries have officially reported 12,515 cases of influenza A(H1N1) infection, including 91 deaths. Australia 22 Confirmed Cases. Ireland Second confirmed case. WHO As of 06:00 GMT, 46 countries have officially reported 12,954 cases of influenza A(H1N1) infection, including 92 deaths. Argentina 14 Confirmed Cases. Total: 19. Australia 61 confirmed cases. Puerto Rico First confirmed case. WHO As of 06:00 GMT, 48 countries have officially reported 13,398 cases of influenza A(H1N1) infection, including 95 deaths Argentina 37 cases confirmed. Dominican Republic First two confirmed cases. Greece confirmed two more cases. Romania First confirmed case. Singapore First confirmed case. A 22-year-old woman picked up the virus after visiting New York. United Kingdom Two new cases confirmed. Total: 186. Uruguay confirmed its first two cases. Australia 147 confirmed cases. Singapore Three more cases confirmed. Total confirmed cases now stands at four. United Kingdom Seventeen more confirmed cases. Total: 203. Bolivia First 2 cases confirmed. Venezuela First confirmed case. WHO As of 06:00 GMT, 53 countries have officially reported 15,510 cases of influenza A(H1N1) infection, including 99 deaths United Kingdom 14 confirmed cases. Total: 217. Norway One new confirmed case. Total: 5. Hungary First confirmed case Uruguay 4 new confirmed cases. Total: 6. Greece Another one case confirmed. Total: 4. Estonia First confirmed case. United States CDC FluView Week 21: Widespread influenza activity in five states, regional activity in 10. Dominican Republic Nine more cases confirmed, for a total of 11 cases nationwide. WHO As of 06:00 GMT, 62 countries have officially reported 17,410 cases of influenza A(H1N1) infection, including 115 deaths. Bulgaria First confirmed case. Bermuda First case confirmed. Egypt First case confirmed. Luxembourg First case confirmed. Nicaragua First case confirmed. WHO As of 06:00 GMT, 3 June 2009, 66 countries have officially reported 19,273 cases of influenza A(H1N1) infection, including 117 deaths. Saudi Arabia First confirmed case. Barbados First confirmed case. Malaysia Three more cases confirmed. One of the patients is a 23-year-old student returned from the United States. Another two patients are German tourists who arrived in Singapore after having gone to Malaysia for holiday. Total: 5. Trinidad and Tobago First confirmed case. WHO As of 06:00 GMT, 69 countries have officially reported 21,940 cases of influenza A(H1N1) infection, including 125 deaths. Australia 1006 cases confirmed. Cayman Islands First case confirmed. Dominican Republic First fatality, a 17-year-old pregnant girl. Total number of confirmed cases rises to 44. Ukraine First confirmed case. Malaysia One more case confirmed. Total: 7. United States CDC FluView Week 22: Widespread influenza activity in eight states, regional activity in nine. "Approximately 89% of all influenza viruses being reported to CDC were novel influenza A (H1N1) viruses." Chile Second death confirmed. Martinique First case confirmed. New Zealand Authorities have confirmed that a man traveling from North America has Influenza A(H1N1). Total: 14. WHO As of 06:00 GMT, 73 countries have officially reported 25,288 cases of influenza A(H1N1) infection, including 139 deaths. Dominica First confirmed case. New Zealand Three more confirmed cases, two of which were from international flights. Total: 17. WHO As of 06:00 GMT, 74 countries have officially reported 27,737 cases of influenza A(H1N1) infection, including 141 deaths. Colombia First death confirmed. French Polynesia First confirmed case in the islands. Guatemala First death confirmed. The WHO raises its Pandemic Alert Level to Phase 6, citing significant transmission of the virus. Australia 1263 cases nationally, with more than 1000 cases in the State of Victoria alone. British Virgin Islands First case confirmed in the islands. Cuba Sixth case on the island, and that of the first citizen. Palestinian Territories First case confirmed in the West Bank. WHO As of 07:00 GMT, 12 June 2009, 74 countries have officially reported 29,669 cases of Influenza A (H1N1) infections, including 145 deaths. Morocco First case confirmed. Isle of Man First case confirmed. Bolivia First two domestic infections. Total: 7. Malaysia One more confirmed case. Total: 12. United States Widespread influenza activity in eleven states, regional activity in six. "Over 98% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." Malaysia Five more cases of H1N1 confirmed. Total: 17. United Kingdom First death confirmed. Sri Lanka First confirmed case. Monaco First confirmed case. Malaysia Four more cases of H1N1 confirmed. One domestic infection confirmed. Total: 23. Antigua and Barbuda First confirmed case. Bangladesh First confirmed case. Ethiopia First two cases confirmed. Slovenia First confirmed case. Philippines First death in Asia confirmed. H1N1 deaths now confirmed in 3 of 6 WHO regions. Iraq First seven cases confirmed. Japan 52 more cases confirmed. Total: 944. Serbia First confirmed case. United States CDC FluView Week 24: Widespread influenza activity in twelve states, regional activity in seven. "Over 99% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." United States CDC FluView Week 25: Widespread influenza activity in ten states, regional in 11 states. Bosnia and Herzegovina First case confirmed. Denmark First case of Oseltamivir (Tamiflu) resistance found. Confirmed by David Reddy, Roche's pandemic taskforce leader. Kenya First confirmed case. Mauritius First case confirmed. Nepal First three confirmed cases. South Africa South Africa National Health Department confirm community outbreak, with 7 new confirmed cases. The total of confirmed cases grew to 12640 within South Africa over the next few months. [ citation needed ] Guam First case confirmed. Australia First confirmed death in NSW . National total: 10. Japan Second case found with mutation resulting in Oseltamivir (Tamiflu) resistance. United States CDC FluView Week 26: Widespread influenza activity in nine states, regional influenza activity in 12. "Over 97% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Portugal First human-to-human transmission. Total: 38. Syria First case confirmed. Peru First two deaths confirmed. WHO 429 deaths worldwide are reported. Belize First five cases confirmed. Tanzania First case confirmed. United States CDC FluView Week 27: Widespread influenza activity in nine states, regional activity in 12. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Colombia 6th death case confirmed out of 165 infected Malaysia 39 more cases confirmed. Total: 710. United Kingdom Another 2 deaths confirmed. Total Deaths: 17. Brazil One more death confirmed. Total Deaths: 3. Ecuador Third death confirmed. Total deaths: 3. Brazil Fourth death confirmed. Malaysia 32 more cases confirmed. Total: 804 New Zealand Two more deaths confirmed. Total deaths 9. Total confirmed cases: 1,984. Singapore First flu-related death confirmed, that of a 49-year-old man with heart problems. Sudan First two confirmed cases of H1N1 detected, from flights which had arrived from the U.K. Hawaii First death, that of a sexagenarian with underlying health problems. United States CDC FluView Week 28: Widespread influenza activity in seven states, regional activity in 13. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Venezuela First death confirmed, that of an 11-year-old girl. Singapore First death with H1N1 involvement confirmed, that of a 49-year-old male who also suffered from diabetes, hypertension and high cholesterol, from a heart attack caused by severe pneumonia. Egypt First death confirmed. Georgia First case confirmed. Albania First case confirmed. Guam First death confirmed. Namibia First two H1N1 cases confirmed. Canada The fourth case of mutation in the world from Tamiflu has been found in a 60-year-old man from Quebec , Canada . Federated States of Micronesia First case confirmed, that of a 27-year-old male. Northern Mariana Islands First two cases of H1N1 confirmed. Hungary First death confirmed, that of a man with underlying heart and lung disease. Tonga First death confirmed. The WHO ceases the tracking of cumulative individual cases. Arab League Health Ministers hold a summit after the death of a pilgrim who had returned from the Hajj . New regulations were promulgated for the Hajj: anyone younger than 12 or older than 65 or who have "chronic health problems" shall not be allowed to undertake the pilgrimage to Mecca. Bhutan First case confirmed. Malaysia First flu-related death confirmed, that of an obese 30-year-old male. Canada Nova Scotia reports its first H1N1 death. Cayman Islands First death reported, that of a man with underlying medical conditions. Indonesia First H1N1 death confirmed, that of a 6-year-old girl suffering from severe pneumonia. United States It is reported that thousands of Americans are being recruited for H1N1 vaccine testing at several research centers across the country. CDC FluView Week 29: Widespread influenza activity in four states, regional activity in eight. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Norway An international 4H youth camp with 1,700 participants from fifteen nations is shut down after fifty Norwegian participants catch H1N1. WHO 816 deaths worldwide are reported. Germany Germany's federal infectious disease center, the Robert Koch Institute , states there were 3,810 confirmed cases of H1N1 in the country; nearly all of the cases are mild. Israel First death confirmed, that of a 35-year-old man from Eilat. Kosovo First case confirmed. Saint Kitts and Nevis First death reported, that of a 28-year-old woman. Saudi Arabia First death confirmed. Japan Third case of Oseltamivir (Tamiflu) resistance. Thailand In the first reported case of vertical transmission of A(H1N1), a baby is born infected. Swaziland First case confirmed. United Kingdom The NHS is not ready for a second wave of swine flu cases expected this autumn, a House of Lords committee has stated. It warned hospitals do not have enough intensive care beds to cope, and furthermore predicted that the recently established A(H1N1) flu helpline could be overwhelmed with calls. United States The U.S. military wants to establish regional teams of military personnel to assist civilian authorities in the event of a significant outbreak of the H1N1 virus this fall, according to Defense Department officials. Azerbaijan First two cases of A(H1N1) confirmed, those of people who had been on holiday in France and the U.K., respectively. Belgium First death confirmed, that of a 34-year-old woman. France First death confirmed, a 14-year-old girl in Brest . Gabon First case confirmed. Lebanon First death confirmed, that of a 30-year-old male. Moldova First case confirmed. Saudi Arabia Second H1N1 death confirmed, that a 28-year-old Indonesian woman. Taiwan First death confirmed, that of a 39-year-old man. WHO 1,154 deaths worldwide are reported. France The cruise ship Voyager of the Seas , which had reported dozens of cases of H1N1 flu amongst its 5,000 passengers and crew, docks in France. Australia First case of reverse zoonosis confirmed in a piggery in Dunedoo . United States CDC FluView Week 30: Widespread influenza activity in four states, regional activity in 11. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." South Africa First confirmed death in South Africa. Total number of deaths at end of epidemic 93. [ citation needed ] India First death confirmed. Netherlands First death confirmed, that of a 17-year-old male. Solomon Islands First case confirmed. WHO 1,462 deaths worldwide are reported. United States CDC FluView Week 31: Widespread influenza activity in four states, regional activity in 10. Costa Rica President Óscar Arias is confirmed to have swine flu, the first head of state known to have been infected. WHO 1,799 deaths worldwide are reported. Madagascar First case confirmed. Democratic Republic of the Congo First H1N1 case confirmed. United States CDC FluView Week 32: Widespread influenza activity in two states, regional activity in eight. Malaysia Two more deaths confirmed. Total: 64 deaths. Malta First death confirmed. Malaysia Three more deaths confirmed. Total: 67 deaths. Belarus First H1N1 case confirmed. [ citation needed ] Kuwait First death confirmed. Malaysia One more death confirmed. Total: 68 deaths. The unusually high reported death rate, four times the global average, is investigated by the WHO. Netherlands Second death confirmed, that of a 58-year-old male. Chile H1N1 is found in turkeys on farms in Chile near the port city of Valparaiso in a unique zoonosis cluster. Germany 13,740 A(H1N1) cases confirmed. Oman First death confirmed. United Arab Emirates First death confirmed. United Kingdom First death confirmed in Northern Ireland, that of woman with underlying health conditions. New Caledonia First death confirmed. United States CDC FluView Week 33: Widespread influenza activity in two states, regional activity in 13. Activity appears to be increasing in the Southeast. WHO At least 2,185 deaths worldwide are reported. Greece First death confirmed. Germany 14,325 H1N1 cases confirmed. Kyrgyzstan First two cases confirmed, that of a husband and wife; the man had recently traveled to Dubai. Malaysia One more death confirmed. Total: 69 deaths. Malaysia One more death confirmed. Total: 70 deaths. Angola First case confirmed. Germany 14,940 H1N1 cases confirmed. Iran First death confirmed [ citation needed ] Malaysia One more death confirmed. Total: 71 deaths. Syria First death confirmed. UN ; Chile The United Nations issues a warning regarding the discovery of H1N1-infected turkeys on farms in Chile, an unusual case of zoonosis which raises concerns about possible increased genetic reassortment of the virus. WHO Most countries in the Southern Hemisphere (represented by Chile, Argentina, New Zealand, and Australia) appear to have passed their peak of influenza activity and returned to baseline activity. ECDC Based partially on data from the Southern Hemisphere, the ECDC forecasts a first wave of infections in autumn and winter which stresses hospitals in particular; it is noted, however, that "the overall interruption of essential services in (well-prepared) countries has been manageable". Germany 15,567 H1N1 cases confirmed. Bangladesh First death confirmed. Brazil 602 H1N1 deaths confirmed, the highest number of any nation-state to date. United States CDC FluView Week 34: Influenza activity, which had been largely stable or decreasing in prior weeks, increases in the U.S. "Six states and Puerto Rico reported geographically widespread influenza activity, 13 states reported regional influenza activity, 10 states and the District of Columbia reported local influenza activity, 19 states reported sporadic influenza activity, two states reported no influenza activity, and Guam and the U.S. Virgin Islands did not report." Furthermore, Region IV, i.e. the Southeast, reports increased out-patient ILI above its regional baseline. WHO At least 2,837 deaths worldwide are reported. Colombia President Álvaro Uribe is confirmed to have swine flu, the second Head of state known to have been infected. Djibouti First seven cases confirmed. United Arab Emirates Second death confirmed, that of a thirty-year-old Pakistani expatriate who died following Caesarian section . Argentina The most H1N1 deaths per capita . Bahrain First death confirmed, a South East Asian woman in her thirties with underyling medical conditions. Sweden First death confirmed. Macau First death confirmed. Portugal 5,123 cases officially confirmed Malaysia One more death confirmed. Total: 73 deaths. Norway First death confirmed. United States The CDC in its Morbidity and Mortality Weekly Report notes that 67% of thirty-six children who have died from H1N1 early in the epidemic had at least one serious chronic medical condition, with neurodevelopmental conditions such as developmental delay, epilepsy, and cerebral palsy being especially prominent. Roughly one in thirteen deaths have been of school-age children. More than 80% of the children who died were five or older, in contrast with the seasonal flu baseline of half or more of the influenza fatalities being four or younger. Italy First death confirmed. United States CDC FluView Week 35: Influenza increases in the U.S. with widespread influenza activity in 11 states and regional activity in 13; the proportion of outpatient visits for influenza-like illness (ILI) is above the national baseline, with four out of ten HHS Surveillance Regions reporting ILI above region-specific baselines. "97% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,205 deaths worldwide are reported. Ecuador Ecuador's chief of presidential security, Col. John Merino, dies of H1N1 flu after twenty-eight days at Quito Military Hospital. Faroe Islands First 44 cases confirmed. Namibia First death confirmed, that of a 37-year-old businessman who had fallen ill in Angola. Suriname First death confirmed. Madagascar First death confirmed. USA An outbreak is confirmed at the gaming convention PAX in Seattle, Washington. Malawi First case confirmed. Australia First case of Oseltamivir (Tamiflu) resistance found. United States CDC FluView Week 36: Influenza activity continues to increase with widespread influenza activity in twenty-one states, regional influenza activity in nine. Seven of ten HHS Surveillance Regions report ILI activity above region-specific baselines. "99% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,486 deaths worldwide are reported. Mozambique First death confirmed, that of a 29-year-old female with an unspecified chronic illness. Malta Third death confirmed. Netherlands The third and fourth deaths are confirmed, that of a 52-year-old man and an 85-year-old woman, respectively, both of whom had underlying medical conditions. United Kingdom Health Minister Andy Burnham states that the second peak of swine flu has started as 5,000 people contracted the virus this week, compared to 3,000 the week before. Martinique First death confirmed, that of an 18-month-old girl. Malaysia One more death confirmed. Total: 77 deaths. United States CDC FluView Week 37: Widespread influenza activity in twenty-six states, regional activity in 11. All of the HHS ILI regions report elevated levels of influenza activity above their region-specific baselines except for Region I (New England). WHO Over 3,917 deaths worldwide are reported. China A national vaccination campaign begins in China, making it the first country to issue the H1N1 vaccine. United States The U.S. government orders a total of 251 million doses of H1N1 vaccine from manufacturers, up from the long-planned total of 195 million. Portugal The first death confirmed, that of a Portuguese man living in France. Germany First death confirmed, that of a 36-year-old woman who died of a so-called superinfection which included H1N1. United States Forty-two schools are closed in eight states as the second wave of the pandemic begins in early autumn. United States CDC FluView Week 38: Widespread influenza activity in twenty-seven states, regional activity in 18. WHO At least 4,108 deaths worldwide are reported. United States The second wave of the H1N1 pandemic begins to stress hospitals in the U.S. and prompts some school closures. Cambodia First death confirmed, in Phnom Penh. Ireland First case of reverse zoonosis in pigs. Australia Mass vaccination drive begins, the second in the world. Bulgaria First death confirmed. China Sinovac Biotech Ltd., the first company worldwide to complete clinical trials for a vaccine, receives an order for an additional 3 million doses of H1N1 vaccine from the PRC government, making for a total of 6.3 million doses. United States 46 states and Washington, D.C. begin ordering what becomes by the next day a cumulative total of 1,378,200 doses of the nasal-spray Live Attenuated Influenza Vaccine ( LAIV ) for H1N1. United States CDC FluView Week 39: The proportion of deaths attributed to pneumonia and influenza (P&I) reaches the epidemic threshold with eight out of ten HHS ILI regions reporting region-specific ILI activity above region-specific baseline levels. Widespread influenza activity in thirty-seven states, regional activity in 11. WHO At least 4,525 deaths worldwide are reported. Tajikistan First case confirmed. United States The CDC's 2009–10 influenza season officially begins. United Nations Rich countries should make more vaccines available to poorer nations where the H1N1 virus is starting to hit, United Nations health officials said. They said increased readiness for swine flu was needed in developing countries with weaker medical systems and with large, young populations, who are most vulnerable to the disease. Some countries, such as the United States, Brazil and France, have agreed to make 10 percent of their national vaccine stockpile available to developing countries. Manufacturers have also donated about 150 million doses of vaccine. China First death confirmed, in Lhasa , Tibet . Tanzania First death confirmed. Yemen Tamiflu resistance found. Cuba First deaths confirmed, that of three pregnant women. United States CDC FluView Week 40: The proportion of deaths attributed to pneumonia and influenza (P&I) is officially above the epidemic threshold. Moreover, for the first time all 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-one states, and regional activity in eight, with only one state—Hawaii—reporting local influenza activity. WHO At least 4,735 deaths worldwide are reported. Norway first case of reverse zoonosis detected in Nord-Trøndelag . Rwanda First cases confirmed. São Tomé and Príncipe First cases confirmed. Sweden Mass vaccination begins. Vietnam Three cases of Tamiflu resistance (which developed during hospital treatment) are confirmed. The resistant strains were apparently not transmitted, and all three patients survived. Mongolia First cases confirmed. India Six more deaths confirmed. Total: 405 deaths. Trinidad and Tobago First death confirmed. United Kingdom The death toll passes 100. Total confirmed deaths: 106. The NHS confirms that second wave of swine flu has begun, with cases in Wales and Northern Ireland being especially high. The Minister of Health confirms that there were 27,000 cases in the last week in England alone, up from 14,000 the week before. The Minister of Health also announced that 415,000 H1N1 vaccinations shall take place on the week beginging 21 October, then 5,000,000 more vaccinations the week after. 20% of all hospitalized cases are now critical, up from 12% the week before. The government believes it can get 50,000,000 Britons vaccinated before Christmas. United States An initial shortfall of swine flu vaccine is predicted shortly after the proportion of deaths attributed to pneumonia and influenza goes above the epidemic threshold in some states, with flu activity widespread in 41 states. It is also announced that the number cases, hospitalizations and deaths are unprecedented for this time of year, with flu-like illnesses accounting for 6.1% of all doctor visits, itself an unusually high number. WHO At least 4,999 deaths worldwide are reported. China Second death confirmed, in the northwestern province of Qinghai . United States CDC FluView Week 41: All 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-six states, regional activity in three. United States H1N1 is confirmed in a nasal mucus sample taken from a show hog at the Minnesota State Fair in the first case of zoonosis in the country. India Two more deaths confirmed. Total: 415 deaths. Japan Mass vaccinations begin. Canada H1N1-infected turkeys are confirmed in Ontario, the second such case of zoonosis reported in the world. Iceland First death confirmed. United States In a unique case of zoonosis, a pet ferret in Oregon is confirmed to be infected with H1N1. Canada A turkey farm in Ontario province has been confirmed infected with A/H1N1 flu, making Canada the second country to report such infection after Chile, health officials confirmed Japan Ten H1N1-infected pigs are discovered in a swine herd in Osaka Prefecture, the first reported case of zoonosis in Asia. UK H1N1 vaccinations begin nationwide, with 14,000,000 high-priority people with conditions such as asthma to be vaccinated initially, then eventually up to 51,000,000 other Britons. Serbia First death confirmed. Czech Republic First death confirmed. Iraq Fears over the H1N1 virus prompts nearly 2,500 school closures. Germany Third H1N1 death confirmed. Mongolia First death confirmed. Netherlands Two new deaths reported, that of a 14-year-old girl and 40-year-old man. Total deaths: 6. United States President Barack Obama declares a national emergency , stating "The potential exists for the pandemic to overburden health care resources in some localities." United States Various public health departments across the country run out of the H1N1 vaccine, due to the shortfall of 10 million doses as the national vaccination campaign gets underway in earnest; 40 million doses had initially been projected. According to the CDC's FluView Week 42, influenza activity is widespread in 48 states, with regional activity in just two: Hawaii and South Carolina. WHO At least 5,712 deaths worldwide are reported. China Another death confirmed, in the northwestern province of Xinjiang . Oman Mass vaccinations begin. Canada Canada's H1N1 vaccination campaign begins. Russia First two deaths confirmed, in the far eastern city of Chita . Iceland First case of reverse zoonosis detected in pigs. Portugal A ten-year-old dies 48 hours after contracting the flu. Afghanistan First death confirmed. Nigeria First case confirmed. Republic of Congo First case confirmed. ECDC The European Centre for Disease Control reports a total of 302 fatal cases in Europe to date; all of the 27 EU and the four EFTA countries are reporting cases of pandemic (H1N1) 2009 influenza. Ukraine First death confirmed. Meanwhile, Ukrainian Prime Minister Yulia Tymoshenko ordered a massive and for Ukraine unprecedented disease-control programme to go into effect immediately in an attempt to prevent the spread of the disease. A 'full quarantine' will be imposed in seven provinces of Western Ukraine , with police monitoring the entrance and exit of all persons. It will block those lacking justification for travel Croatia First death confirmed. United States According to the CDC's FluView Week 43, influenza activity is widespread in 48 states, with regional activity in two: Hawaii and Mississippi. Afghanistan Schools are closed for three weeks after the first H1N1 death is recorded. Kuwait Mass vaccinations begin. Morocco Mass vaccinations begin. Turkey Mass vaccinations begin. WHO At least 6,071 deaths worldwide are reported. Austria First death confirmed. Belarus First death confirmed. Egypt Mass vaccinations begin. Qatar Mass vaccinations begin. Slovenia First death confirmed. US The USDA reports the first H1N1 zoonosis in commercial swine, in a herd in Indiana. Netherlands First case of Oseltamivir (Tamiflu) resistance found. United States The first case in the world of H1N1 zoonosis in a cat is confirmed, in Iowa. San Marino First case confirmed. Bulgaria A nationwide epidemic is declared. Hong Kong Reverse zoonosis is detected in two slaughtered pigs. Bahrain Mass vaccinations begin. Belgium Mass vaccination begins. Saudi Arabia Mass vaccinations begin. United States CDC FluView Week 44: Widespread influenza activity in forty-six state, regional activity in four. "The proportion of outpatient visits for influenza-like illness (ILI) was 6.7% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Pakistan First death confirmed. Sri Lanka First death confirmed. Latvia First death confirmed. United Arab Emirates Mass vaccinations begin. Greenland First case confirmed. Burundi First case confirmed. Armenia First two cases confirmed. France Mass vaccination drive begins. WHO In its 74th update, the WHO reports early signs that the early flu season has peaked in North America, even as the pandemic intensifies across much of Europe and Central and Eastern Asia. Bulgaria Health authorities confirm more than 12 people have died from H1N1 within a week; the latest victim is a 28-year-old man who died from respiratory failure. Cyprus First death confirmed. Kosovo First death confirmed. Poland First death confirmed. United States CDC FluView Week 45: Widespread influenza activity in forty-three states, regional activity in seven. "The proportion of outpatient visits for influenza-like illness (ILI) was 5.5% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Tunisia First confirmed deaths. Somalia First case confirmed. Bosnia & Herzegovina First death confirmed. North Korea First case confirmed. Morocco First confirmed deaths. Cyprus Mass vaccinations begin. Hungary National epidemic declared. Lithuania First death confirmed. Macedonia First death confirmed. United States First feline death confirmed, in the state of Oregon. Maldives First death confirmed. Denmark First death confirmed. Jordan Mass vaccinations begin. Norway A potentially significant mutation is found in specimens taken of the H1N1 virus taken from two fatalities; a third victim was seriously ill. UK The first person-to-person transmission of Tamiflu-resistant H1N1 in the world is confirmed at the University Hospital of Wales in Cardiff . Five patients are so infected, with three apparently having been infected in hospital in a case of iatrogenic transmission. US An iatrogenic Tamiflu-resistant cluster is reported at Duke University Medical Center in North Carolina, with four severely ill cancer patients infected, the largest cluster in the U.S. More than fifty resistant cases have been reported in the world since April. United States CDC FluView Week 46: Widespread influenza activity in thirty-two states, regional activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 4.3% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels. Romania First death confirmed, that of a 43-year-old man with obesity, high blood pressure, and diabetes. United States First double infection case confirmed, in a pediatrician in West Virginia. [ citation needed ] Montserrat First case confirmed. WHO H1N1 mutations have led to roughly 75 people worldwide developing Tamiflu resistance. Furthermore, the separate D222G or D225G mutation which helps the virus to reach deep into the lungs has been reported in cases both severe and mild in Norway, Ukraine, Brazil, China, Japan, Mexico and the United States. France The H1N1 mutation first detected in Norway causes two deaths in separate French cities. South Korea First double infection case confirmed, in a two-year-old girl. China Two cases in dogs are confirmed, the first instance of canine zoonosis in the world. Indonesia First case in pigs is confirmed, in southwest Sulawesi. United States CDC FluView Week 47: Widespread influenza activity, in Twenty-five states, regional influenza activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 3.7% which is above the national baseline of 2.3%. Eight of the 10 regions reported ILI at or above region-specific baseline levels. Regions 6 and 10 reported ILI below their region specific baselines." United States The CDC states that H1N1 may have peaked as the number of states reporting widespread influenza dropped from 43 the previous week to 32 this week. Furthermore, influenza-like illness now account for 4.3% of doctor visits, down from 8% four weeks ago (on average, influenza accounts for 2.5% of doctor visits). The proportion of deaths attributed to pneumonia and influenza continues to be higher than expected for this time of year, however. This proportion has remained elevated for eight weeks now. Finland First case of reverse zoonosis in pigs. Libya First death confirmed. Saudi Arabia Only five deaths and 73 cases are reported from the hajj . United Kingdom First case of reverse zoonosis in pigs is discovered, in Norfolk . US CDC FluView Week 48: Widespread flu activity in 14 states, regional activity in 25. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the tenth consecutive week. The proportion of outpatient visits for influenza-like illness (ILI) was 2.7% which is above the national baseline of 2.3%." Gaza Strip First five cases are confirmed in the blockaded Gaza Strip . Japan 100 fatalities confirmed. United States With one in six Americans infected, or 15% of the country, nearly 10,000 have died to date, including 1,100 children and 7,500 younger adults. More than 200,000 Americans had been hospitalized to date — roughly the same number who are so affected by the regular seasonal flu variant in an entire year. Furthermore, with 12 million additional doses of H1N1 vaccine being released this week, several states begin to distribute the vaccine to the general public. North Korea First deaths are confirmed, according to newsletters released by the Seoul-based aid group Good Friends. United States A sophisticated Bayesian analysis of public health data from April to the end of June from New York City and Milwaukee indicates that the pandemic's symptomatic case-fatality ratio has been far lower than the previous three pandemics of 1968, 1957, and 1918, making it to date the mildest pandemic on record. Afghanistan The 17th H1N1 fatality is reported. Gaza The eighth fatality is reported, that of a child with underlying kidney failure, within a week of the first H1N1 case in the Gaza Strip. United States CDC FluView Week 49: Widespread influenza activity in 11 states, regional activity in twenty. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the eleventh consecutive week... The proportion of outpatient visits for influenza-like illness (ILI) was 2.6% which is above the national baseline of 2.3%. Five of the 10 regions reported ILI at or above region-specific baseline levels." Georgia First fatality confirmed, that of a 27-year-old man. [ citation needed ] Qatar Mass vaccinations begin. United States Roughly 100 million H1N1 vaccines become widely available to the general public in pharmacies in several American states as the supply increases and restrictions to high-risk groups are lifted. Thailand First confirmed case of H1N1 in a pig, in a case of reverse zoonosis in Saraburi Province. The pig recovered. United States CDC FluView Week 50: The CDC reports that levels of influenza are declining steadily, with only seven states reporting widespread influenza activity and 18 reporting regional activity; furthermore, the proportion of deaths attributed to pneumonia and influenza (P&I) is below the epidemic threshold. The CDC also notes that almost all isolates of H1N1 remain sensitive to oseltamivir . "The proportion of outpatient visits for influenza-like illness (ILI) was 2.3% which is at the national baseline of 2.3%." US First case of canine zoonosis confirmed. The 13-year-old dog from New York state was believed to have contracted the virus from his owner. US H1N1 is discovered at two North Carolina pig farms, making it the 10th state to identify the virus in animals. The swine caught the disease from infected workers and recovered after becoming moderately ill. Argentina An Argentine study published in the New England Journal of Medicine shows that "Pediatric 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza than in previous years," and that the elevated risk for pregnant women extends for as long as two weeks after they give birth. US CDC FluView Week 51: Influenza activity decreases slightly, although the proportion of deaths attributed to P&I remained above the epidemic threshold. "Four states reported geographically widespread influenza activity, 13 states reported regional influenza activity, the District of Columbia, Puerto Rico, and 19 states reported local influenza activity, Guam and 13 states reported sporadic influenza activity, and one state reported no influenza activity, the U.S. Virgin Islands did not report." WHO At least 12,220 deaths globally are formally confirmed. (By contrast, the WHO estimates that the seasonal flu kills from 250,000 to 300,000 people around the world each year.) Overall, the activity of the H1N1 pandemic has peaked. Nepal First death confirmed, that of a woman who suffered major organ failure. WHO In Geneva Dr. Margaret Chan , Director-General of the WHO, remarks in the context of the H5N1 bird flu virus that "The fact that the long overdue influenza pandemic is so moderate in its impact is probably the best health news of the decade" but that "No, the world is not ready for a pandemic to be caused by H5N1." Given that H1N1 could still mutate, however, the WHO shall continue to monitor the pandemic for six months to a year. She also said that it would take at least two years before a true death total is established. (Approximately 11,500 people are believed to have died in more than 200 countries.) A study published in the New England Journal of Medicine finds that "household contacts less than 18 years of age were twice as susceptible to an acute respiratory illness as were those 19 to 50 years of age, whereas contacts older than 50 years were less susceptible". A joint US-UK study shows that children are twice as likely as adults to catch H1N1. Mexico In La Gloria, Veracruz 60% of the town's population is sickened by a respiratory illness of unknown provenance. The government of Mexico believes it to be caused by H3N2 influenza, though at least one patient in La Gloria tested positive for A/H1N1. Two babies died in the outbreak but both were buried without testing. United States In the ninth week of its routine influenza surveillance, the CDC reports on FluView that thirty-five states have reported widespread influenza activity, and 14 states have reported regional activity, but that although the rate of activity was high, that the proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold. United States The CDC reports on the 10th week of FluView that thirty states reported widespread influenza activity and 18 states reported regional activity. Mexico Earliest known onset of a case that is later to be confirmed as Swine-Origin Influenza A (H1N1) Virus Infection. United States CDC FluView, Week 11: Widespread influenza activity in twenty-four states; regional activity in 19. Influenza activity continues to decrease. United States Earliest known onset of a USA case later confirmed as swine flu, that of a nine-year-old girl residing in Imperial County, California . Thirteen states reported widespread influenza activity and 19 reported regional activity on the CDC's FluView, Week 12. United States A sample is collected from a nine-year-old female patient which is later confirmed to contain the novel virus strain (genetically sequenced as A/California/05/2009(H1N1)). United States Onset of illness for a ten-year-old boy residing in San Diego County, California ; his case is eventually the first to be confirmed as swine flu in the US. United States In the ninth week of its routine influenza surveillance, the CDC reports on FluView that thirty-five states have reported widespread influenza activity, and 14 states have reported regional activity, but that although the rate of activity was high, that the proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold. United States The CDC reports on the 10th week of FluView that thirty states reported widespread influenza activity and 18 states reported regional activity. Mexico Earliest known onset of a case that is later to be confirmed as Swine-Origin Influenza A (H1N1) Virus Infection. United States CDC FluView, Week 11: Widespread influenza activity in twenty-four states; regional activity in 19. Influenza activity continues to decrease. United States Earliest known onset of a USA case later confirmed as swine flu, that of a nine-year-old girl residing in Imperial County, California . Thirteen states reported widespread influenza activity and 19 reported regional activity on the CDC's FluView, Week 12. United States A sample is collected from a nine-year-old female patient which is later confirmed to contain the novel virus strain (genetically sequenced as A/California/05/2009(H1N1)). United States Onset of illness for a ten-year-old boy residing in San Diego County, California ; his case is eventually the first to be confirmed as swine flu in the US. United States A nasopharyngeal swab is collected from a ten-year-old male patient in San Diego County, later confirmed as containing the novel virus and the first organism of that strain to be completely sequenced (A/California/04/2009(H1N1)). Mexico In La Gloria, Veracruz , a four-year-old boy falls ill at the end of the outbreak. Only his sample, which was eventually sent abroad, tested positive for A(H1N1). Veracruz officials state that there were no plans to exhume the bodies of two infants who died in the outbreak. United States CDC FluView, Week 13: Widespread influenza activity in four states, regional activity in 18. European Union The media monitoring website MedISys reports on a Mexican article about the epidemiological alert. Mexico Public health authorities begin investigating unusual cases of pneumonia . 400 people had reportedly sought treatment for pneumonia/ influenza-like illness (ILI) in La Gloria the preceding week. United States Biosurveillance firm Veratect reports the unusual respiratory illness in Mexico. Veratect publishes the alert "La Gloria: 'Strange' Respiratory Affects 60% of Local Population; Three Pediatric Deaths May be Associated with the Outbreak." United States CDC FluView, Week 14: Widespread influenza activity in one state; regional activity in 14. Mexico The General Directorate of Epidemiology (DGE) reports the outbreak of an ILI in a small community in Veracruz to the Pan American Health Organization ( PAHO ), which is the Regional Office of the World Health Organization ( WHO ). Furthermore, a 39-year-old woman dies of severe viral pneumonia in the city of San Luis Potosí ; this is later believed to be the earliest known fatality related to the outbreak. Mexico First death in Oaxaca due to what would later be identified as swine flu. United States The U.S. Centers for Disease Control (CDC) is advised of a ten-year-old boy with a respiratory illness in San Diego County, California. Test results revealed an Influenza A virus but were negative for standard human strains. The San Diego County Health Department is notified. United States The CDC receives its first sample from California (from the ten-year-old boy in San Diego County), and identifies the virus as a strain of swine influenza A(H1N1). Mexico Authorities notify the PAHO of the atypical pneumonia . United States Veratect publishes the alert "Atypical Pneumonia Cases Reported at Hospital" regarding the Oaxaca cases. Mexico A case of atypical pneumonia in Oaxaca prompts enhanced national surveillance. A field investigation is started. Mexico contacts Canada to request more specialized testing. United States The CDC receives a second sample from Southern California (taken from the nine-year-old girl in Imperial County), and again identifies the virus as a strain of swine influenza A(H1N1). The California Department of Public Health is notified. Mexico Mexico sends 14 mucus samples to the CDC and dispatches health teams hospitals to look for patients showing severe influenza- or pneumonia-like symptoms. United States CDC FluView, Week 15: "Nine states reported regional activity; 17 states reported local influenza activity; the District of Columbia and 22 states reported sporadic influenza activity; and two states reported no influenza activity. Seven human infections with swine influenza A (H1N1) virus have been confirmed." This is the first mention of A(H1N1) in FluView. United States Veratect advises the CDC of the Mexican events. The CDC is already investigating the California and Texas cases. United States The CDC alerts physicians to a similar novel strain of swine influenza A(H1N1) in two cases from Southern California in a Morbidity and Mortality Weekly Report Early Release on its website. Local investigations, including investigations in Texas, are already underway, and overall surveillance is enhanced. The Associated Press covers the alert, the first mention of the A(H1N1) outbreak in English-language news media. Canada Canada receives the samples from Mexico for testing. Mexico The Public Health Agency of Canada confirms Mexico cases of swine-origin influenza A (H1N1) virus (S-OIV) infection. Genetic sequence analysis reveals that the Mexican patients were infected with the same S-OIV strain detected in two California children. The PAHO is informed that a cluster in Mexico of severe respiratory illnesses has been laboratory-confirmed as S-OIV infection. The WHO issues its first Disease Outbreak Notice on the matter, confirming the infection of a number of people in Mexico and the United States by "Swine Influenza A/H1N1 viruses... not... previously detected in pigs or humans". Mexico The Minister of Health confirms the Mexican cases of human infection by swine influenza and states that it believes that some of these cases had resulted in death. Health authorities implement public health measures for all airport passengers and the vaccination of health care workers with seasonal influenza vaccine . United States The CDC tells a press conference that seven of the 14 Mexican samples contained the same virus strain as the known in California and Texas, and that indications suggested that containment in the USA was "not very likely". The novel strain had already been reported on the CDC's Morbidity and Mortality Weekly Report website. WHO Under the International Health Regulations (IHR), the Emergency Committee convenes for the first time since its establishment in 2007, resulting in the WHO Director-General declaring a formal "public health emergency of international concern," ( PHEIC ), the first ever. The PAHO Vaccination Week In The Americas starts. The 2009 Week was planned to emphasize the vaccination of entire families, and health worker immunization . United States First closure of an entire school district, the Schertz-Cibolo-Universal City Independent School District outside San Antonio, Texas . United States United States declares a Public Health Emergency. WHO The Emergency Committee meets for the second time. The WHO Director-General issues a statement that containment of the outbreak is not feasible, and elevates the pandemic alert from Phase 3 to Phase 4. European Union (EU) Health Commissioner advises Europeans not to travel to the United States or Mexico unless the need is urgent. This follows the first confirmed case in Spain. Canada First six cases confirmed, four in Nova Scotia and two in British Columbia. Mexico First seven confirmed deaths Spain First confirmed case of swine flu, in Almansa , and thus the first case in Europe; A(H1N1) has spread from the WHO Region of the Americas to the WHO European Region. ( ) United Kingdom First two confirmed cases, in Scotland. WHO Confirmed cases are now extant in four of six WHO regions (see map). As of 19:15 GMT seven countries have officially reported cases of swine influenza A(H1N1) infection. Canada Confirmed: two cases and another four in Alberta and Ontario , respectively. Israel First confirmed case in Israel and thus the WHO Eastern Mediterranean Region (color-coded yellow), the third region to be affected. New Zealand First three confirmed cases in New Zealand and thus the WHO Western Pacific Region (color-coded red), the fourth region to be affected. Spain The second confirmed case in Spain, in Valencia . WHO The Emergency Committee meets for the third time, and the WHO raises its pandemic alert level from Phase 4 to Phase 5, its second highest. As of 1800 GMT, nine countries have officially reported 148 cases of swine influenza A(H1N1) infection. ASEAN ASEAN officials are looking at coordinating measures to address the potential pandemic. EU Foreign Relations Commissioner Benita Ferrero-Waldner announces that the halt of all travel to Mexico and disinfecting all airports due to the global flu outbreak is being considered. Austria First confirmed case. Germany First three confirmed cases, two in Bavaria and one in Hamburg . Spain Eight more cases raises the total in Spain to 10, including the first human-to-human intergenerational transmission (in which the patient had not recently been to Mexico but was infected by another patient who had just visited Mexico, namely his girlfriend). This is the first intergenerational transmission to be documented in Europe. United States First death outside Mexico, a 23-month-old Mexican child hospitalized in Texas. Ninety-one confirmed cases in the US to date. South Africa First two cases reported within South Africa, by two women that travelled in Mexico weeks earlier. The cases were confirmed on 18 June 2009. Canada Confirmed: One more case in Toronto , and eight more cases in Nova Scotia , and Alberta bringing total to 28. Ireland First confirmed case. Netherlands First confirmed case, a three-year-old child. The child returned from Mexico to the Netherlands on April 27, 2009. The parents test negative for A(H1N1). Switzerland First confirmed case. United States Four cases are confirmed in an outbreak at the University of Delaware ; another 12 cases are deemed "probable". One of the confirmed cases is a baseball player, which results in the university cancelling sporting events, a concert by rapper Young Jeezy , and other school activities. United Kingdom Three further confirmed cases of swine flu, giving a total of eight confirmed cases. United States A nasopharyngeal swab is collected from a ten-year-old male patient in San Diego County, later confirmed as containing the novel virus and the first organism of that strain to be completely sequenced (A/California/04/2009(H1N1)). Mexico In La Gloria, Veracruz , a four-year-old boy falls ill at the end of the outbreak. Only his sample, which was eventually sent abroad, tested positive for A(H1N1). Veracruz officials state that there were no plans to exhume the bodies of two infants who died in the outbreak. United States CDC FluView, Week 13: Widespread influenza activity in four states, regional activity in 18. European Union The media monitoring website MedISys reports on a Mexican article about the epidemiological alert. Mexico Public health authorities begin investigating unusual cases of pneumonia . 400 people had reportedly sought treatment for pneumonia/ influenza-like illness (ILI) in La Gloria the preceding week. United States Biosurveillance firm Veratect reports the unusual respiratory illness in Mexico. Veratect publishes the alert "La Gloria: 'Strange' Respiratory Affects 60% of Local Population; Three Pediatric Deaths May be Associated with the Outbreak." United States CDC FluView, Week 14: Widespread influenza activity in one state; regional activity in 14. Mexico The General Directorate of Epidemiology (DGE) reports the outbreak of an ILI in a small community in Veracruz to the Pan American Health Organization ( PAHO ), which is the Regional Office of the World Health Organization ( WHO ). Furthermore, a 39-year-old woman dies of severe viral pneumonia in the city of San Luis Potosí ; this is later believed to be the earliest known fatality related to the outbreak. Mexico First death in Oaxaca due to what would later be identified as swine flu. United States The U.S. Centers for Disease Control (CDC) is advised of a ten-year-old boy with a respiratory illness in San Diego County, California. Test results revealed an Influenza A virus but were negative for standard human strains. The San Diego County Health Department is notified. United States The CDC receives its first sample from California (from the ten-year-old boy in San Diego County), and identifies the virus as a strain of swine influenza A(H1N1). Mexico Authorities notify the PAHO of the atypical pneumonia . United States Veratect publishes the alert "Atypical Pneumonia Cases Reported at Hospital" regarding the Oaxaca cases. Mexico A case of atypical pneumonia in Oaxaca prompts enhanced national surveillance. A field investigation is started. Mexico contacts Canada to request more specialized testing. United States The CDC receives a second sample from Southern California (taken from the nine-year-old girl in Imperial County), and again identifies the virus as a strain of swine influenza A(H1N1). The California Department of Public Health is notified. Mexico Mexico sends 14 mucus samples to the CDC and dispatches health teams hospitals to look for patients showing severe influenza- or pneumonia-like symptoms. United States CDC FluView, Week 15: "Nine states reported regional activity; 17 states reported local influenza activity; the District of Columbia and 22 states reported sporadic influenza activity; and two states reported no influenza activity. Seven human infections with swine influenza A (H1N1) virus have been confirmed." This is the first mention of A(H1N1) in FluView. United States Veratect advises the CDC of the Mexican events. The CDC is already investigating the California and Texas cases. United States The CDC alerts physicians to a similar novel strain of swine influenza A(H1N1) in two cases from Southern California in a Morbidity and Mortality Weekly Report Early Release on its website. Local investigations, including investigations in Texas, are already underway, and overall surveillance is enhanced. The Associated Press covers the alert, the first mention of the A(H1N1) outbreak in English-language news media. Canada Canada receives the samples from Mexico for testing. Mexico The Public Health Agency of Canada confirms Mexico cases of swine-origin influenza A (H1N1) virus (S-OIV) infection. Genetic sequence analysis reveals that the Mexican patients were infected with the same S-OIV strain detected in two California children. The PAHO is informed that a cluster in Mexico of severe respiratory illnesses has been laboratory-confirmed as S-OIV infection. The WHO issues its first Disease Outbreak Notice on the matter, confirming the infection of a number of people in Mexico and the United States by "Swine Influenza A/H1N1 viruses... not... previously detected in pigs or humans". Mexico The Minister of Health confirms the Mexican cases of human infection by swine influenza and states that it believes that some of these cases had resulted in death. Health authorities implement public health measures for all airport passengers and the vaccination of health care workers with seasonal influenza vaccine . United States The CDC tells a press conference that seven of the 14 Mexican samples contained the same virus strain as the known in California and Texas, and that indications suggested that containment in the USA was "not very likely". The novel strain had already been reported on the CDC's Morbidity and Mortality Weekly Report website. WHO Under the International Health Regulations (IHR), the Emergency Committee convenes for the first time since its establishment in 2007, resulting in the WHO Director-General declaring a formal "public health emergency of international concern," ( PHEIC ), the first ever. The PAHO Vaccination Week In The Americas starts. The 2009 Week was planned to emphasize the vaccination of entire families, and health worker immunization . United States First closure of an entire school district, the Schertz-Cibolo-Universal City Independent School District outside San Antonio, Texas . United States United States declares a Public Health Emergency. WHO The Emergency Committee meets for the second time. The WHO Director-General issues a statement that containment of the outbreak is not feasible, and elevates the pandemic alert from Phase 3 to Phase 4. European Union (EU) Health Commissioner advises Europeans not to travel to the United States or Mexico unless the need is urgent. This follows the first confirmed case in Spain. Canada First six cases confirmed, four in Nova Scotia and two in British Columbia. Mexico First seven confirmed deaths Spain First confirmed case of swine flu, in Almansa , and thus the first case in Europe; A(H1N1) has spread from the WHO Region of the Americas to the WHO European Region. ( ) United Kingdom First two confirmed cases, in Scotland. WHO Confirmed cases are now extant in four of six WHO regions (see map). As of 19:15 GMT seven countries have officially reported cases of swine influenza A(H1N1) infection. Canada Confirmed: two cases and another four in Alberta and Ontario , respectively. Israel First confirmed case in Israel and thus the WHO Eastern Mediterranean Region (color-coded yellow), the third region to be affected. New Zealand First three confirmed cases in New Zealand and thus the WHO Western Pacific Region (color-coded red), the fourth region to be affected. Spain The second confirmed case in Spain, in Valencia . WHO The Emergency Committee meets for the third time, and the WHO raises its pandemic alert level from Phase 4 to Phase 5, its second highest. As of 1800 GMT, nine countries have officially reported 148 cases of swine influenza A(H1N1) infection. ASEAN ASEAN officials are looking at coordinating measures to address the potential pandemic. EU Foreign Relations Commissioner Benita Ferrero-Waldner announces that the halt of all travel to Mexico and disinfecting all airports due to the global flu outbreak is being considered. Austria First confirmed case. Germany First three confirmed cases, two in Bavaria and one in Hamburg . Spain Eight more cases raises the total in Spain to 10, including the first human-to-human intergenerational transmission (in which the patient had not recently been to Mexico but was infected by another patient who had just visited Mexico, namely his girlfriend). This is the first intergenerational transmission to be documented in Europe. United States First death outside Mexico, a 23-month-old Mexican child hospitalized in Texas. Ninety-one confirmed cases in the US to date. South Africa First two cases reported within South Africa, by two women that travelled in Mexico weeks earlier. The cases were confirmed on 18 June 2009.Canada Confirmed: One more case in Toronto , and eight more cases in Nova Scotia , and Alberta bringing total to 28. Ireland First confirmed case. Netherlands First confirmed case, a three-year-old child. The child returned from Mexico to the Netherlands on April 27, 2009. The parents test negative for A(H1N1). Switzerland First confirmed case. United States Four cases are confirmed in an outbreak at the University of Delaware ; another 12 cases are deemed "probable". One of the confirmed cases is a baseball player, which results in the university cancelling sporting events, a concert by rapper Young Jeezy , and other school activities. United Kingdom Three further confirmed cases of swine flu, giving a total of eight confirmed cases. WHO As of 0600 GMT, 11 countries have officially reported 331 cases of influenza A(H1N1) infection. Canada 51 confirmed cases. Hong Kong Denmark First confirmed case (in Hvidovre). France First two confirmed cases. Mexico begins an unprecedented five-day shutdown to fight the spread of the flu. United Kingdom First and second case of human to human (or intergenerational) transmission within the UK confirmed. United States 155 confirmed cases, including two at George Washington University's Thurston Hall. WHO As of 0600 GMT 15 countries have officially reported 615 cases of influenza A(H1N1) infection. Canada The Canadian Food Inspection Agency confirms the first human-to-animal transmission of the virus after an Albertan returns from Mexico and infects a pig farm, the first known case of (reverse) zoonosis . China suspends flights from Mexico. South Korea First confirmed case. United States There are more than 430 school closures in 18 states. CDC FluView Week 17: Widespread activity in seven states, regional activity in 12. WHO As of 0600 GMT, 17 countries have officially reported 787 cases of (A)H1N1. Arab League Health Ministers meet in Riyadh, to discuss human and technical support to be deployed in any Arab affected place. Canada 101 confirmed cases after seven cases in British Columbia , three in Alberta , two in Nova Scotia and Ontario , and one in Quebec were confirmed. Colombia First confirmed case in South America . WHO As of 06:00 GMT, 20 countries have officially reported 985 cases of influenza A (H1N1) infection. Canada A girl from Edmonton , Alberta was diagnosed with a severe case of the H1N1 virus. WHO As of 06:00 GMT, 21 countries have officially reported 1,124 cases of influenza A (H1N1) infection. United States WHO As of 06:00 GMT, 22 countries have officially reported 1,516 cases of influenza A (H1N1) infection. ASEAN A special regional summit to fight possible swine flu pandemic was held in Bangkok and was attended by senior ASEAN health officials along with those from China, Japan and South Korea. Guatemala First confirmed case, and the first in Central America. Poland First confirmed case. Sweden First confirmed case. WHO As of 18:00 GMT, 24 countries have officially reported 2,371 cases of influenza A (H1N1) infection. Argentina First confirmed case. Brazil First four confirmed cases. Canada Reports suggest that an elderly woman who had swine flu has died in northern Alberta, marking the first death in Canada related to swine flu. Furthermore, an unusual case of zoonosis occurred when a swine flu inspector in improper gear caught the virus from an infected pig. Netherlands Second case confirmed, a 53-year-old woman who had recently travelled to Mexico. USA The New England Journal of Medicine establishes its H1N1 Influenza Center on its website. WHO As of 16:00 GMT, 25 countries have officially reported 2,500 cases of influenza A (H1N1) infection. Japan First three confirmed cases. Panama First confirmed case. WHO As of 06:00 GMT, 29 countries have officially reported 3,440 cases of influenza A(H1N1) infection. Australia First confirmed case. Brazil Two cases confirmed, one of which is thought to be the first case of human-to-human infection in Brazil. Costa Rica First confirmed death, and also the first death outside of North America. Three other confirmed cases, all children, were contaminated by the patient who died. Japan 4th confirmed case, a schoolmate of the first three cases. Norway First two confirmed cases. United States Third confirmed death, a Washington man with underlying heart disease. Also, the USA passes Mexico in the number of confirmed cases of infection, 1693 to 1364, thus becoming the nation-state with the most laboratory-confirmed cases of infection; Canada is third with 242 cases. CDC FluView Week 18: Widespread influenza activity in eight states, regional activity in 14. WHO As of 07:30 GMT, 29 countries have officially reported 4,379 cases of influenza A(H1N1) infection. China First confirmed case. WHO As of 06:00 GMT, 30 countries have officially reported 4,694 cases of influenza A(H1N1) infection. WHO As of 06:00 GMT, 30 countries have officially reported 5,251 cases of influenza A(H1N1) infection. Canada The first case in Yukon Territory is confirmed. Spain 100 cases confirmed. WHO As of 06:00 GMT, 13 May 2009, 33 countries have officially reported 5,728 cases of influenza A(H1N1) infection. Belgium First confirmed case. Panama 10 more cases confirmed today. Total: 39. WHO As of 06:00 GMT, 33 countries have officially reported 6,497 cases of influenza A(H1N1) infection. Belgium Second confirmed case. Colombia First domestic infections with three cases confirmed. Total: 10. WHO As of 06:00 GMT, 34 countries have officially reported 7,520 cases of influenza A(H1N1) infection. USA Fourth and fifth deaths confirmed, that of an Arizona woman suffering from a lung condition and a Texas man in Corpus Christi, respectively. Malaysia First confirmed case. Malaysia is the 37th country to be affected by the virus. Panama Four new cases confirmed today. Total: 43, 23 of whom are male and 20 of whom are female. 20 of the cases are under 15 years old. WHO As of 06:00 GMT 36 countries have officially reported 8,451 cases of influenza A(H1N1) infection. India First case confirmed, in Hyderabad. This marks the arrival of A(H1N1) in the fifth of the WHO's six regions, the South-East Asia Region. Japan First domestic infection confirmed, in Kobe , a male high school student with no history of travel abroad. The Kobe Festival , planned for May 16 and 17, is cancelled. Malaysia Second confirmed case. The first patient is now showing significant improvement from the treatment. Panama 11 new confirmed cases. 54 total. Turkey First confirmed case, that of an American tourist flying from the United States via Amsterdam, discovered at Istanbul's Atatürk International Airport. United States CDC FluView Week 19: Widespread influenza activity in five states, regional activity in 13. WHO As of 06:00 GMT 37 countries have officially reported 8,480 cases of influenza A(H1N1) infection. Panama With 54 confirmed cases, Panama occupies second place, along with Canada, for the number of cases per country. WHO As of 06:00 GMT, 40 countries have officially reported 8,829 cases of influenza A(H1N1) infection, including 74 deaths. ECDC The European Centre for Disease Control releases its early findings on H1N1's pandemic potential. Japan reports 96 confirmed cases; it now ranks fourth in the world in the number of infections. Thousands of schools in 21 cities in the Hyogo and Osaka prefectures are temporarily closed. USA The sixth death in the US, and the first in New York—that of an assistant principal. WHO As of 06:00 GMT, 40 countries have officially reported 9,830 cases of influenza A(H1N1) infection, including 79 deaths. United States Seventh confirmed death, that of a 44-year-old Missouri man. Japan 191 confirmed cases; Hyogo Prefecture has the most at 111. Norway One more case confirmed today. Total: three. Paraguay confirmed its first case and became the 43rd affected country. Taiwan confirmed its first case and becomes the 44th affected country. WHO As of 06:00 GMT, 40 countries have officially reported 10,243 cases of influenza A(H1N1) infection, including 80 deaths. United States A patient dies in Arizona, and a 22-year-old man dies in Utah, the nation's eighth and ninth H1N1 fatalities. Roughly half of the influenza viruses detected by the CDC's routine influenza surveillance systems are now that of novel A(H1N1). An unusual number of outbreaks in schools is reported. Japan 236 confirmed cases, including the first case in Shiga Prefecture , and the cities of Hachiōji and Kawasaki in the Greater Tokyo Area . Two female high school students from Tokyo who had recently attended a Model United Nations conference in New York are presumed to have become infected abroad. Norway 1 more case confirmed today. Total: 4. WHO As of 06:00 GMT, 41 countries have officially reported 11,034 cases of influenza A(H1N1) infection, including 85 deaths. Japan 279 confirmed cases; more than 4,800 schools are closed in the Kobe region. WHO As of 06:00 GMT, 42 countries have officially reported 11,168 cases of influenza A(H1N1) infection, including 86 deaths. Japan 317 confirmed, including first confirmed in Saitama Prefecture . Third confirmed in Tokyo, a 25-year-old man who visited Osaka from May 14-20th. Philippines First case confirmed. WHO As of 06:00 GMT, 43 countries have officially reported 12,022 cases of influenza A(H1N1) infection, including 86 deaths. Iceland First confirmed case. 4 more cases suspected. United States CDC FluView Week 20: Widespread influenza activity in four states; regional activity in 11. Australia Two more confirmed cases, which now brings the national toll to 16. Kuwait First confirmed cases, that of 18 U.S. soldiers. WHO As of 06:00 GMT, 46 countries have officially reported 12,515 cases of influenza A(H1N1) infection, including 91 deaths. Australia 22 Confirmed Cases. Ireland Second confirmed case. WHO As of 06:00 GMT, 46 countries have officially reported 12,954 cases of influenza A(H1N1) infection, including 92 deaths. Argentina 14 Confirmed Cases. Total: 19. Australia 61 confirmed cases. Puerto Rico First confirmed case. WHO As of 06:00 GMT, 48 countries have officially reported 13,398 cases of influenza A(H1N1) infection, including 95 deaths Argentina 37 cases confirmed. Dominican Republic First two confirmed cases. Greece confirmed two more cases. Romania First confirmed case. Singapore First confirmed case. A 22-year-old woman picked up the virus after visiting New York. United Kingdom Two new cases confirmed. Total: 186. Uruguay confirmed its first two cases. Australia 147 confirmed cases. Singapore Three more cases confirmed. Total confirmed cases now stands at four. United Kingdom Seventeen more confirmed cases. Total: 203. Bolivia First 2 cases confirmed. Venezuela First confirmed case. WHO As of 06:00 GMT, 53 countries have officially reported 15,510 cases of influenza A(H1N1) infection, including 99 deaths United Kingdom 14 confirmed cases. Total: 217. Norway One new confirmed case. Total: 5. Hungary First confirmed case Uruguay 4 new confirmed cases. Total: 6. Greece Another one case confirmed. Total: 4. Estonia First confirmed case. United States CDC FluView Week 21: Widespread influenza activity in five states, regional activity in 10. Dominican Republic Nine more cases confirmed, for a total of 11 cases nationwide. WHO As of 0600 GMT, 11 countries have officially reported 331 cases of influenza A(H1N1) infection. Canada 51 confirmed cases. Hong Kong Denmark First confirmed case (in Hvidovre). France First two confirmed cases. Mexico begins an unprecedented five-day shutdown to fight the spread of the flu. United Kingdom First and second case of human to human (or intergenerational) transmission within the UK confirmed. United States 155 confirmed cases, including two at George Washington University's Thurston Hall. WHO As of 0600 GMT 15 countries have officially reported 615 cases of influenza A(H1N1) infection. Canada The Canadian Food Inspection Agency confirms the first human-to-animal transmission of the virus after an Albertan returns from Mexico and infects a pig farm, the first known case of (reverse) zoonosis . China suspends flights from Mexico. South Korea First confirmed case. United States There are more than 430 school closures in 18 states. CDC FluView Week 17: Widespread activity in seven states, regional activity in 12. WHO As of 0600 GMT, 17 countries have officially reported 787 cases of (A)H1N1. Arab League Health Ministers meet in Riyadh, to discuss human and technical support to be deployed in any Arab affected place. Canada 101 confirmed cases after seven cases in British Columbia , three in Alberta , two in Nova Scotia and Ontario , and one in Quebec were confirmed. Colombia First confirmed case in South America . WHO As of 06:00 GMT, 20 countries have officially reported 985 cases of influenza A (H1N1) infection. Canada A girl from Edmonton , Alberta was diagnosed with a severe case of the H1N1 virus. WHO As of 06:00 GMT, 21 countries have officially reported 1,124 cases of influenza A (H1N1) infection. United StatesWHO As of 06:00 GMT, 22 countries have officially reported 1,516 cases of influenza A (H1N1) infection. ASEAN A special regional summit to fight possible swine flu pandemic was held in Bangkok and was attended by senior ASEAN health officials along with those from China, Japan and South Korea. Guatemala First confirmed case, and the first in Central America. Poland First confirmed case. Sweden First confirmed case. WHO As of 18:00 GMT, 24 countries have officially reported 2,371 cases of influenza A (H1N1) infection. Argentina First confirmed case. Brazil First four confirmed cases. Canada Reports suggest that an elderly woman who had swine flu has died in northern Alberta, marking the first death in Canada related to swine flu. Furthermore, an unusual case of zoonosis occurred when a swine flu inspector in improper gear caught the virus from an infected pig. Netherlands Second case confirmed, a 53-year-old woman who had recently travelled to Mexico. USA The New England Journal of Medicine establishes its H1N1 Influenza Center on its website. WHO As of 16:00 GMT, 25 countries have officially reported 2,500 cases of influenza A (H1N1) infection. Japan First three confirmed cases. Panama First confirmed case. WHO As of 06:00 GMT, 29 countries have officially reported 3,440 cases of influenza A(H1N1) infection. Australia First confirmed case. Brazil Two cases confirmed, one of which is thought to be the first case of human-to-human infection in Brazil. Costa Rica First confirmed death, and also the first death outside of North America. Three other confirmed cases, all children, were contaminated by the patient who died. Japan 4th confirmed case, a schoolmate of the first three cases. Norway First two confirmed cases. United States Third confirmed death, a Washington man with underlying heart disease. Also, the USA passes Mexico in the number of confirmed cases of infection, 1693 to 1364, thus becoming the nation-state with the most laboratory-confirmed cases of infection; Canada is third with 242 cases. CDC FluView Week 18: Widespread influenza activity in eight states, regional activity in 14. WHO As of 07:30 GMT, 29 countries have officially reported 4,379 cases of influenza A(H1N1) infection. China First confirmed case. WHO As of 06:00 GMT, 30 countries have officially reported 4,694 cases of influenza A(H1N1) infection. WHO As of 06:00 GMT, 30 countries have officially reported 5,251 cases of influenza A(H1N1) infection. Canada The first case in Yukon Territory is confirmed. Spain 100 cases confirmed. WHO As of 06:00 GMT, 13 May 2009, 33 countries have officially reported 5,728 cases of influenza A(H1N1) infection. Belgium First confirmed case. Panama 10 more cases confirmed today. Total: 39. WHO As of 06:00 GMT, 33 countries have officially reported 6,497 cases of influenza A(H1N1) infection. Belgium Second confirmed case. Colombia First domestic infections with three cases confirmed. Total: 10. WHO As of 06:00 GMT, 34 countries have officially reported 7,520 cases of influenza A(H1N1) infection. USA Fourth and fifth deaths confirmed, that of an Arizona woman suffering from a lung condition and a Texas man in Corpus Christi, respectively. Malaysia First confirmed case. Malaysia is the 37th country to be affected by the virus. Panama Four new cases confirmed today. Total: 43, 23 of whom are male and 20 of whom are female. 20 of the cases are under 15 years old. WHO As of 06:00 GMT 36 countries have officially reported 8,451 cases of influenza A(H1N1) infection. India First case confirmed, in Hyderabad. This marks the arrival of A(H1N1) in the fifth of the WHO's six regions, the South-East Asia Region. Japan First domestic infection confirmed, in Kobe , a male high school student with no history of travel abroad. The Kobe Festival , planned for May 16 and 17, is cancelled. Malaysia Second confirmed case. The first patient is now showing significant improvement from the treatment. Panama 11 new confirmed cases. 54 total. Turkey First confirmed case, that of an American tourist flying from the United States via Amsterdam, discovered at Istanbul's Atatürk International Airport. United States CDC FluView Week 19: Widespread influenza activity in five states, regional activity in 13. WHO As of 06:00 GMT 37 countries have officially reported 8,480 cases of influenza A(H1N1) infection. Panama With 54 confirmed cases, Panama occupies second place, along with Canada, for the number of cases per country.WHO As of 06:00 GMT, 40 countries have officially reported 8,829 cases of influenza A(H1N1) infection, including 74 deaths. ECDC The European Centre for Disease Control releases its early findings on H1N1's pandemic potential. Japan reports 96 confirmed cases; it now ranks fourth in the world in the number of infections. Thousands of schools in 21 cities in the Hyogo and Osaka prefectures are temporarily closed. USA The sixth death in the US, and the first in New York—that of an assistant principal. WHO As of 06:00 GMT, 40 countries have officially reported 9,830 cases of influenza A(H1N1) infection, including 79 deaths. United States Seventh confirmed death, that of a 44-year-old Missouri man. Japan 191 confirmed cases; Hyogo Prefecture has the most at 111. Norway One more case confirmed today. Total: three. Paraguay confirmed its first case and became the 43rd affected country. Taiwan confirmed its first case and becomes the 44th affected country. WHO As of 06:00 GMT, 40 countries have officially reported 10,243 cases of influenza A(H1N1) infection, including 80 deaths. United States A patient dies in Arizona, and a 22-year-old man dies in Utah, the nation's eighth and ninth H1N1 fatalities. Roughly half of the influenza viruses detected by the CDC's routine influenza surveillance systems are now that of novel A(H1N1). An unusual number of outbreaks in schools is reported. Japan 236 confirmed cases, including the first case in Shiga Prefecture , and the cities of Hachiōji and Kawasaki in the Greater Tokyo Area . Two female high school students from Tokyo who had recently attended a Model United Nations conference in New York are presumed to have become infected abroad. Norway 1 more case confirmed today. Total: 4. WHO As of 06:00 GMT, 41 countries have officially reported 11,034 cases of influenza A(H1N1) infection, including 85 deaths. Japan 279 confirmed cases; more than 4,800 schools are closed in the Kobe region. WHO As of 06:00 GMT, 42 countries have officially reported 11,168 cases of influenza A(H1N1) infection, including 86 deaths. Japan 317 confirmed, including first confirmed in Saitama Prefecture . Third confirmed in Tokyo, a 25-year-old man who visited Osaka from May 14-20th. Philippines First case confirmed. WHO As of 06:00 GMT, 43 countries have officially reported 12,022 cases of influenza A(H1N1) infection, including 86 deaths. Iceland First confirmed case. 4 more cases suspected. United States CDC FluView Week 20: Widespread influenza activity in four states; regional activity in 11. Australia Two more confirmed cases, which now brings the national toll to 16. Kuwait First confirmed cases, that of 18 U.S. soldiers. WHO As of 06:00 GMT, 46 countries have officially reported 12,515 cases of influenza A(H1N1) infection, including 91 deaths. Australia 22 Confirmed Cases. Ireland Second confirmed case. WHO As of 06:00 GMT, 46 countries have officially reported 12,954 cases of influenza A(H1N1) infection, including 92 deaths. Argentina 14 Confirmed Cases. Total: 19. Australia 61 confirmed cases. Puerto Rico First confirmed case. WHO As of 06:00 GMT, 48 countries have officially reported 13,398 cases of influenza A(H1N1) infection, including 95 deaths Argentina 37 cases confirmed. Dominican Republic First two confirmed cases. Greece confirmed two more cases. Romania First confirmed case. Singapore First confirmed case. A 22-year-old woman picked up the virus after visiting New York. United Kingdom Two new cases confirmed. Total: 186. Uruguay confirmed its first two cases. Australia 147 confirmed cases. Singapore Three more cases confirmed. Total confirmed cases now stands at four. United Kingdom Seventeen more confirmed cases. Total: 203. Bolivia First 2 cases confirmed. Venezuela First confirmed case. WHO As of 06:00 GMT, 53 countries have officially reported 15,510 cases of influenza A(H1N1) infection, including 99 deaths United Kingdom 14 confirmed cases. Total: 217. Norway One new confirmed case. Total: 5. Hungary First confirmed case Uruguay 4 new confirmed cases. Total: 6. Greece Another one case confirmed. Total: 4. Estonia First confirmed case. United States CDC FluView Week 21: Widespread influenza activity in five states, regional activity in 10. Dominican Republic Nine more cases confirmed, for a total of 11 cases nationwide. WHO As of 06:00 GMT, 62 countries have officially reported 17,410 cases of influenza A(H1N1) infection, including 115 deaths. Bulgaria First confirmed case. Bermuda First case confirmed. Egypt First case confirmed. Luxembourg First case confirmed. Nicaragua First case confirmed. WHO As of 06:00 GMT, 3 June 2009, 66 countries have officially reported 19,273 cases of influenza A(H1N1) infection, including 117 deaths. Saudi Arabia First confirmed case. Barbados First confirmed case. Malaysia Three more cases confirmed. One of the patients is a 23-year-old student returned from the United States. Another two patients are German tourists who arrived in Singapore after having gone to Malaysia for holiday. Total: 5. Trinidad and Tobago First confirmed case. WHO As of 06:00 GMT, 69 countries have officially reported 21,940 cases of influenza A(H1N1) infection, including 125 deaths. Australia 1006 cases confirmed. Cayman Islands First case confirmed. Dominican Republic First fatality, a 17-year-old pregnant girl. Total number of confirmed cases rises to 44. Ukraine First confirmed case. Malaysia One more case confirmed. Total: 7. United States CDC FluView Week 22: Widespread influenza activity in eight states, regional activity in nine. "Approximately 89% of all influenza viruses being reported to CDC were novel influenza A (H1N1) viruses." Chile Second death confirmed. Martinique First case confirmed. New Zealand Authorities have confirmed that a man traveling from North America has Influenza A(H1N1). Total: 14. WHO As of 06:00 GMT, 73 countries have officially reported 25,288 cases of influenza A(H1N1) infection, including 139 deaths. Dominica First confirmed case. New Zealand Three more confirmed cases, two of which were from international flights. Total: 17. WHO As of 06:00 GMT, 74 countries have officially reported 27,737 cases of influenza A(H1N1) infection, including 141 deaths. Colombia First death confirmed. French Polynesia First confirmed case in the islands. Guatemala First death confirmed. The WHO raises its Pandemic Alert Level to Phase 6, citing significant transmission of the virus. Australia 1263 cases nationally, with more than 1000 cases in the State of Victoria alone. British Virgin Islands First case confirmed in the islands. Cuba Sixth case on the island, and that of the first citizen. Palestinian Territories First case confirmed in the West Bank. WHO As of 07:00 GMT, 12 June 2009, 74 countries have officially reported 29,669 cases of Influenza A (H1N1) infections, including 145 deaths. Morocco First case confirmed. Isle of Man First case confirmed. Bolivia First two domestic infections. Total: 7. Malaysia One more confirmed case. Total: 12. United States Widespread influenza activity in eleven states, regional activity in six. "Over 98% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." Malaysia Five more cases of H1N1 confirmed. Total: 17. United Kingdom First death confirmed. Sri Lanka First confirmed case. Monaco First confirmed case. Malaysia Four more cases of H1N1 confirmed. One domestic infection confirmed. Total: 23. Antigua and Barbuda First confirmed case. Bangladesh First confirmed case. Ethiopia First two cases confirmed. Slovenia First confirmed case. Philippines First death in Asia confirmed. H1N1 deaths now confirmed in 3 of 6 WHO regions. Iraq First seven cases confirmed. Japan 52 more cases confirmed. Total: 944. Serbia First confirmed case. United States CDC FluView Week 24: Widespread influenza activity in twelve states, regional activity in seven. "Over 99% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." United States CDC FluView Week 25: Widespread influenza activity in ten states, regional in 11 states. Bosnia and Herzegovina First case confirmed. Denmark First case of Oseltamivir (Tamiflu) resistance found. Confirmed by David Reddy, Roche's pandemic taskforce leader. Kenya First confirmed case. Mauritius First case confirmed. Nepal First three confirmed cases. South Africa South Africa National Health Department confirm community outbreak, with 7 new confirmed cases. The total of confirmed cases grew to 12640 within South Africa over the next few months. [ citation needed ]WHO As of 06:00 GMT, 62 countries have officially reported 17,410 cases of influenza A(H1N1) infection, including 115 deaths. Bulgaria First confirmed case. Bermuda First case confirmed. Egypt First case confirmed. Luxembourg First case confirmed. Nicaragua First case confirmed. WHO As of 06:00 GMT, 3 June 2009, 66 countries have officially reported 19,273 cases of influenza A(H1N1) infection, including 117 deaths. Saudi Arabia First confirmed case. Barbados First confirmed case. Malaysia Three more cases confirmed. One of the patients is a 23-year-old student returned from the United States. Another two patients are German tourists who arrived in Singapore after having gone to Malaysia for holiday. Total: 5. Trinidad and Tobago First confirmed case. WHO As of 06:00 GMT, 69 countries have officially reported 21,940 cases of influenza A(H1N1) infection, including 125 deaths. Australia 1006 cases confirmed. Cayman Islands First case confirmed. Dominican Republic First fatality, a 17-year-old pregnant girl. Total number of confirmed cases rises to 44. Ukraine First confirmed case.Malaysia One more case confirmed. Total: 7. United States CDC FluView Week 22: Widespread influenza activity in eight states, regional activity in nine. "Approximately 89% of all influenza viruses being reported to CDC were novel influenza A (H1N1) viruses." Chile Second death confirmed. Martinique First case confirmed. New Zealand Authorities have confirmed that a man traveling from North America has Influenza A(H1N1). Total: 14. WHO As of 06:00 GMT, 73 countries have officially reported 25,288 cases of influenza A(H1N1) infection, including 139 deaths. Dominica First confirmed case. New Zealand Three more confirmed cases, two of which were from international flights. Total: 17. WHO As of 06:00 GMT, 74 countries have officially reported 27,737 cases of influenza A(H1N1) infection, including 141 deaths. Colombia First death confirmed. French Polynesia First confirmed case in the islands. Guatemala First death confirmed. The WHO raises its Pandemic Alert Level to Phase 6, citing significant transmission of the virus. Australia 1263 cases nationally, with more than 1000 cases in the State of Victoria alone. British Virgin Islands First case confirmed in the islands. Cuba Sixth case on the island, and that of the first citizen. Palestinian Territories First case confirmed in the West Bank. WHO As of 07:00 GMT, 12 June 2009, 74 countries have officially reported 29,669 cases of Influenza A (H1N1) infections, including 145 deaths. Morocco First case confirmed. Isle of Man First case confirmed. Bolivia First two domestic infections. Total: 7. Malaysia One more confirmed case. Total: 12. United States Widespread influenza activity in eleven states, regional activity in six. "Over 98% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." Malaysia Five more cases of H1N1 confirmed. Total: 17. United Kingdom First death confirmed. Sri Lanka First confirmed case. Monaco First confirmed case. Malaysia Four more cases of H1N1 confirmed. One domestic infection confirmed. Total: 23. Antigua and Barbuda First confirmed case. Bangladesh First confirmed case. Ethiopia First two cases confirmed. Slovenia First confirmed case. Philippines First death in Asia confirmed. H1N1 deaths now confirmed in 3 of 6 WHO regions. Iraq First seven cases confirmed. Japan 52 more cases confirmed. Total: 944. Serbia First confirmed case. United States CDC FluView Week 24: Widespread influenza activity in twelve states, regional activity in seven. "Over 99% of all subtyped influenza A viruses being reported to CDC were pandemic influenza A (H1N1) viruses." United States CDC FluView Week 25: Widespread influenza activity in ten states, regional in 11 states. Bosnia and Herzegovina First case confirmed. Denmark First case of Oseltamivir (Tamiflu) resistance found. Confirmed by David Reddy, Roche's pandemic taskforce leader. Kenya First confirmed case. Mauritius First case confirmed. Nepal First three confirmed cases. South Africa South Africa National Health Department confirm community outbreak, with 7 new confirmed cases. The total of confirmed cases grew to 12640 within South Africa over the next few months. [ citation needed ]Guam First case confirmed. Australia First confirmed death in NSW . National total: 10. Japan Second case found with mutation resulting in Oseltamivir (Tamiflu) resistance. United States CDC FluView Week 26: Widespread influenza activity in nine states, regional influenza activity in 12. "Over 97% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Portugal First human-to-human transmission. Total: 38. Syria First case confirmed. Peru First two deaths confirmed. WHO 429 deaths worldwide are reported. Belize First five cases confirmed. Tanzania First case confirmed. United States CDC FluView Week 27: Widespread influenza activity in nine states, regional activity in 12. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Colombia 6th death case confirmed out of 165 infected Malaysia 39 more cases confirmed. Total: 710. United Kingdom Another 2 deaths confirmed. Total Deaths: 17. Brazil One more death confirmed. Total Deaths: 3. Ecuador Third death confirmed. Total deaths: 3. Brazil Fourth death confirmed. Malaysia 32 more cases confirmed. Total: 804 New Zealand Two more deaths confirmed. Total deaths 9. Total confirmed cases: 1,984. Singapore First flu-related death confirmed, that of a 49-year-old man with heart problems. Sudan First two confirmed cases of H1N1 detected, from flights which had arrived from the U.K. Hawaii First death, that of a sexagenarian with underlying health problems. United States CDC FluView Week 28: Widespread influenza activity in seven states, regional activity in 13. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Venezuela First death confirmed, that of an 11-year-old girl. Singapore First death with H1N1 involvement confirmed, that of a 49-year-old male who also suffered from diabetes, hypertension and high cholesterol, from a heart attack caused by severe pneumonia. Egypt First death confirmed. Georgia First case confirmed. Albania First case confirmed. Guam First death confirmed. Namibia First two H1N1 cases confirmed. Canada The fourth case of mutation in the world from Tamiflu has been found in a 60-year-old man from Quebec , Canada . Federated States of Micronesia First case confirmed, that of a 27-year-old male. Northern Mariana Islands First two cases of H1N1 confirmed. Hungary First death confirmed, that of a man with underlying heart and lung disease. Tonga First death confirmed. The WHO ceases the tracking of cumulative individual cases. Arab League Health Ministers hold a summit after the death of a pilgrim who had returned from the Hajj . New regulations were promulgated for the Hajj: anyone younger than 12 or older than 65 or who have "chronic health problems" shall not be allowed to undertake the pilgrimage to Mecca. Bhutan First case confirmed. Malaysia First flu-related death confirmed, that of an obese 30-year-old male. Canada Nova Scotia reports its first H1N1 death. Cayman Islands First death reported, that of a man with underlying medical conditions. Indonesia First H1N1 death confirmed, that of a 6-year-old girl suffering from severe pneumonia. United States It is reported that thousands of Americans are being recruited for H1N1 vaccine testing at several research centers across the country. CDC FluView Week 29: Widespread influenza activity in four states, regional activity in eight. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Norway An international 4H youth camp with 1,700 participants from fifteen nations is shut down after fifty Norwegian participants catch H1N1. WHO 816 deaths worldwide are reported. Germany Germany's federal infectious disease center, the Robert Koch Institute , states there were 3,810 confirmed cases of H1N1 in the country; nearly all of the cases are mild. Israel First death confirmed, that of a 35-year-old man from Eilat. Kosovo First case confirmed. Saint Kitts and Nevis First death reported, that of a 28-year-old woman. Saudi Arabia First death confirmed. Japan Third case of Oseltamivir (Tamiflu) resistance. Thailand In the first reported case of vertical transmission of A(H1N1), a baby is born infected. Swaziland First case confirmed. United Kingdom The NHS is not ready for a second wave of swine flu cases expected this autumn, a House of Lords committee has stated. It warned hospitals do not have enough intensive care beds to cope, and furthermore predicted that the recently established A(H1N1) flu helpline could be overwhelmed with calls. United States The U.S. military wants to establish regional teams of military personnel to assist civilian authorities in the event of a significant outbreak of the H1N1 virus this fall, according to Defense Department officials. Azerbaijan First two cases of A(H1N1) confirmed, those of people who had been on holiday in France and the U.K., respectively. Belgium First death confirmed, that of a 34-year-old woman. France First death confirmed, a 14-year-old girl in Brest . Gabon First case confirmed. Lebanon First death confirmed, that of a 30-year-old male. Moldova First case confirmed. Saudi Arabia Second H1N1 death confirmed, that a 28-year-old Indonesian woman. Taiwan First death confirmed, that of a 39-year-old man. WHO 1,154 deaths worldwide are reported. France The cruise ship Voyager of the Seas , which had reported dozens of cases of H1N1 flu amongst its 5,000 passengers and crew, docks in France. Guam First case confirmed. Australia First confirmed death in NSW . National total: 10. Japan Second case found with mutation resulting in Oseltamivir (Tamiflu) resistance. United States CDC FluView Week 26: Widespread influenza activity in nine states, regional influenza activity in 12. "Over 97% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Portugal First human-to-human transmission. Total: 38. Syria First case confirmed. Peru First two deaths confirmed. WHO 429 deaths worldwide are reported. Belize First five cases confirmed. Tanzania First case confirmed.United States CDC FluView Week 27: Widespread influenza activity in nine states, regional activity in 12. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Colombia 6th death case confirmed out of 165 infected Malaysia 39 more cases confirmed. Total: 710. United Kingdom Another 2 deaths confirmed. Total Deaths: 17.Brazil One more death confirmed. Total Deaths: 3. Ecuador Third death confirmed. Total deaths: 3. Brazil Fourth death confirmed. Malaysia 32 more cases confirmed. Total: 804 New Zealand Two more deaths confirmed. Total deaths 9. Total confirmed cases: 1,984.Singapore First flu-related death confirmed, that of a 49-year-old man with heart problems. Sudan First two confirmed cases of H1N1 detected, from flights which had arrived from the U.K. Hawaii First death, that of a sexagenarian with underlying health problems. United States CDC FluView Week 28: Widespread influenza activity in seven states, regional activity in 13. "Over 99% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Venezuela First death confirmed, that of an 11-year-old girl. Singapore First death with H1N1 involvement confirmed, that of a 49-year-old male who also suffered from diabetes, hypertension and high cholesterol, from a heart attack caused by severe pneumonia. Egypt First death confirmed. Georgia First case confirmed. Albania First case confirmed. Guam First death confirmed. Namibia First two H1N1 cases confirmed. Canada The fourth case of mutation in the world from Tamiflu has been found in a 60-year-old man from Quebec , Canada . Federated States of Micronesia First case confirmed, that of a 27-year-old male. Northern Mariana Islands First two cases of H1N1 confirmed. Hungary First death confirmed, that of a man with underlying heart and lung disease. Tonga First death confirmed. The WHO ceases the tracking of cumulative individual cases. Arab League Health Ministers hold a summit after the death of a pilgrim who had returned from the Hajj . New regulations were promulgated for the Hajj: anyone younger than 12 or older than 65 or who have "chronic health problems" shall not be allowed to undertake the pilgrimage to Mecca. Bhutan First case confirmed. Malaysia First flu-related death confirmed, that of an obese 30-year-old male. Canada Nova Scotia reports its first H1N1 death. Cayman Islands First death reported, that of a man with underlying medical conditions. Indonesia First H1N1 death confirmed, that of a 6-year-old girl suffering from severe pneumonia. United States It is reported that thousands of Americans are being recruited for H1N1 vaccine testing at several research centers across the country. CDC FluView Week 29: Widespread influenza activity in four states, regional activity in eight. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." Norway An international 4H youth camp with 1,700 participants from fifteen nations is shut down after fifty Norwegian participants catch H1N1. WHO 816 deaths worldwide are reported. Germany Germany's federal infectious disease center, the Robert Koch Institute , states there were 3,810 confirmed cases of H1N1 in the country; nearly all of the cases are mild. Israel First death confirmed, that of a 35-year-old man from Eilat. Kosovo First case confirmed. Saint Kitts and Nevis First death reported, that of a 28-year-old woman. Saudi Arabia First death confirmed. Japan Third case of Oseltamivir (Tamiflu) resistance. Thailand In the first reported case of vertical transmission of A(H1N1), a baby is born infected. Swaziland First case confirmed. United Kingdom The NHS is not ready for a second wave of swine flu cases expected this autumn, a House of Lords committee has stated. It warned hospitals do not have enough intensive care beds to cope, and furthermore predicted that the recently established A(H1N1) flu helpline could be overwhelmed with calls. United States The U.S. military wants to establish regional teams of military personnel to assist civilian authorities in the event of a significant outbreak of the H1N1 virus this fall, according to Defense Department officials. Azerbaijan First two cases of A(H1N1) confirmed, those of people who had been on holiday in France and the U.K., respectively. Belgium First death confirmed, that of a 34-year-old woman. France First death confirmed, a 14-year-old girl in Brest . Gabon First case confirmed. Lebanon First death confirmed, that of a 30-year-old male. Moldova First case confirmed. Saudi Arabia Second H1N1 death confirmed, that a 28-year-old Indonesian woman. Taiwan First death confirmed, that of a 39-year-old man. WHO 1,154 deaths worldwide are reported. France The cruise ship Voyager of the Seas , which had reported dozens of cases of H1N1 flu amongst its 5,000 passengers and crew, docks in France. Australia First case of reverse zoonosis confirmed in a piggery in Dunedoo . United States CDC FluView Week 30: Widespread influenza activity in four states, regional activity in 11. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." South Africa First confirmed death in South Africa. Total number of deaths at end of epidemic 93. [ citation needed ] India First death confirmed. Netherlands First death confirmed, that of a 17-year-old male. Solomon Islands First case confirmed. WHO 1,462 deaths worldwide are reported. United States CDC FluView Week 31: Widespread influenza activity in four states, regional activity in 10. Costa Rica President Óscar Arias is confirmed to have swine flu, the first head of state known to have been infected. WHO 1,799 deaths worldwide are reported. Madagascar First case confirmed. Democratic Republic of the Congo First H1N1 case confirmed. United States CDC FluView Week 32: Widespread influenza activity in two states, regional activity in eight. Malaysia Two more deaths confirmed. Total: 64 deaths. Malta First death confirmed. Malaysia Three more deaths confirmed. Total: 67 deaths. Belarus First H1N1 case confirmed. [ citation needed ] Kuwait First death confirmed. Malaysia One more death confirmed. Total: 68 deaths. The unusually high reported death rate, four times the global average, is investigated by the WHO. Netherlands Second death confirmed, that of a 58-year-old male. Chile H1N1 is found in turkeys on farms in Chile near the port city of Valparaiso in a unique zoonosis cluster. Germany 13,740 A(H1N1) cases confirmed. Oman First death confirmed. United Arab Emirates First death confirmed. United Kingdom First death confirmed in Northern Ireland, that of woman with underlying health conditions. New Caledonia First death confirmed. United States CDC FluView Week 33: Widespread influenza activity in two states, regional activity in 13. Activity appears to be increasing in the Southeast. WHO At least 2,185 deaths worldwide are reported. Greece First death confirmed. Germany 14,325 H1N1 cases confirmed. Kyrgyzstan First two cases confirmed, that of a husband and wife; the man had recently traveled to Dubai. Malaysia One more death confirmed. Total: 69 deaths. Malaysia One more death confirmed. Total: 70 deaths. Angola First case confirmed. Germany 14,940 H1N1 cases confirmed. Iran First death confirmed [ citation needed ] Malaysia One more death confirmed. Total: 71 deaths. Syria First death confirmed. UN ; Chile The United Nations issues a warning regarding the discovery of H1N1-infected turkeys on farms in Chile, an unusual case of zoonosis which raises concerns about possible increased genetic reassortment of the virus. WHO Most countries in the Southern Hemisphere (represented by Chile, Argentina, New Zealand, and Australia) appear to have passed their peak of influenza activity and returned to baseline activity. ECDC Based partially on data from the Southern Hemisphere, the ECDC forecasts a first wave of infections in autumn and winter which stresses hospitals in particular; it is noted, however, that "the overall interruption of essential services in (well-prepared) countries has been manageable". Germany 15,567 H1N1 cases confirmed. Bangladesh First death confirmed. Brazil 602 H1N1 deaths confirmed, the highest number of any nation-state to date. United States CDC FluView Week 34: Influenza activity, which had been largely stable or decreasing in prior weeks, increases in the U.S. "Six states and Puerto Rico reported geographically widespread influenza activity, 13 states reported regional influenza activity, 10 states and the District of Columbia reported local influenza activity, 19 states reported sporadic influenza activity, two states reported no influenza activity, and Guam and the U.S. Virgin Islands did not report." Furthermore, Region IV, i.e. the Southeast, reports increased out-patient ILI above its regional baseline. WHO At least 2,837 deaths worldwide are reported. Colombia President Álvaro Uribe is confirmed to have swine flu, the second Head of state known to have been infected. Djibouti First seven cases confirmed. United Arab Emirates Second death confirmed, that of a thirty-year-old Pakistani expatriate who died following Caesarian section . Argentina The most H1N1 deaths per capita . Bahrain First death confirmed, a South East Asian woman in her thirties with underyling medical conditions. Sweden First death confirmed. Australia First case of reverse zoonosis confirmed in a piggery in Dunedoo . United States CDC FluView Week 30: Widespread influenza activity in four states, regional activity in 11. "Over 98% of all subtyped influenza A viruses being reported to CDC were novel influenza A (H1N1) viruses." South Africa First confirmed death in South Africa. Total number of deaths at end of epidemic 93. [ citation needed ]India First death confirmed. Netherlands First death confirmed, that of a 17-year-old male. Solomon Islands First case confirmed. WHO 1,462 deaths worldwide are reported. United States CDC FluView Week 31: Widespread influenza activity in four states, regional activity in 10. Costa Rica President Óscar Arias is confirmed to have swine flu, the first head of state known to have been infected. WHO 1,799 deaths worldwide are reported. Madagascar First case confirmed. Democratic Republic of the Congo First H1N1 case confirmed. United States CDC FluView Week 32: Widespread influenza activity in two states, regional activity in eight. Malaysia Two more deaths confirmed. Total: 64 deaths. Malta First death confirmed. Malaysia Three more deaths confirmed. Total: 67 deaths. Belarus First H1N1 case confirmed. [ citation needed ]Kuwait First death confirmed. Malaysia One more death confirmed. Total: 68 deaths. The unusually high reported death rate, four times the global average, is investigated by the WHO. Netherlands Second death confirmed, that of a 58-year-old male. Chile H1N1 is found in turkeys on farms in Chile near the port city of Valparaiso in a unique zoonosis cluster. Germany 13,740 A(H1N1) cases confirmed. Oman First death confirmed. United Arab Emirates First death confirmed. United Kingdom First death confirmed in Northern Ireland, that of woman with underlying health conditions. New Caledonia First death confirmed. United States CDC FluView Week 33: Widespread influenza activity in two states, regional activity in 13. Activity appears to be increasing in the Southeast. WHO At least 2,185 deaths worldwide are reported. Greece First death confirmed. Germany 14,325 H1N1 cases confirmed. Kyrgyzstan First two cases confirmed, that of a husband and wife; the man had recently traveled to Dubai. Malaysia One more death confirmed. Total: 69 deaths. Malaysia One more death confirmed. Total: 70 deaths. Angola First case confirmed. Germany 14,940 H1N1 cases confirmed. Iran First death confirmed [ citation needed ] Malaysia One more death confirmed. Total: 71 deaths. Syria First death confirmed. UN ; Chile The United Nations issues a warning regarding the discovery of H1N1-infected turkeys on farms in Chile, an unusual case of zoonosis which raises concerns about possible increased genetic reassortment of the virus. WHO Most countries in the Southern Hemisphere (represented by Chile, Argentina, New Zealand, and Australia) appear to have passed their peak of influenza activity and returned to baseline activity. ECDC Based partially on data from the Southern Hemisphere, the ECDC forecasts a first wave of infections in autumn and winter which stresses hospitals in particular; it is noted, however, that "the overall interruption of essential services in (well-prepared) countries has been manageable". Germany 15,567 H1N1 cases confirmed. Bangladesh First death confirmed. Brazil 602 H1N1 deaths confirmed, the highest number of any nation-state to date. United States CDC FluView Week 34: Influenza activity, which had been largely stable or decreasing in prior weeks, increases in the U.S. "Six states and Puerto Rico reported geographically widespread influenza activity, 13 states reported regional influenza activity, 10 states and the District of Columbia reported local influenza activity, 19 states reported sporadic influenza activity, two states reported no influenza activity, and Guam and the U.S. Virgin Islands did not report." Furthermore, Region IV, i.e. the Southeast, reports increased out-patient ILI above its regional baseline. WHO At least 2,837 deaths worldwide are reported. Colombia President Álvaro Uribe is confirmed to have swine flu, the second Head of state known to have been infected. Djibouti First seven cases confirmed. United Arab Emirates Second death confirmed, that of a thirty-year-old Pakistani expatriate who died following Caesarian section . Argentina The most H1N1 deaths per capita . Bahrain First death confirmed, a South East Asian woman in her thirties with underyling medical conditions. Sweden First death confirmed. Macau First death confirmed. Portugal 5,123 cases officially confirmed Malaysia One more death confirmed. Total: 73 deaths. Norway First death confirmed. United States The CDC in its Morbidity and Mortality Weekly Report notes that 67% of thirty-six children who have died from H1N1 early in the epidemic had at least one serious chronic medical condition, with neurodevelopmental conditions such as developmental delay, epilepsy, and cerebral palsy being especially prominent. Roughly one in thirteen deaths have been of school-age children. More than 80% of the children who died were five or older, in contrast with the seasonal flu baseline of half or more of the influenza fatalities being four or younger. Italy First death confirmed. United States CDC FluView Week 35: Influenza increases in the U.S. with widespread influenza activity in 11 states and regional activity in 13; the proportion of outpatient visits for influenza-like illness (ILI) is above the national baseline, with four out of ten HHS Surveillance Regions reporting ILI above region-specific baselines. "97% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,205 deaths worldwide are reported. Ecuador Ecuador's chief of presidential security, Col. John Merino, dies of H1N1 flu after twenty-eight days at Quito Military Hospital. Faroe Islands First 44 cases confirmed. Namibia First death confirmed, that of a 37-year-old businessman who had fallen ill in Angola. Suriname First death confirmed. Madagascar First death confirmed. USA An outbreak is confirmed at the gaming convention PAX in Seattle, Washington. Malawi First case confirmed. Australia First case of Oseltamivir (Tamiflu) resistance found. United States CDC FluView Week 36: Influenza activity continues to increase with widespread influenza activity in twenty-one states, regional influenza activity in nine. Seven of ten HHS Surveillance Regions report ILI activity above region-specific baselines. "99% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,486 deaths worldwide are reported. Mozambique First death confirmed, that of a 29-year-old female with an unspecified chronic illness. Malta Third death confirmed. Netherlands The third and fourth deaths are confirmed, that of a 52-year-old man and an 85-year-old woman, respectively, both of whom had underlying medical conditions. United Kingdom Health Minister Andy Burnham states that the second peak of swine flu has started as 5,000 people contracted the virus this week, compared to 3,000 the week before. Martinique First death confirmed, that of an 18-month-old girl. Malaysia One more death confirmed. Total: 77 deaths. United States CDC FluView Week 37: Widespread influenza activity in twenty-six states, regional activity in 11. All of the HHS ILI regions report elevated levels of influenza activity above their region-specific baselines except for Region I (New England). WHO Over 3,917 deaths worldwide are reported. China A national vaccination campaign begins in China, making it the first country to issue the H1N1 vaccine. United States The U.S. government orders a total of 251 million doses of H1N1 vaccine from manufacturers, up from the long-planned total of 195 million. Portugal The first death confirmed, that of a Portuguese man living in France. Germany First death confirmed, that of a 36-year-old woman who died of a so-called superinfection which included H1N1. United States Forty-two schools are closed in eight states as the second wave of the pandemic begins in early autumn. United States CDC FluView Week 38: Widespread influenza activity in twenty-seven states, regional activity in 18. WHO At least 4,108 deaths worldwide are reported. United States The second wave of the H1N1 pandemic begins to stress hospitals in the U.S. and prompts some school closures. Cambodia First death confirmed, in Phnom Penh. Ireland First case of reverse zoonosis in pigs. Australia Mass vaccination drive begins, the second in the world. Bulgaria First death confirmed. China Sinovac Biotech Ltd., the first company worldwide to complete clinical trials for a vaccine, receives an order for an additional 3 million doses of H1N1 vaccine from the PRC government, making for a total of 6.3 million doses. United States 46 states and Washington, D.C. begin ordering what becomes by the next day a cumulative total of 1,378,200 doses of the nasal-spray Live Attenuated Influenza Vaccine ( LAIV ) for H1N1.Macau First death confirmed. Portugal 5,123 cases officially confirmed Malaysia One more death confirmed. Total: 73 deaths. Norway First death confirmed. United States The CDC in its Morbidity and Mortality Weekly Report notes that 67% of thirty-six children who have died from H1N1 early in the epidemic had at least one serious chronic medical condition, with neurodevelopmental conditions such as developmental delay, epilepsy, and cerebral palsy being especially prominent. Roughly one in thirteen deaths have been of school-age children. More than 80% of the children who died were five or older, in contrast with the seasonal flu baseline of half or more of the influenza fatalities being four or younger. Italy First death confirmed. United States CDC FluView Week 35: Influenza increases in the U.S. with widespread influenza activity in 11 states and regional activity in 13; the proportion of outpatient visits for influenza-like illness (ILI) is above the national baseline, with four out of ten HHS Surveillance Regions reporting ILI above region-specific baselines. "97% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,205 deaths worldwide are reported. Ecuador Ecuador's chief of presidential security, Col. John Merino, dies of H1N1 flu after twenty-eight days at Quito Military Hospital. Faroe Islands First 44 cases confirmed. Namibia First death confirmed, that of a 37-year-old businessman who had fallen ill in Angola. Suriname First death confirmed. Madagascar First death confirmed. USA An outbreak is confirmed at the gaming convention PAX in Seattle, Washington. Malawi First case confirmed. Australia First case of Oseltamivir (Tamiflu) resistance found. United States CDC FluView Week 36: Influenza activity continues to increase with widespread influenza activity in twenty-one states, regional influenza activity in nine. Seven of ten HHS Surveillance Regions report ILI activity above region-specific baselines. "99% of all subtyped influenza A viruses being reported to CDC were 2009 influenza A (H1N1) viruses." WHO At least 3,486 deaths worldwide are reported. Mozambique First death confirmed, that of a 29-year-old female with an unspecified chronic illness. Malta Third death confirmed. Netherlands The third and fourth deaths are confirmed, that of a 52-year-old man and an 85-year-old woman, respectively, both of whom had underlying medical conditions. United Kingdom Health Minister Andy Burnham states that the second peak of swine flu has started as 5,000 people contracted the virus this week, compared to 3,000 the week before. Martinique First death confirmed, that of an 18-month-old girl. Malaysia One more death confirmed. Total: 77 deaths. United States CDC FluView Week 37: Widespread influenza activity in twenty-six states, regional activity in 11. All of the HHS ILI regions report elevated levels of influenza activity above their region-specific baselines except for Region I (New England). WHO Over 3,917 deaths worldwide are reported. China A national vaccination campaign begins in China, making it the first country to issue the H1N1 vaccine. United States The U.S. government orders a total of 251 million doses of H1N1 vaccine from manufacturers, up from the long-planned total of 195 million. Portugal The first death confirmed, that of a Portuguese man living in France. Germany First death confirmed, that of a 36-year-old woman who died of a so-called superinfection which included H1N1. United States Forty-two schools are closed in eight states as the second wave of the pandemic begins in early autumn. United States CDC FluView Week 38: Widespread influenza activity in twenty-seven states, regional activity in 18. WHO At least 4,108 deaths worldwide are reported. United States The second wave of the H1N1 pandemic begins to stress hospitals in the U.S. and prompts some school closures. Cambodia First death confirmed, in Phnom Penh. Ireland First case of reverse zoonosis in pigs. Australia Mass vaccination drive begins, the second in the world. Bulgaria First death confirmed. China Sinovac Biotech Ltd., the first company worldwide to complete clinical trials for a vaccine, receives an order for an additional 3 million doses of H1N1 vaccine from the PRC government, making for a total of 6.3 million doses. United States 46 states and Washington, D.C. begin ordering what becomes by the next day a cumulative total of 1,378,200 doses of the nasal-spray Live Attenuated Influenza Vaccine ( LAIV ) for H1N1.United States CDC FluView Week 39: The proportion of deaths attributed to pneumonia and influenza (P&I) reaches the epidemic threshold with eight out of ten HHS ILI regions reporting region-specific ILI activity above region-specific baseline levels. Widespread influenza activity in thirty-seven states, regional activity in 11. WHO At least 4,525 deaths worldwide are reported. Tajikistan First case confirmed. United States The CDC's 2009–10 influenza season officially begins. United Nations Rich countries should make more vaccines available to poorer nations where the H1N1 virus is starting to hit, United Nations health officials said. They said increased readiness for swine flu was needed in developing countries with weaker medical systems and with large, young populations, who are most vulnerable to the disease. Some countries, such as the United States, Brazil and France, have agreed to make 10 percent of their national vaccine stockpile available to developing countries. Manufacturers have also donated about 150 million doses of vaccine. China First death confirmed, in Lhasa , Tibet . Tanzania First death confirmed. Yemen Tamiflu resistance found. Cuba First deaths confirmed, that of three pregnant women. United States CDC FluView Week 40: The proportion of deaths attributed to pneumonia and influenza (P&I) is officially above the epidemic threshold. Moreover, for the first time all 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-one states, and regional activity in eight, with only one state—Hawaii—reporting local influenza activity. WHO At least 4,735 deaths worldwide are reported. Norway first case of reverse zoonosis detected in Nord-Trøndelag . Rwanda First cases confirmed. São Tomé and Príncipe First cases confirmed. Sweden Mass vaccination begins. Vietnam Three cases of Tamiflu resistance (which developed during hospital treatment) are confirmed. The resistant strains were apparently not transmitted, and all three patients survived. Mongolia First cases confirmed. India Six more deaths confirmed. Total: 405 deaths. Trinidad and Tobago First death confirmed. United Kingdom The death toll passes 100. Total confirmed deaths: 106. The NHS confirms that second wave of swine flu has begun, with cases in Wales and Northern Ireland being especially high. The Minister of Health confirms that there were 27,000 cases in the last week in England alone, up from 14,000 the week before. The Minister of Health also announced that 415,000 H1N1 vaccinations shall take place on the week beginging 21 October, then 5,000,000 more vaccinations the week after. 20% of all hospitalized cases are now critical, up from 12% the week before. The government believes it can get 50,000,000 Britons vaccinated before Christmas. United States An initial shortfall of swine flu vaccine is predicted shortly after the proportion of deaths attributed to pneumonia and influenza goes above the epidemic threshold in some states, with flu activity widespread in 41 states. It is also announced that the number cases, hospitalizations and deaths are unprecedented for this time of year, with flu-like illnesses accounting for 6.1% of all doctor visits, itself an unusually high number. WHO At least 4,999 deaths worldwide are reported. China Second death confirmed, in the northwestern province of Qinghai . United States CDC FluView Week 41: All 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-six states, regional activity in three. United States H1N1 is confirmed in a nasal mucus sample taken from a show hog at the Minnesota State Fair in the first case of zoonosis in the country. India Two more deaths confirmed. Total: 415 deaths. Japan Mass vaccinations begin. Canada H1N1-infected turkeys are confirmed in Ontario, the second such case of zoonosis reported in the world. Iceland First death confirmed. United States In a unique case of zoonosis, a pet ferret in Oregon is confirmed to be infected with H1N1. Canada A turkey farm in Ontario province has been confirmed infected with A/H1N1 flu, making Canada the second country to report such infection after Chile, health officials confirmed Japan Ten H1N1-infected pigs are discovered in a swine herd in Osaka Prefecture, the first reported case of zoonosis in Asia. UK H1N1 vaccinations begin nationwide, with 14,000,000 high-priority people with conditions such as asthma to be vaccinated initially, then eventually up to 51,000,000 other Britons. Serbia First death confirmed. Czech Republic First death confirmed. Iraq Fears over the H1N1 virus prompts nearly 2,500 school closures. Germany Third H1N1 death confirmed. Mongolia First death confirmed. Netherlands Two new deaths reported, that of a 14-year-old girl and 40-year-old man. Total deaths: 6. United States President Barack Obama declares a national emergency , stating "The potential exists for the pandemic to overburden health care resources in some localities." United States Various public health departments across the country run out of the H1N1 vaccine, due to the shortfall of 10 million doses as the national vaccination campaign gets underway in earnest; 40 million doses had initially been projected. According to the CDC's FluView Week 42, influenza activity is widespread in 48 states, with regional activity in just two: Hawaii and South Carolina. WHO At least 5,712 deaths worldwide are reported. China Another death confirmed, in the northwestern province of Xinjiang . Oman Mass vaccinations begin. Canada Canada's H1N1 vaccination campaign begins. Russia First two deaths confirmed, in the far eastern city of Chita . Iceland First case of reverse zoonosis detected in pigs. Portugal A ten-year-old dies 48 hours after contracting the flu. Afghanistan First death confirmed. Nigeria First case confirmed. Republic of Congo First case confirmed. ECDC The European Centre for Disease Control reports a total of 302 fatal cases in Europe to date; all of the 27 EU and the four EFTA countries are reporting cases of pandemic (H1N1) 2009 influenza. Ukraine First death confirmed. Meanwhile, Ukrainian Prime Minister Yulia Tymoshenko ordered a massive and for Ukraine unprecedented disease-control programme to go into effect immediately in an attempt to prevent the spread of the disease. A 'full quarantine' will be imposed in seven provinces of Western Ukraine , with police monitoring the entrance and exit of all persons. It will block those lacking justification for travel Croatia First death confirmed. United States According to the CDC's FluView Week 43, influenza activity is widespread in 48 states, with regional activity in two: Hawaii and Mississippi. United States CDC FluView Week 39: The proportion of deaths attributed to pneumonia and influenza (P&I) reaches the epidemic threshold with eight out of ten HHS ILI regions reporting region-specific ILI activity above region-specific baseline levels. Widespread influenza activity in thirty-seven states, regional activity in 11. WHO At least 4,525 deaths worldwide are reported. Tajikistan First case confirmed. United States The CDC's 2009–10 influenza season officially begins. United Nations Rich countries should make more vaccines available to poorer nations where the H1N1 virus is starting to hit, United Nations health officials said. They said increased readiness for swine flu was needed in developing countries with weaker medical systems and with large, young populations, who are most vulnerable to the disease. Some countries, such as the United States, Brazil and France, have agreed to make 10 percent of their national vaccine stockpile available to developing countries. Manufacturers have also donated about 150 million doses of vaccine. China First death confirmed, in Lhasa , Tibet . Tanzania First death confirmed.Yemen Tamiflu resistance found. Cuba First deaths confirmed, that of three pregnant women. United States CDC FluView Week 40: The proportion of deaths attributed to pneumonia and influenza (P&I) is officially above the epidemic threshold. Moreover, for the first time all 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-one states, and regional activity in eight, with only one state—Hawaii—reporting local influenza activity. WHO At least 4,735 deaths worldwide are reported. Norway first case of reverse zoonosis detected in Nord-Trøndelag . Rwanda First cases confirmed. São Tomé and Príncipe First cases confirmed. Sweden Mass vaccination begins. Vietnam Three cases of Tamiflu resistance (which developed during hospital treatment) are confirmed. The resistant strains were apparently not transmitted, and all three patients survived. Mongolia First cases confirmed. India Six more deaths confirmed. Total: 405 deaths. Trinidad and Tobago First death confirmed. United Kingdom The death toll passes 100. Total confirmed deaths: 106. The NHS confirms that second wave of swine flu has begun, with cases in Wales and Northern Ireland being especially high. The Minister of Health confirms that there were 27,000 cases in the last week in England alone, up from 14,000 the week before. The Minister of Health also announced that 415,000 H1N1 vaccinations shall take place on the week beginging 21 October, then 5,000,000 more vaccinations the week after. 20% of all hospitalized cases are now critical, up from 12% the week before. The government believes it can get 50,000,000 Britons vaccinated before Christmas. United States An initial shortfall of swine flu vaccine is predicted shortly after the proportion of deaths attributed to pneumonia and influenza goes above the epidemic threshold in some states, with flu activity widespread in 41 states. It is also announced that the number cases, hospitalizations and deaths are unprecedented for this time of year, with flu-like illnesses accounting for 6.1% of all doctor visits, itself an unusually high number. WHO At least 4,999 deaths worldwide are reported. China Second death confirmed, in the northwestern province of Qinghai . United States CDC FluView Week 41: All 10 HHS ILI regions reported ILI above region-specific baseline levels. Widespread influenza activity in forty-six states, regional activity in three. United States H1N1 is confirmed in a nasal mucus sample taken from a show hog at the Minnesota State Fair in the first case of zoonosis in the country. India Two more deaths confirmed. Total: 415 deaths. Japan Mass vaccinations begin. Canada H1N1-infected turkeys are confirmed in Ontario, the second such case of zoonosis reported in the world. Iceland First death confirmed. United States In a unique case of zoonosis, a pet ferret in Oregon is confirmed to be infected with H1N1. Canada A turkey farm in Ontario province has been confirmed infected with A/H1N1 flu, making Canada the second country to report such infection after Chile, health officials confirmed Japan Ten H1N1-infected pigs are discovered in a swine herd in Osaka Prefecture, the first reported case of zoonosis in Asia. UK H1N1 vaccinations begin nationwide, with 14,000,000 high-priority people with conditions such as asthma to be vaccinated initially, then eventually up to 51,000,000 other Britons. Serbia First death confirmed. Czech Republic First death confirmed. Iraq Fears over the H1N1 virus prompts nearly 2,500 school closures. Germany Third H1N1 death confirmed. Mongolia First death confirmed. Netherlands Two new deaths reported, that of a 14-year-old girl and 40-year-old man. Total deaths: 6. United States President Barack Obama declares a national emergency , stating "The potential exists for the pandemic to overburden health care resources in some localities." United States Various public health departments across the country run out of the H1N1 vaccine, due to the shortfall of 10 million doses as the national vaccination campaign gets underway in earnest; 40 million doses had initially been projected. According to the CDC's FluView Week 42, influenza activity is widespread in 48 states, with regional activity in just two: Hawaii and South Carolina. WHO At least 5,712 deaths worldwide are reported. China Another death confirmed, in the northwestern province of Xinjiang . Oman Mass vaccinations begin. Canada Canada's H1N1 vaccination campaign begins. Russia First two deaths confirmed, in the far eastern city of Chita . Iceland First case of reverse zoonosis detected in pigs. Portugal A ten-year-old dies 48 hours after contracting the flu. Afghanistan First death confirmed. Nigeria First case confirmed. Republic of Congo First case confirmed. ECDC The European Centre for Disease Control reports a total of 302 fatal cases in Europe to date; all of the 27 EU and the four EFTA countries are reporting cases of pandemic (H1N1) 2009 influenza. Ukraine First death confirmed. Meanwhile, Ukrainian Prime Minister Yulia Tymoshenko ordered a massive and for Ukraine unprecedented disease-control programme to go into effect immediately in an attempt to prevent the spread of the disease. A 'full quarantine' will be imposed in seven provinces of Western Ukraine , with police monitoring the entrance and exit of all persons. It will block those lacking justification for travel Croatia First death confirmed. United States According to the CDC's FluView Week 43, influenza activity is widespread in 48 states, with regional activity in two: Hawaii and Mississippi. Afghanistan Schools are closed for three weeks after the first H1N1 death is recorded. Kuwait Mass vaccinations begin. Morocco Mass vaccinations begin. Turkey Mass vaccinations begin. WHO At least 6,071 deaths worldwide are reported. Austria First death confirmed. Belarus First death confirmed. Egypt Mass vaccinations begin. Qatar Mass vaccinations begin. Slovenia First death confirmed. US The USDA reports the first H1N1 zoonosis in commercial swine, in a herd in Indiana. Netherlands First case of Oseltamivir (Tamiflu) resistance found. United States The first case in the world of H1N1 zoonosis in a cat is confirmed, in Iowa. San Marino First case confirmed. Bulgaria A nationwide epidemic is declared. Hong Kong Reverse zoonosis is detected in two slaughtered pigs. Bahrain Mass vaccinations begin. Belgium Mass vaccination begins. Saudi Arabia Mass vaccinations begin. United States CDC FluView Week 44: Widespread influenza activity in forty-six state, regional activity in four. "The proportion of outpatient visits for influenza-like illness (ILI) was 6.7% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Pakistan First death confirmed. Sri Lanka First death confirmed. Latvia First death confirmed. United Arab Emirates Mass vaccinations begin. Greenland First case confirmed. Burundi First case confirmed. Armenia First two cases confirmed. France Mass vaccination drive begins. WHO In its 74th update, the WHO reports early signs that the early flu season has peaked in North America, even as the pandemic intensifies across much of Europe and Central and Eastern Asia. Bulgaria Health authorities confirm more than 12 people have died from H1N1 within a week; the latest victim is a 28-year-old man who died from respiratory failure. Cyprus First death confirmed. Kosovo First death confirmed. Poland First death confirmed. United States CDC FluView Week 45: Widespread influenza activity in forty-three states, regional activity in seven. "The proportion of outpatient visits for influenza-like illness (ILI) was 5.5% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Tunisia First confirmed deaths. Somalia First case confirmed. Bosnia & Herzegovina First death confirmed. North Korea First case confirmed. Morocco First confirmed deaths. Cyprus Mass vaccinations begin. Hungary National epidemic declared. Lithuania First death confirmed. Macedonia First death confirmed. United States First feline death confirmed, in the state of Oregon. Maldives First death confirmed. Denmark First death confirmed. Jordan Mass vaccinations begin. Norway A potentially significant mutation is found in specimens taken of the H1N1 virus taken from two fatalities; a third victim was seriously ill. UK The first person-to-person transmission of Tamiflu-resistant H1N1 in the world is confirmed at the University Hospital of Wales in Cardiff . Five patients are so infected, with three apparently having been infected in hospital in a case of iatrogenic transmission. US An iatrogenic Tamiflu-resistant cluster is reported at Duke University Medical Center in North Carolina, with four severely ill cancer patients infected, the largest cluster in the U.S. More than fifty resistant cases have been reported in the world since April. United States CDC FluView Week 46: Widespread influenza activity in thirty-two states, regional activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 4.3% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels. Romania First death confirmed, that of a 43-year-old man with obesity, high blood pressure, and diabetes. United States First double infection case confirmed, in a pediatrician in West Virginia. [ citation needed ] Montserrat First case confirmed. WHO H1N1 mutations have led to roughly 75 people worldwide developing Tamiflu resistance. Furthermore, the separate D222G or D225G mutation which helps the virus to reach deep into the lungs has been reported in cases both severe and mild in Norway, Ukraine, Brazil, China, Japan, Mexico and the United States. France The H1N1 mutation first detected in Norway causes two deaths in separate French cities. South Korea First double infection case confirmed, in a two-year-old girl. China Two cases in dogs are confirmed, the first instance of canine zoonosis in the world. Indonesia First case in pigs is confirmed, in southwest Sulawesi. United States CDC FluView Week 47: Widespread influenza activity, in Twenty-five states, regional influenza activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 3.7% which is above the national baseline of 2.3%. Eight of the 10 regions reported ILI at or above region-specific baseline levels. Regions 6 and 10 reported ILI below their region specific baselines." United States The CDC states that H1N1 may have peaked as the number of states reporting widespread influenza dropped from 43 the previous week to 32 this week. Furthermore, influenza-like illness now account for 4.3% of doctor visits, down from 8% four weeks ago (on average, influenza accounts for 2.5% of doctor visits). The proportion of deaths attributed to pneumonia and influenza continues to be higher than expected for this time of year, however. This proportion has remained elevated for eight weeks now. Finland First case of reverse zoonosis in pigs. Libya First death confirmed. Afghanistan Schools are closed for three weeks after the first H1N1 death is recorded. Kuwait Mass vaccinations begin. Morocco Mass vaccinations begin. Turkey Mass vaccinations begin. WHO At least 6,071 deaths worldwide are reported. Austria First death confirmed. Belarus First death confirmed. Egypt Mass vaccinations begin. Qatar Mass vaccinations begin. Slovenia First death confirmed. US The USDA reports the first H1N1 zoonosis in commercial swine, in a herd in Indiana. Netherlands First case of Oseltamivir (Tamiflu) resistance found. United States The first case in the world of H1N1 zoonosis in a cat is confirmed, in Iowa. San Marino First case confirmed. Bulgaria A nationwide epidemic is declared. Hong Kong Reverse zoonosis is detected in two slaughtered pigs. Bahrain Mass vaccinations begin. Belgium Mass vaccination begins. Saudi Arabia Mass vaccinations begin. United States CDC FluView Week 44: Widespread influenza activity in forty-six state, regional activity in four. "The proportion of outpatient visits for influenza-like illness (ILI) was 6.7% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Pakistan First death confirmed. Sri Lanka First death confirmed. Latvia First death confirmed. United Arab Emirates Mass vaccinations begin. Greenland First case confirmed. Burundi First case confirmed.Armenia First two cases confirmed. France Mass vaccination drive begins. WHO In its 74th update, the WHO reports early signs that the early flu season has peaked in North America, even as the pandemic intensifies across much of Europe and Central and Eastern Asia. Bulgaria Health authorities confirm more than 12 people have died from H1N1 within a week; the latest victim is a 28-year-old man who died from respiratory failure. Cyprus First death confirmed. Kosovo First death confirmed. Poland First death confirmed. United States CDC FluView Week 45: Widespread influenza activity in forty-three states, regional activity in seven. "The proportion of outpatient visits for influenza-like illness (ILI) was 5.5% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels." Tunisia First confirmed deaths. Somalia First case confirmed. Bosnia & Herzegovina First death confirmed. North Korea First case confirmed. Morocco First confirmed deaths. Cyprus Mass vaccinations begin.Hungary National epidemic declared. Lithuania First death confirmed. Macedonia First death confirmed. United States First feline death confirmed, in the state of Oregon. Maldives First death confirmed. Denmark First death confirmed. Jordan Mass vaccinations begin. Norway A potentially significant mutation is found in specimens taken of the H1N1 virus taken from two fatalities; a third victim was seriously ill. UK The first person-to-person transmission of Tamiflu-resistant H1N1 in the world is confirmed at the University Hospital of Wales in Cardiff . Five patients are so infected, with three apparently having been infected in hospital in a case of iatrogenic transmission. US An iatrogenic Tamiflu-resistant cluster is reported at Duke University Medical Center in North Carolina, with four severely ill cancer patients infected, the largest cluster in the U.S. More than fifty resistant cases have been reported in the world since April. United States CDC FluView Week 46: Widespread influenza activity in thirty-two states, regional activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 4.3% which is above the national baseline of 2.3%. All 10 regions reported ILI above region-specific baseline levels. Romania First death confirmed, that of a 43-year-old man with obesity, high blood pressure, and diabetes. United States First double infection case confirmed, in a pediatrician in West Virginia. [ citation needed ] Montserrat First case confirmed. WHO H1N1 mutations have led to roughly 75 people worldwide developing Tamiflu resistance. Furthermore, the separate D222G or D225G mutation which helps the virus to reach deep into the lungs has been reported in cases both severe and mild in Norway, Ukraine, Brazil, China, Japan, Mexico and the United States. France The H1N1 mutation first detected in Norway causes two deaths in separate French cities. South Korea First double infection case confirmed, in a two-year-old girl. China Two cases in dogs are confirmed, the first instance of canine zoonosis in the world. Indonesia First case in pigs is confirmed, in southwest Sulawesi. United States CDC FluView Week 47: Widespread influenza activity, in Twenty-five states, regional influenza activity in 17. "The proportion of outpatient visits for influenza-like illness (ILI) was 3.7% which is above the national baseline of 2.3%. Eight of the 10 regions reported ILI at or above region-specific baseline levels. Regions 6 and 10 reported ILI below their region specific baselines." United States The CDC states that H1N1 may have peaked as the number of states reporting widespread influenza dropped from 43 the previous week to 32 this week. Furthermore, influenza-like illness now account for 4.3% of doctor visits, down from 8% four weeks ago (on average, influenza accounts for 2.5% of doctor visits). The proportion of deaths attributed to pneumonia and influenza continues to be higher than expected for this time of year, however. This proportion has remained elevated for eight weeks now. Finland First case of reverse zoonosis in pigs. Libya First death confirmed. Saudi Arabia Only five deaths and 73 cases are reported from the hajj . United Kingdom First case of reverse zoonosis in pigs is discovered, in Norfolk . US CDC FluView Week 48: Widespread flu activity in 14 states, regional activity in 25. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the tenth consecutive week. The proportion of outpatient visits for influenza-like illness (ILI) was 2.7% which is above the national baseline of 2.3%." Gaza Strip First five cases are confirmed in the blockaded Gaza Strip . Japan 100 fatalities confirmed. United States With one in six Americans infected, or 15% of the country, nearly 10,000 have died to date, including 1,100 children and 7,500 younger adults. More than 200,000 Americans had been hospitalized to date — roughly the same number who are so affected by the regular seasonal flu variant in an entire year. Furthermore, with 12 million additional doses of H1N1 vaccine being released this week, several states begin to distribute the vaccine to the general public. North Korea First deaths are confirmed, according to newsletters released by the Seoul-based aid group Good Friends. United States A sophisticated Bayesian analysis of public health data from April to the end of June from New York City and Milwaukee indicates that the pandemic's symptomatic case-fatality ratio has been far lower than the previous three pandemics of 1968, 1957, and 1918, making it to date the mildest pandemic on record. Afghanistan The 17th H1N1 fatality is reported. Gaza The eighth fatality is reported, that of a child with underlying kidney failure, within a week of the first H1N1 case in the Gaza Strip. United States CDC FluView Week 49: Widespread influenza activity in 11 states, regional activity in twenty. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the eleventh consecutive week... The proportion of outpatient visits for influenza-like illness (ILI) was 2.6% which is above the national baseline of 2.3%. Five of the 10 regions reported ILI at or above region-specific baseline levels." Georgia First fatality confirmed, that of a 27-year-old man. [ citation needed ] Qatar Mass vaccinations begin. United States Roughly 100 million H1N1 vaccines become widely available to the general public in pharmacies in several American states as the supply increases and restrictions to high-risk groups are lifted. Thailand First confirmed case of H1N1 in a pig, in a case of reverse zoonosis in Saraburi Province. The pig recovered. United States CDC FluView Week 50: The CDC reports that levels of influenza are declining steadily, with only seven states reporting widespread influenza activity and 18 reporting regional activity; furthermore, the proportion of deaths attributed to pneumonia and influenza (P&I) is below the epidemic threshold. The CDC also notes that almost all isolates of H1N1 remain sensitive to oseltamivir . "The proportion of outpatient visits for influenza-like illness (ILI) was 2.3% which is at the national baseline of 2.3%." US First case of canine zoonosis confirmed. The 13-year-old dog from New York state was believed to have contracted the virus from his owner. US H1N1 is discovered at two North Carolina pig farms, making it the 10th state to identify the virus in animals. The swine caught the disease from infected workers and recovered after becoming moderately ill. Argentina An Argentine study published in the New England Journal of Medicine shows that "Pediatric 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza than in previous years," and that the elevated risk for pregnant women extends for as long as two weeks after they give birth. US CDC FluView Week 51: Influenza activity decreases slightly, although the proportion of deaths attributed to P&I remained above the epidemic threshold. "Four states reported geographically widespread influenza activity, 13 states reported regional influenza activity, the District of Columbia, Puerto Rico, and 19 states reported local influenza activity, Guam and 13 states reported sporadic influenza activity, and one state reported no influenza activity, the U.S. Virgin Islands did not report." WHO At least 12,220 deaths globally are formally confirmed. (By contrast, the WHO estimates that the seasonal flu kills from 250,000 to 300,000 people around the world each year.) Overall, the activity of the H1N1 pandemic has peaked. Nepal First death confirmed, that of a woman who suffered major organ failure. WHO In Geneva Dr. Margaret Chan , Director-General of the WHO, remarks in the context of the H5N1 bird flu virus that "The fact that the long overdue influenza pandemic is so moderate in its impact is probably the best health news of the decade" but that "No, the world is not ready for a pandemic to be caused by H5N1." Given that H1N1 could still mutate, however, the WHO shall continue to monitor the pandemic for six months to a year. She also said that it would take at least two years before a true death total is established. (Approximately 11,500 people are believed to have died in more than 200 countries.) A study published in the New England Journal of Medicine finds that "household contacts less than 18 years of age were twice as susceptible to an acute respiratory illness as were those 19 to 50 years of age, whereas contacts older than 50 years were less susceptible". A joint US-UK study shows that children are twice as likely as adults to catch H1N1. Saudi Arabia Only five deaths and 73 cases are reported from the hajj . United Kingdom First case of reverse zoonosis in pigs is discovered, in Norfolk . US CDC FluView Week 48: Widespread flu activity in 14 states, regional activity in 25. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the tenth consecutive week. The proportion of outpatient visits for influenza-like illness (ILI) was 2.7% which is above the national baseline of 2.3%." Gaza Strip First five cases are confirmed in the blockaded Gaza Strip . Japan 100 fatalities confirmed. United States With one in six Americans infected, or 15% of the country, nearly 10,000 have died to date, including 1,100 children and 7,500 younger adults. More than 200,000 Americans had been hospitalized to date — roughly the same number who are so affected by the regular seasonal flu variant in an entire year. Furthermore, with 12 million additional doses of H1N1 vaccine being released this week, several states begin to distribute the vaccine to the general public. North Korea First deaths are confirmed, according to newsletters released by the Seoul-based aid group Good Friends. United States A sophisticated Bayesian analysis of public health data from April to the end of June from New York City and Milwaukee indicates that the pandemic's symptomatic case-fatality ratio has been far lower than the previous three pandemics of 1968, 1957, and 1918, making it to date the mildest pandemic on record. Afghanistan The 17th H1N1 fatality is reported. Gaza The eighth fatality is reported, that of a child with underlying kidney failure, within a week of the first H1N1 case in the Gaza Strip. United States CDC FluView Week 49: Widespread influenza activity in 11 states, regional activity in twenty. "The proportion of deaths attributed to pneumonia and influenza (P&I) was above the epidemic threshold for the eleventh consecutive week... The proportion of outpatient visits for influenza-like illness (ILI) was 2.6% which is above the national baseline of 2.3%. Five of the 10 regions reported ILI at or above region-specific baseline levels." Georgia First fatality confirmed, that of a 27-year-old man. [ citation needed ] Qatar Mass vaccinations begin. United States Roughly 100 million H1N1 vaccines become widely available to the general public in pharmacies in several American states as the supply increases and restrictions to high-risk groups are lifted. Thailand First confirmed case of H1N1 in a pig, in a case of reverse zoonosis in Saraburi Province. The pig recovered. United States CDC FluView Week 50: The CDC reports that levels of influenza are declining steadily, with only seven states reporting widespread influenza activity and 18 reporting regional activity; furthermore, the proportion of deaths attributed to pneumonia and influenza (P&I) is below the epidemic threshold. The CDC also notes that almost all isolates of H1N1 remain sensitive to oseltamivir . "The proportion of outpatient visits for influenza-like illness (ILI) was 2.3% which is at the national baseline of 2.3%." US First case of canine zoonosis confirmed. The 13-year-old dog from New York state was believed to have contracted the virus from his owner. US H1N1 is discovered at two North Carolina pig farms, making it the 10th state to identify the virus in animals. The swine caught the disease from infected workers and recovered after becoming moderately ill. Argentina An Argentine study published in the New England Journal of Medicine shows that "Pediatric 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza than in previous years," and that the elevated risk for pregnant women extends for as long as two weeks after they give birth. US CDC FluView Week 51: Influenza activity decreases slightly, although the proportion of deaths attributed to P&I remained above the epidemic threshold. "Four states reported geographically widespread influenza activity, 13 states reported regional influenza activity, the District of Columbia, Puerto Rico, and 19 states reported local influenza activity, Guam and 13 states reported sporadic influenza activity, and one state reported no influenza activity, the U.S. Virgin Islands did not report." WHO At least 12,220 deaths globally are formally confirmed. (By contrast, the WHO estimates that the seasonal flu kills from 250,000 to 300,000 people around the world each year.) Overall, the activity of the H1N1 pandemic has peaked. Nepal First death confirmed, that of a woman who suffered major organ failure. WHO In Geneva Dr. Margaret Chan , Director-General of the WHO, remarks in the context of the H5N1 bird flu virus that "The fact that the long overdue influenza pandemic is so moderate in its impact is probably the best health news of the decade" but that "No, the world is not ready for a pandemic to be caused by H5N1." Given that H1N1 could still mutate, however, the WHO shall continue to monitor the pandemic for six months to a year. She also said that it would take at least two years before a true death total is established. (Approximately 11,500 people are believed to have died in more than 200 countries.) A study published in the New England Journal of Medicine finds that "household contacts less than 18 years of age were twice as susceptible to an acute respiratory illness as were those 19 to 50 years of age, whereas contacts older than 50 years were less susceptible". A joint US-UK study shows that children are twice as likely as adults to catch H1N1. United States CDC FluView Week 52: The proportion of deaths attributed to P&I falls below the epidemic threshold. No influenza activity is reported in Nebraska. "One state reported geographically widespread influenza activity, 12 states reported regional influenza activity, Puerto Rico, the District of Columbia, and 17 states reported local influenza activity, the U.S. Virgin Islands, Guam, 19 states reported sporadic influenza activity, and one state reported no influenza activity." United States The CDC reports that only Alabama reports widespread influenza activity. Mali First case confirmed. United States According to the CDC no states have reported widespread influenza activity. Bermuda First death confirmed. Chad First case confirmed. Nigeria First death confirmed. Mauritania First case confirmed. United States The weekly report released by the CDC states that H1N1 activity has either remained stable or decreased over the past week in nine out of the ten regions of the United States. Furthermore, the proportion of deaths attributed to pneumonia and influenza, which technically remains above the epidemic threshold, has declined over the past week. Senegal First case confirmed United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Niger First case confirmed United States According to the CDC, only four states have reported regional influenza activity: Mississippi, Alabama, Georgia, and South Carolina. United States According to the CDC, five states have reported regional influenza activity: Mississippi, Alabama, Georgia, South Carolina, and Maine. United States According to the CDC, only three states have reported regional influenza activity: Mississippi, Alabama, and Georgia. United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cuba Mass vaccination begins. United States The CDC Morbidity and Mortality Weekly Report states that inoculation rates varied, with the highest rates in New England and the lowest in the South. (E.g., roughly 39% of the population of Rhode Island is immunized vis-à -vis 13% that of Mississippi.) Among children Georgia had the lowest vaccination rate, with 21%; the state currently has the highest level of H1N1 flu activity. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cambodia Mass vaccinations begin. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Guinea First case confirmed. WHO An external panel advises against winding down the pandemic alert level until experts have tracked the southern hemisphere's traditional autumn and winter flu season. Accusations of undue influence from the pharmaceutical industry were also addressed. US According to the CDC, no states have reported either widespread or regional influenza activity, and four have reported local activity: Hawaii, Alabama, Georgia, and South Carolina. WHO Director-General Dr. Margaret Chan states that "It is still premature and too early for us to say we have come to an end of the pandemic influenza worldwide. It would be prudent and appropriate... to continue to monitor the evolution of this pandemic for the next six to 12 months," i.e. possibly into 2011. She also remarked that although the United States, Britain and Canada have passed through a second wave of H1N1, outbreaks in India, Egypt and elsewhere are intensifying, and reiterates that countries remain ill-prepared for a bird flu (H5N1) pandemic. More than 200 countries have now been affected by H1N1 with almost 12,000 confirmed deaths worldwide, although the vast majority of those infected recovered without special treatment. Philippines Mass vaccinations begin. WHO Director-General Dr. Margaret Chan states at the U.N.'s World Health Assembly that "We are just plain lucky ... This has been the case with the A/ H1N1 influenza pandemic... The virus did not mutate to a more lethal form. Cases of resistance to oseltamivir remained few and isolated. The vaccine closely matched circulating viruses and showed an excellent safety record," Chan said. "Emergency wards and intensive care units were often strained, few health systems were overwhelmed ... Schools closed, but borders remained open, and disruptions to travel and trade were far less severe than feared," she told delegates from the agency's 193 member states. "Had things gone wrong in any of these areas, we would have a very different agenda before us today," she added." US Researchers discover the mutation which had enabled the pandemic. WHO Director-General Margaret Chan officially declares the H1N1 pandemic over as countries are now seeing a mix of H1N1, H3N2, and B viruses, with some populaces displaying community-level immunity to H1N1 of 20% to 40%. Nevertheless, Angus Nicoll of the European Centre for Disease Prevention and Control urged health officials worldwide to "prepare for a new type of seasonal flu to appear in the near future that will combine elements of the pandemic A(H1N1) strain, and older A(H3N2) strain and several lesser strains". "Pandemics are unpredictable and prone to deliver surprises," Director-General Chan noted. United States CDC FluView Week 52: The proportion of deaths attributed to P&I falls below the epidemic threshold. No influenza activity is reported in Nebraska. "One state reported geographically widespread influenza activity, 12 states reported regional influenza activity, Puerto Rico, the District of Columbia, and 17 states reported local influenza activity, the U.S. Virgin Islands, Guam, 19 states reported sporadic influenza activity, and one state reported no influenza activity." United States The CDC reports that only Alabama reports widespread influenza activity. Mali First case confirmed. United States According to the CDC no states have reported widespread influenza activity. Bermuda First death confirmed. Chad First case confirmed. Nigeria First death confirmed. United States CDC FluView Week 52: The proportion of deaths attributed to P&I falls below the epidemic threshold. No influenza activity is reported in Nebraska. "One state reported geographically widespread influenza activity, 12 states reported regional influenza activity, Puerto Rico, the District of Columbia, and 17 states reported local influenza activity, the U.S. Virgin Islands, Guam, 19 states reported sporadic influenza activity, and one state reported no influenza activity." United States The CDC reports that only Alabama reports widespread influenza activity. Mali First case confirmed. United States According to the CDC no states have reported widespread influenza activity. Bermuda First death confirmed. Chad First case confirmed. Nigeria First death confirmed. Mauritania First case confirmed. United States The weekly report released by the CDC states that H1N1 activity has either remained stable or decreased over the past week in nine out of the ten regions of the United States. Furthermore, the proportion of deaths attributed to pneumonia and influenza, which technically remains above the epidemic threshold, has declined over the past week. Senegal First case confirmed United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Niger First case confirmed Mauritania First case confirmed. United States The weekly report released by the CDC states that H1N1 activity has either remained stable or decreased over the past week in nine out of the ten regions of the United States. Furthermore, the proportion of deaths attributed to pneumonia and influenza, which technically remains above the epidemic threshold, has declined over the past week. Senegal First case confirmed United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Niger First case confirmed United States According to the CDC, only four states have reported regional influenza activity: Mississippi, Alabama, Georgia, and South Carolina. United States According to the CDC, five states have reported regional influenza activity: Mississippi, Alabama, Georgia, South Carolina, and Maine. United States According to the CDC, only three states have reported regional influenza activity: Mississippi, Alabama, and Georgia. United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cuba Mass vaccination begins. United States The CDC Morbidity and Mortality Weekly Report states that inoculation rates varied, with the highest rates in New England and the lowest in the South. (E.g., roughly 39% of the population of Rhode Island is immunized vis-à -vis 13% that of Mississippi.) Among children Georgia had the lowest vaccination rate, with 21%; the state currently has the highest level of H1N1 flu activity. United States According to the CDC, only four states have reported regional influenza activity: Mississippi, Alabama, Georgia, and South Carolina. United States According to the CDC, five states have reported regional influenza activity: Mississippi, Alabama, Georgia, South Carolina, and Maine. United States According to the CDC, only three states have reported regional influenza activity: Mississippi, Alabama, and Georgia. United States According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cuba Mass vaccination begins. United States The CDC Morbidity and Mortality Weekly Report states that inoculation rates varied, with the highest rates in New England and the lowest in the South. (E.g., roughly 39% of the population of Rhode Island is immunized vis-à -vis 13% that of Mississippi.) Among children Georgia had the lowest vaccination rate, with 21%; the state currently has the highest level of H1N1 flu activity. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cambodia Mass vaccinations begin. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Guinea First case confirmed. WHO An external panel advises against winding down the pandemic alert level until experts have tracked the southern hemisphere's traditional autumn and winter flu season. Accusations of undue influence from the pharmaceutical industry were also addressed. US According to the CDC, no states have reported either widespread or regional influenza activity, and four have reported local activity: Hawaii, Alabama, Georgia, and South Carolina. WHO Director-General Dr. Margaret Chan states that "It is still premature and too early for us to say we have come to an end of the pandemic influenza worldwide. It would be prudent and appropriate... to continue to monitor the evolution of this pandemic for the next six to 12 months," i.e. possibly into 2011. She also remarked that although the United States, Britain and Canada have passed through a second wave of H1N1, outbreaks in India, Egypt and elsewhere are intensifying, and reiterates that countries remain ill-prepared for a bird flu (H5N1) pandemic. More than 200 countries have now been affected by H1N1 with almost 12,000 confirmed deaths worldwide, although the vast majority of those infected recovered without special treatment. Philippines Mass vaccinations begin. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Cambodia Mass vaccinations begin. US According to the CDC, only three states have reported regional influenza activity: Alabama, Georgia, and South Carolina. Guinea First case confirmed. WHO An external panel advises against winding down the pandemic alert level until experts have tracked the southern hemisphere's traditional autumn and winter flu season. Accusations of undue influence from the pharmaceutical industry were also addressed. US According to the CDC, no states have reported either widespread or regional influenza activity, and four have reported local activity: Hawaii, Alabama, Georgia, and South Carolina. WHO Director-General Dr. Margaret Chan states that "It is still premature and too early for us to say we have come to an end of the pandemic influenza worldwide. It would be prudent and appropriate... to continue to monitor the evolution of this pandemic for the next six to 12 months," i.e. possibly into 2011. She also remarked that although the United States, Britain and Canada have passed through a second wave of H1N1, outbreaks in India, Egypt and elsewhere are intensifying, and reiterates that countries remain ill-prepared for a bird flu (H5N1) pandemic. More than 200 countries have now been affected by H1N1 with almost 12,000 confirmed deaths worldwide, although the vast majority of those infected recovered without special treatment. Philippines Mass vaccinations begin. WHO Director-General Dr. Margaret Chan states at the U.N.'s World Health Assembly that "We are just plain lucky ... This has been the case with the A/ H1N1 influenza pandemic... The virus did not mutate to a more lethal form. Cases of resistance to oseltamivir remained few and isolated. The vaccine closely matched circulating viruses and showed an excellent safety record," Chan said. "Emergency wards and intensive care units were often strained, few health systems were overwhelmed ... Schools closed, but borders remained open, and disruptions to travel and trade were far less severe than feared," she told delegates from the agency's 193 member states. "Had things gone wrong in any of these areas, we would have a very different agenda before us today," she added." WHO Director-General Dr. Margaret Chan states at the U.N.'s World Health Assembly that "We are just plain lucky ... This has been the case with the A/ H1N1 influenza pandemic... The virus did not mutate to a more lethal form. Cases of resistance to oseltamivir remained few and isolated. The vaccine closely matched circulating viruses and showed an excellent safety record," Chan said. "Emergency wards and intensive care units were often strained, few health systems were overwhelmed ... Schools closed, but borders remained open, and disruptions to travel and trade were far less severe than feared," she told delegates from the agency's 193 member states. "Had things gone wrong in any of these areas, we would have a very different agenda before us today," she added." US Researchers discover the mutation which had enabled the pandemic. WHO Director-General Margaret Chan officially declares the H1N1 pandemic over as countries are now seeing a mix of H1N1, H3N2, and B viruses, with some populaces displaying community-level immunity to H1N1 of 20% to 40%. Nevertheless, Angus Nicoll of the European Centre for Disease Prevention and Control urged health officials worldwide to "prepare for a new type of seasonal flu to appear in the near future that will combine elements of the pandemic A(H1N1) strain, and older A(H3N2) strain and several lesser strains". "Pandemics are unpredictable and prone to deliver surprises," Director-General Chan noted. US Researchers discover the mutation which had enabled the pandemic. WHO Director-General Margaret Chan officially declares the H1N1 pandemic over as countries are now seeing a mix of H1N1, H3N2, and B viruses, with some populaces displaying community-level immunity to H1N1 of 20% to 40%. Nevertheless, Angus Nicoll of the European Centre for Disease Prevention and Control urged health officials worldwide to "prepare for a new type of seasonal flu to appear in the near future that will combine elements of the pandemic A(H1N1) strain, and older A(H3N2) strain and several lesser strains". "Pandemics are unpredictable and prone to deliver surprises," Director-General Chan noted.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/List_of_epidemics_and_pandemics/html

List of epidemics and pandemics

This is a list of the largest known epidemics and pandemics caused by an infectious disease . Widespread non-communicable diseases such as cardiovascular disease and cancer are not included. An epidemic is the rapid spread of disease to a large number of people in a given population within a short period of time; in meningococcal infections , an attack rate in excess of 15 cases per 100,000 people for two consecutive weeks is considered an epidemic. Due to the long time spans, the first plague pandemic (6th century – 8th century) and the second plague pandemic (14th century – early 19th century) are shown by individual outbreaks, such as the Plague of Justinian (first pandemic) and the Black Death (second pandemic). Infectious diseases with high prevalence are listed separately (sometimes in addition to their epidemics), such as malaria , which may have killed 50–60 billion people throughout history, or about half of all humans that have ever lived. Ongoing epidemics and pandemics are in boldface . For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population . Not included in the above table are many waves of deadly diseases brought by Europeans to the Americas and Caribbean. Western Hemisphere populations were ravaged mostly by smallpox , but also typhus , measles , influenza , bubonic plague , cholera , malaria , tuberculosis , mumps , yellow fever , and pertussis . The lack of written records in many places and the destruction of many native societies by disease, war, and colonization make estimates uncertain. Deaths probably numbered in the tens or perhaps over a hundred million, with perhaps 90% of the population dead in the worst-hit areas. Lack of scientific knowledge about microorganisms and lack of surviving medical records for many areas makes attribution of specific numbers to specific diseases uncertain. There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll.Ongoing epidemics and pandemics are in boldface . For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population . Not included in the above table are many waves of deadly diseases brought by Europeans to the Americas and Caribbean. Western Hemisphere populations were ravaged mostly by smallpox , but also typhus , measles , influenza , bubonic plague , cholera , malaria , tuberculosis , mumps , yellow fever , and pertussis . The lack of written records in many places and the destruction of many native societies by disease, war, and colonization make estimates uncertain. Deaths probably numbered in the tens or perhaps over a hundred million, with perhaps 90% of the population dead in the worst-hit areas. Lack of scientific knowledge about microorganisms and lack of surviving medical records for many areas makes attribution of specific numbers to specific diseases uncertain.There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll.Events in boldface are ongoing.

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Oseltamivir/html

Oseltamivir

ethyl (3 R ,4 R ,5 S )-5-amino-4-acetamido-3-(pentan-3-yloxy)-cyclohex-1-ene-1-carboxylate CCC(CC)OC1C=C(CC(C1NC(=O)C)N)C(=O)OCC InChI=1S/C16H28N2O4/c1-5-12(6-2)22-14-9-11(16(20)21-7-3)8-13(17)15(14)18-10(4)19/h9,12-15H,5-8,17H2,1-4H3,(H,18,19)/t13-,14+,15+/m0/s1 Y Key:VSZGPKBBMSAYNT-RRFJBIMHSA-N Y Oseltamivir , sold under the brand name Tamiflu , is an antiviral medication used to treat and prevent influenza A and influenza B , viruses that cause the flu . Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid. Recommendations regarding oseltamivir are controversial as are criticisms of the recommendations. A 2014 Cochrane Review concluded that oseltamivir does not reduce hospitalizations, and that there is no evidence of reduction in complications of influenza. Two meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. They also found little evidence regarding whether treatment changes the risk of hospitalization or death in high risk populations. However, another meta-analysis found that oseltamivir was effective for prevention of influenza at the individual and household levels. Common side effects include vomiting , diarrhea , headache, and trouble sleeping. Other side effects may include psychiatric symptoms and seizures . In the United States it is recommended for influenza infection during pregnancy. It has been taken by a small number of pregnant women without signs of problems. Dose adjustment may be needed in those with kidney problems. Oseltamivir was approved for medical use in the US in 1999. It was the first neuraminidase inhibitor available by mouth. It is on the World Health Organization's List of Essential Medicines but was downgraded to "complementary" status in 2017. A generic version was approved in the US in 2016. In 2020, it was the 178th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Oseltamivir is used for the prevention and treatment of influenza caused by influenza A and B viruses. It is on the World Health Organization's List of Essential Medicines . The WHO supports its use for severe illness due to confirmed or suspected influenza virus infection in critically ill people who have been hospitalized. Oseltamivir's risk-benefit ratio is controversial. In 2017, it was moved from the core to the complementary list based on its lower cost-effectiveness. The Expert Committee did not recommend the deletion of oseltamivir from the EML and EMLc, recognizing that it is the only medicine included on the Model Lists for critically ill patients with influenza and for influenza pandemic preparedness. However, the Committee noted that, since the inclusion of oseltamivir on the Model List in 2009, new evidence in seasonal and pandemic influenza has lowered earlier estimates of the magnitude of effect of oseltamivir on relevant clinical outcomes. The Committee recommended that the listing of oseltamivir be amended, moving the medicine from the core to the Complementary List, and that its use be restricted to severe illness due to confirmed or suspected influenza virus infection in critically ill hospitalized patients. The Expert Committee noted that WHO guidelines for pharmacological management of pandemic and seasonal influenza would be updated in 2017: unless new information is provided to support the use of oseltamivir in seasonal and pandemic outbreaks, the next Expert Committee might consider oseltamivir for deletion. The US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), Public Health England and the American Academy of Pediatrics (AAP) recommend the use of oseltamivir for people who have complications or are at high risk for complications. This includes those who are hospitalized, young children, those over the age of 65, people with other significant health problems, those who are pregnant, and Indigenous peoples of the Americas among others. The Infectious Disease Society of America takes the same position as the CDC. A systematic review of systematic reviews in PLoS One did not find evidence for benefits in people who are at risk, noting that "the trials were not designed or powered to give results regarding serious complications, hospitalization and mortality", as did a 2014 Cochrane Review. The Cochrane Review further recommended: "On the basis of the findings of this review, clinicians and healthcare policy-makers should urgently revise current recommendations for use of the neuraminidase inhibitors (NIs) for individuals with influenza." That is not utilizing NIs for prevention or treatment "Based on these findings there appears to be no evidence for patients, clinicians or policy-makers to use these drugs to prevent serious outcomes, both in annual influenza and pandemic influenza outbreaks." The CDC, ECDC, Public Health England, Infectious Disease Society of America, the AAP, and Roche (the originator) reject the conclusions of the Cochrane Review, arguing in part that the analysis inappropriately forms conclusions about outcomes in people who are seriously ill based on results obtained primarily in healthy populations, and that the analysis inappropriately included results from people not infected with influenza. The EMA did not change its labeling of the drug in response to the Cochrane study. A 2014 review in the New England Journal of Medicine recommended that all people admitted to intensive care units during influenza outbreaks with a diagnosis of community-acquired pneumonia receive oseltamivir until the absence of influenza infection is established by PCR testing. A 2015 systematic review and meta-analysis found oseltamivir effective at treating the symptoms of influenza, reducing the length of hospitalization, and reducing the risk of otitis media . The same review found that oseltamivir did not significantly increase the risk of adverse events. A 2016 systematic review found that oseltamivir slightly reduced the time it takes for the symptoms of influenza to be alleviated, and that it also increased the risk of "nausea, vomiting, [and] psychiatric events in adults and vomiting in children." The decrease in duration of sickness was about 18 hours. In those who are otherwise healthy the CDC states that antivirals may be considered within the first 48 hours. A German clinical practice guideline recommends against its use. Two 2013 meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. When the analysis was restricted to people with confirmed infection, the same 2014 Cochrane Review (see above) found unclear evidence of change in the risk of complications such as pneumonia , while three other reviews found a decreased risk. Together, published studies suggest that oseltamivir reduces the duration of symptoms by 0.5–1.0 day. Any benefit of treatment must be balanced against side effects, which include psychiatric symptoms and increased rates of vomiting. The 2014 Cochrane Collaboration review concluded that oseltamivir did not affect the need for hospitalizations, and that there is no proof of reduction of complications of influenza (such as pneumonia) because of a lack of diagnostic definitions, or reduction of the spread of the virus. There was also evidence that suggested that oseltamivir prevented some people from producing sufficient numbers of their own antibodies to fight infection. The authors recommended that guidance should be revised to take account of the evidence of small benefit and increased risk of harms. The US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), the Public Health England (PHE), the Infectious Disease Society of America (IDSA), the American Academy of Pediatrics (AAP), and Roche (the originator) rejected the recommendations of the 2014 Cochrane Review to urgently change treatment guidelines and drug labels. As of 2017 [ update ] , the CDC does not recommend to use oseltamivir generally for prevention due to concerns that widespread use will encourage resistance development. They recommend that it be considered in those at high risk, who have been exposed to influenza within 48 hours and have not received or only recently been vaccinated. They recommended it during outbreaks in long term care facilities and in those who are significantly immunosuppressed. As of 2011 [ update ] , reviews concluded that when oseltamivir is used preventatively it decreases the risk of exposed people developing symptomatic disease. A systematic review of systematic reviews found low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1 to 12% (a relative decrease of 64 to 92%). It recommended against its use in healthy, low-risk persons due to cost, the risk of resistance development, and side effects and concluded it might be useful for prevention in unvaccinated high risk persons. The US Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), Public Health England and the American Academy of Pediatrics (AAP) recommend the use of oseltamivir for people who have complications or are at high risk for complications. This includes those who are hospitalized, young children, those over the age of 65, people with other significant health problems, those who are pregnant, and Indigenous peoples of the Americas among others. The Infectious Disease Society of America takes the same position as the CDC. A systematic review of systematic reviews in PLoS One did not find evidence for benefits in people who are at risk, noting that "the trials were not designed or powered to give results regarding serious complications, hospitalization and mortality", as did a 2014 Cochrane Review. The Cochrane Review further recommended: "On the basis of the findings of this review, clinicians and healthcare policy-makers should urgently revise current recommendations for use of the neuraminidase inhibitors (NIs) for individuals with influenza." That is not utilizing NIs for prevention or treatment "Based on these findings there appears to be no evidence for patients, clinicians or policy-makers to use these drugs to prevent serious outcomes, both in annual influenza and pandemic influenza outbreaks." The CDC, ECDC, Public Health England, Infectious Disease Society of America, the AAP, and Roche (the originator) reject the conclusions of the Cochrane Review, arguing in part that the analysis inappropriately forms conclusions about outcomes in people who are seriously ill based on results obtained primarily in healthy populations, and that the analysis inappropriately included results from people not infected with influenza. The EMA did not change its labeling of the drug in response to the Cochrane study. A 2014 review in the New England Journal of Medicine recommended that all people admitted to intensive care units during influenza outbreaks with a diagnosis of community-acquired pneumonia receive oseltamivir until the absence of influenza infection is established by PCR testing. A 2015 systematic review and meta-analysis found oseltamivir effective at treating the symptoms of influenza, reducing the length of hospitalization, and reducing the risk of otitis media . The same review found that oseltamivir did not significantly increase the risk of adverse events. A 2016 systematic review found that oseltamivir slightly reduced the time it takes for the symptoms of influenza to be alleviated, and that it also increased the risk of "nausea, vomiting, [and] psychiatric events in adults and vomiting in children." The decrease in duration of sickness was about 18 hours. In those who are otherwise healthy the CDC states that antivirals may be considered within the first 48 hours. A German clinical practice guideline recommends against its use. Two 2013 meta-analyses have concluded that benefits in those who are otherwise healthy do not outweigh its risks. When the analysis was restricted to people with confirmed infection, the same 2014 Cochrane Review (see above) found unclear evidence of change in the risk of complications such as pneumonia , while three other reviews found a decreased risk. Together, published studies suggest that oseltamivir reduces the duration of symptoms by 0.5–1.0 day. Any benefit of treatment must be balanced against side effects, which include psychiatric symptoms and increased rates of vomiting. The 2014 Cochrane Collaboration review concluded that oseltamivir did not affect the need for hospitalizations, and that there is no proof of reduction of complications of influenza (such as pneumonia) because of a lack of diagnostic definitions, or reduction of the spread of the virus. There was also evidence that suggested that oseltamivir prevented some people from producing sufficient numbers of their own antibodies to fight infection. The authors recommended that guidance should be revised to take account of the evidence of small benefit and increased risk of harms. The US Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), the Public Health England (PHE), the Infectious Disease Society of America (IDSA), the American Academy of Pediatrics (AAP), and Roche (the originator) rejected the recommendations of the 2014 Cochrane Review to urgently change treatment guidelines and drug labels. As of 2017 [ update ] , the CDC does not recommend to use oseltamivir generally for prevention due to concerns that widespread use will encourage resistance development. They recommend that it be considered in those at high risk, who have been exposed to influenza within 48 hours and have not received or only recently been vaccinated. They recommended it during outbreaks in long term care facilities and in those who are significantly immunosuppressed. As of 2011 [ update ] , reviews concluded that when oseltamivir is used preventatively it decreases the risk of exposed people developing symptomatic disease. A systematic review of systematic reviews found low to moderate evidence that it decreases the risk of getting symptomatic influenza by 1 to 12% (a relative decrease of 64 to 92%). It recommended against its use in healthy, low-risk persons due to cost, the risk of resistance development, and side effects and concluded it might be useful for prevention in unvaccinated high risk persons. Common adverse drug reactions (ADRs) associated with oseltamivir therapy (occurring in over 1 percent of people) include nausea and vomiting. In adults, oseltamivir increased the risk of nausea for which the number needed to harm was 28 and for vomiting was 22. So, for every 22 adult people on oseltamivir one experienced vomiting. In the treatment of children, oseltamivir also induced vomiting. The number needed to harm was 19. So, for every 19 children on oseltamivir one experienced vomiting. In prevention there were more headaches, kidney, and psychiatric events. Oseltamivir's effect on the heart is unclear: it may reduce cardiac symptoms, but may also induce serious arrhythmias. Postmarketing reports include liver inflammation and elevated liver enzymes, rash, allergic reactions including anaphylaxis , toxic epidermal necrolysis , abnormal heart rhythms , seizure, confusion, aggravation of diabetes, and haemorrhagic colitis and Stevens–Johnson syndrome . The US and EU package inserts for oseltamivir contain a warning of psychiatric effects observed in post-marketing surveillance. The frequency of these appears to be low and a causative role for oseltamivir has not been established. The 2014 Cochrane Review found a dose-response effect on psychiatric events. In trials of prevention in adults one person was harmed for every 94 treated. Neither of the two most cited published treatment trials of oseltamivir reported any drug-attributable serious adverse events. It is pregnancy category C in the United States and category B in Australia, meaning that it has been taken by a small number of women without signs of problems and in animal studies it looks safe. Dose adjustment may be needed in those with kidney problems. Oseltamivir is a neuraminidase inhibitor , a competitive inhibitor of influenza's neuraminidase enzyme. The enzyme cleaves the sialic acid which is found on glycoproteins on the surface of human cells that helps new virions to exit the cell, preventing new viral particles from being released. The vast majority of mutations conferring resistance are single amino acid residue substitutions (His274Tyr in N1) in the neuraminidase enzyme. A 2011 meta-analysis of 15 studies found a pooled incidence rate for oseltamivir resistance of 2.6%. Subgroup analyses detected higher rates among influenza A patients, especially the H1N1 subtype. It was found that a substantial number of patients might become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance might be significantly associated with pneumonia. In severely immunocompromised patients there were reports of prolonged shedding of oseltamivir- (or zanamivir )-resistant virus, even after oseltamivir treatment was stopped. As of December 15, 2010 [ update ] , the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide showed resistance to oseltamivir. The CDC found sporadic oseltamivir-resistant 2009 H1N1 virus infections had been identified, including with rare episodes of limited transmission, but the public health impact had been limited. Those sporadic cases of resistance were found in immunosuppressed patients during oseltamivir treatment and persons who developed illness while receiving oseltamivir chemoprophylaxis. During 2011, a new influenza A(H1N1)2009 variant with mildly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia. While there is concern that antiviral resistance may develop in people with haematologic malignancies due to their inability to reduce viral loads and several surveillance studies found oseltamivir-resistant pH1N1 after administration of oseltamivir in those people, as of November 2013 [ update ] , widespread transmission of oseltamivir-resistant pH1N1 has not occurred. During the 2007–08 flu season, the US CDC found 10.9% of H1N1 samples (n=1,020) to be resistant. In the 2008–09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2, B) showed resistance. From 2009 to 2014, oseltamivir resistance was very low in seasonal flu. In the 2010–11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remained oseltamivir susceptible in the US. In January 2012, the US and European CDCs reported all seasonal flu samples tested since October 2011 to be oseltamivir susceptible. In the 2013–14 season only 1% of 2009 H1N1 viruses showed oseltamivir resistance. No other influenza viruses were resistant to oseltamivir. Three studies have found resistance in 0%, 3.3%, and 18% of subjects. In the study with the 18% resistance rate, the subjects were children, many of whom had not been previously exposed to influenza virus and therefore had a weakened immune response; the results suggest that higher and earlier dosing may be necessary in such populations. In 2007, Japanese investigators detected neuraminidase-resistant influenza B virus strains in individuals not treated with these drugs. The prevalence was 1.7%. According to the CDC, As of 2019 [ update ] , transmission of oseltamivir-resistant influenza B virus strains—from persons treated with the drug—is rare. As of 2013 [ update ] , H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt. As of 2013 [ update ] , two of 14 adults infected with A(H7N9) and treated with oseltamivir developed oseltamivir-resistant virus with the Arg292Lys mutation. As of December 15, 2010 [ update ] , the World Health Organization (WHO) reported 314 samples of the prevalent 2009 pandemic H1N1 flu tested worldwide showed resistance to oseltamivir. The CDC found sporadic oseltamivir-resistant 2009 H1N1 virus infections had been identified, including with rare episodes of limited transmission, but the public health impact had been limited. Those sporadic cases of resistance were found in immunosuppressed patients during oseltamivir treatment and persons who developed illness while receiving oseltamivir chemoprophylaxis. During 2011, a new influenza A(H1N1)2009 variant with mildly reduced oseltamivir (and zanamivir) sensitivity was detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia. While there is concern that antiviral resistance may develop in people with haematologic malignancies due to their inability to reduce viral loads and several surveillance studies found oseltamivir-resistant pH1N1 after administration of oseltamivir in those people, as of November 2013 [ update ] , widespread transmission of oseltamivir-resistant pH1N1 has not occurred. During the 2007–08 flu season, the US CDC found 10.9% of H1N1 samples (n=1,020) to be resistant. In the 2008–09 season, the proportion of resistant H1N1 increased to 99.4%, while no other seasonal strains (H3N2, B) showed resistance. From 2009 to 2014, oseltamivir resistance was very low in seasonal flu. In the 2010–11 flu season, 99.1% of H1N1, 99.8% of H3N, and 100% of Influenza B remained oseltamivir susceptible in the US. In January 2012, the US and European CDCs reported all seasonal flu samples tested since October 2011 to be oseltamivir susceptible. In the 2013–14 season only 1% of 2009 H1N1 viruses showed oseltamivir resistance. No other influenza viruses were resistant to oseltamivir. Three studies have found resistance in 0%, 3.3%, and 18% of subjects. In the study with the 18% resistance rate, the subjects were children, many of whom had not been previously exposed to influenza virus and therefore had a weakened immune response; the results suggest that higher and earlier dosing may be necessary in such populations. In 2007, Japanese investigators detected neuraminidase-resistant influenza B virus strains in individuals not treated with these drugs. The prevalence was 1.7%. According to the CDC, As of 2019 [ update ] , transmission of oseltamivir-resistant influenza B virus strains—from persons treated with the drug—is rare. As of 2013 [ update ] , H274Y and N294S mutations that confer resistance to oseltamivir have been identified in a few H5N1 isolates from infected patients treated with oseltamivir, and have emerged spontaneously in Egypt. As of 2013 [ update ] , two of 14 adults infected with A(H7N9) and treated with oseltamivir developed oseltamivir-resistant virus with the Arg292Lys mutation. Its oral bioavailability is over 80% and is extensively metabolised to its active form upon first-pass through the liver. It has a volume of distribution of 23–26 litres. Its half-life is about 1–3 hours and its active carboxylate metabolite has a half-life of 6–10 hours. More than 90% of the oral dose is eliminated in the urine as the active metabolite. Oseltamivir was discovered by scientists at Gilead Sciences using shikimic acid as a starting point for synthesis ; shikimic acid was originally available only as an extract of Chinese star anise ; but by 2006, 30% of the supply was manufactured recombinantly in E. coli. Gilead exclusively licensed their relevant patents to Roche in 1996. The drug's patent has not been protected in Thailand, the Philippines, Indonesia, and several other countries. In 1999, the FDA approved oseltamivir phosphate for the treatment of influenza in adults based on two double-blind, randomized, placebo-controlled clinical trials. In June 2002, the European Medicines Agency (EMA) approved oseltamivir phosphate for prophylaxis and treatment of influenza. In 2003, a pooled analysis of ten randomised clinical trials concluded that oseltamivir reduced the risk of lower respiratory tract infections resulting in antibiotic use and hospital admissions in adults. Oseltamivir (as Tamiflu) was widely used during the H5N1 avian influenza epidemic in Southeast Asia in 2005. [ medical citation needed ] In response to the epidemic, various governments – including those of the United Kingdom, Canada, Israel, United States, and Australia – stockpiled quantities of oseltamivir in preparation for a possible pandemic and there were worldwide shortages of the drug, driven by the high demand for stockpiling. In November 2005, US President George W. Bush requested that Congress fund US$1 billion for the production and stockpile of oseltamivir, after Congress had already approved $1.8 billion for military use of the drug. Defense Secretary Donald Rumsfeld, who was a past chairman of Gilead Sciences, recused himself from all government decisions regarding the drug. In 2006, a Cochrane Review (since withdrawn) raised controversy by concluding that oseltamivir should not be used during routine seasonal influenza because of its low effectiveness. In December 2008, the Indian drug company Cipla won a case in India's court system allowing it to manufacture a cheaper generic version of Tamiflu, called Antiflu. In May 2009, Cipla won approval from the World Health Organization (WHO) certifying that its drug Antiflu was as effective as Tamiflu, and Antiflu is included in the WHO list of prequalified medicinal products. In 2009, a new A/H1N1 influenza virus was discovered to be spreading in North America. In June 2009, the WHO declared the A/H1N1 influenza a pandemic. The National Institute for Health and Care Excellence (NICE), the CDC, the WHO, and the ECDC maintained their recommendation to use oseltamivir. From 2010 to 2012, Cochrane requested Roche's full clinical study reports of their trials, which they did not provide. In 2011, a freedom of information request to the European Medicines Agency (EMA) provided Cochrane with reports from 16 Roche oseltamivir trials. In 2012, the Cochrane team published an interim review based on those reports. In 2013, Roche released 74 full clinical study reports of oseltamivir trials after GSK released the data on zanamivir studies. In 2014, Cochrane published an updated review based solely on full clinical study reports and regulatory documents. In 2016, Roche's oseltamivir patents began to expire. There have been [ when? ] reports of oseltamivir reducing disease severity and hospitalization time in canine parvovirus infection. The drug may limit the ability of the virus to invade the crypt cells of the small intestine and decrease gastrointestinal bacterial colonization and toxin production. Oseltamivir has been deemed ineffective at treating COVID-19 , consistent with the SARS-CoV-2 virus lacking influenza's neuraminidase enzyme.

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Pandemic influenza

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Orthomyxoviridae

Orthomyxoviridae (from Greek ὀρθός, orthós 'straight' + μύξα, mýxa ' mucus ') is a family of negative-sense RNA viruses . It includes seven genera : Alphainfluenzavirus , Betainfluenzavirus , Gammainfluenzavirus , Deltainfluenzavirus , Isavirus , Thogotovirus , and Quaranjavirus . The first four genera contain viruses that cause influenza in birds (see also avian influenza ) and mammals , including humans. Isaviruses infect salmon ; the thogotoviruses are arboviruses , infecting vertebrates and invertebrates (such as ticks and mosquitoes ). The Quaranjaviruses are also arboviruses , infecting vertebrates (birds) and invertebrates ( arthropods ). The four genera of Influenza virus that infect vertebrates, which are identified by antigenic differences in their nucleoprotein and matrix protein , are as follows:The influenzavirus virion is pleomorphic ; the viral envelope can occur in spherical and filamentous forms. In general, the virus's morphology is ellipsoidal with particles 100–120 nm in diameter, or filamentous with particles 80–100 nm in diameter and up to 20 µm long. There are approximately 500 distinct spike-like surface projections in the envelope each projecting 10–14 nm from the surface with varying surface densities. The major glycoprotein (HA) spike is interposed irregularly by clusters of neuraminidase (NA) spikes, with a ratio of HA to NA of about 10 to 1. The viral envelope composed of a lipid bilayer membrane in which the glycoprotein spikes are anchored encloses the nucleocapsids ; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The ribonuclear proteins are filamentous and fall in the range of 50–130 nm long and 9–15 nm in diameter with helical symmetry. [ citation needed ]Viruses of the family Orthomyxoviridae contain six to eight segments of linear negative-sense single stranded RNA. They have a total genome length that is 10,000–14,600 nucleotides (nt). The influenza A genome , for instance, has eight pieces of segmented negative-sense RNA (13.5 kilobases total). The best-characterised of the influenzavirus proteins are hemagglutinin and neuraminidase , two large glycoproteins found on the outside of the viral particles. Hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell. In contrast, neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. The hemagglutinin (H) and neuraminidase (N) proteins are key targets for antibodies and antiviral drugs, and they are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1 . The genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5′-end 12–13 nucleotides long. Nucleotide sequences of 3′-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3′-end 9–11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies. In Influenza A (H1N1) PB1-F2 is produced from an alternative reading frame in PB1. The M and NS genes produce two different genes via alternative splicing . Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings . Influenza can also be transmitted by saliva , nasal secretions , feces and blood . Infections occur through contact with these bodily fluids or with contaminated surfaces. Out of a host, flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F) , and indefinitely at very low temperatures (such as lakes in northeast Siberia ). They can be inactivated easily by disinfectants and detergents . The viruses bind to a cell through interactions between its hemagglutinin glycoprotein and sialic acid sugars on the surfaces of epithelial cells in the lung and throat (Stage 1 in infection figure). The cell imports the virus by endocytosis . In the acidic endosome , part of the hemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase into the cytoplasm (Stage 2). These proteins and vRNA form a complex that is transported into the cell nucleus , where the RNA-dependent RNA polymerase begins transcribing complementary positive-sense cRNA (Steps 3a and b). The cRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly synthesised viral proteins are either secreted through the Golgi apparatus onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs. Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell. After the release of new influenza virus, the host cell dies. Orthomyxoviridae viruses are one of two RNA viruses that replicate in the nucleus (the other being retroviridae ). This is because the machinery of orthomyxo viruses cannot make their own mRNAs. They use cellular RNAs as primers for initiating the viral mRNA synthesis in a process known as cap snatching . Once in the nucleus, the RNA Polymerase Protein PB2 finds a cellular pre-mRNA and binds to its 5′ capped end. Then RNA Polymerase PA cleaves off the cellular mRNA near the 5′ end and uses this capped fragment as a primer for transcribing the rest of the viral RNA genome in viral mRNA. This is due to the need of mRNA to have a 5′ cap in order to be recognized by the cell's ribosome for translation. Since RNA proofreading enzymes are absent, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly manufactured influenza virus will contain a mutation in its genome. The separation of the genome into eight separate segments of vRNA allows mixing ( reassortment ) of the genes if more than one variety of influenza virus has infected the same cell ( superinfection ). The resulting alteration in the genome segments packaged into viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an antigenic shift ). In a phylogenetic -based taxonomy , the category RNA virus includes the subcategory negative-sense ssRNA virus , which includes the order Articulavirales , and the family Orthomyxoviridae . The genera-associated species and serotypes of Orthomyxoviridae are shown in the following table.There are four genera of influenza virus, each containing only a single species, or type. Influenza A and C infect a variety of species (including humans), while influenza B almost exclusively infects humans, and influenza D infects cattle and pigs. Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N). 18 HA subtypes (or serotypes) and 11 NA subtypes of influenza A virus have been isolated in nature. Among these, the HA subtype 1-16 and NA subtype 1-9 are found in wild waterfowl and shorebirds and the HA subtypes 17-18 and NA subtypes 10-11 have only been isolated from bats. Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype. Examples of the nomenclature are: A/Brisbane/59/2007 (H1N1) A/Moscow/10/99 (H3N2). The type A influenza viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. It is thought that all influenza A viruses causing outbreaks or pandemics originate from wild aquatic birds. All influenza A virus pandemics since the 1900s were caused by Avian influenza , through Reassortment with human influenza strains (seasonal flu) or through adaptation in a mixing vessel (see 2009 swine flu pandemic ). The serotypes that have been confirmed in humans , ordered by the number of confirmed human deaths, are: Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal . This type of influenza mutates at a rate 2–3 times lower than type A and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift ), ensures that pandemics of influenza B do not occur. The influenza C virus infects humans and pigs , and can cause severe illness and local epidemics . However, influenza C is less common than the other types and usually causes mild disease in children. This is a genus that was classified in 2016, the members of which were first isolated in 2011. This genus appears to be most closely related to Influenza C, from which it diverged several hundred years ago. There are at least two extant strains of this genus. The main hosts appear to be cattle, but the virus has been known to infect pigs as well.Influenza A viruses are further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N). 18 HA subtypes (or serotypes) and 11 NA subtypes of influenza A virus have been isolated in nature. Among these, the HA subtype 1-16 and NA subtype 1-9 are found in wild waterfowl and shorebirds and the HA subtypes 17-18 and NA subtypes 10-11 have only been isolated from bats. Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype. Examples of the nomenclature are: A/Brisbane/59/2007 (H1N1) A/Moscow/10/99 (H3N2). The type A influenza viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. It is thought that all influenza A viruses causing outbreaks or pandemics originate from wild aquatic birds. All influenza A virus pandemics since the 1900s were caused by Avian influenza , through Reassortment with human influenza strains (seasonal flu) or through adaptation in a mixing vessel (see 2009 swine flu pandemic ). The serotypes that have been confirmed in humans , ordered by the number of confirmed human deaths, are:Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal . This type of influenza mutates at a rate 2–3 times lower than type A and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift ), ensures that pandemics of influenza B do not occur. The influenza C virus infects humans and pigs , and can cause severe illness and local epidemics . However, influenza C is less common than the other types and usually causes mild disease in children. This is a genus that was classified in 2016, the members of which were first isolated in 2011. This genus appears to be most closely related to Influenza C, from which it diverged several hundred years ago. There are at least two extant strains of this genus. The main hosts appear to be cattle, but the virus has been known to infect pigs as well.Mammalian influenza viruses tend to be labile, but can survive several hours in mucus. Avian influenza virus can survive for 100 days in distilled water at room temperature, and 200 days at 17 °C (63 °F) . The avian virus is inactivated more quickly in manure, but can survive for up to two weeks in feces on cages. Avian influenza viruses can survive indefinitely when frozen. Influenza viruses are susceptible to bleach, 70% ethanol, aldehydes, oxidizing agents, and quaternary ammonium compounds. They are inactivated by heat of 133 °F (56 °C) for minimum of 60 minutes, as well as by low pH <2. Vaccines and drugs are available for the prophylaxis and treatment of influenza virus infections. Vaccines are composed of either inactivated or live attenuated virions of the H1N1 and H3N2 human influenza A viruses, as well as those of influenza B viruses. Because the antigenicities of the wild viruses evolve, vaccines are reformulated annually by updating the seed strains. [ citation needed ] When the antigenicities of the seed strains and wild viruses do not match, vaccines fail to protect the vaccinees. [ citation needed ] In addition, even when they do match, escape mutants are often generated. [ citation needed ] Drugs available for the treatment of influenza include Amantadine and Rimantadine , which inhibit the uncoating of virions by interfering with M2, and Oseltamivir (marketed under the brand name Tamiflu ), Zanamivir , and Peramivir , which inhibit the release of virions from infected cells by interfering with NA. However, escape mutants are often generated for the former drug and less frequently for the latter drug.

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Pandemic influenza

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Influenza Genome Sequencing Project

The Influenza Genome Sequencing Project ( IGSP ), initiated in early 2004, seeks to investigate influenza evolution by providing a public data set of complete influenza genome sequences from collections of isolates representing diverse species distributions. The project is funded by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), and has been operating out of the NIAID Microbial Sequencing Center at The Institute for Genomic Research (TIGR, which in 2006 became The Venter Institute). Sequence information generated by the project has been continually placed into the public domain through GenBank .In late 2003, David Lipman , Lone Simonsen , Steven Salzberg , and a consortium of other scientists wrote a proposal to begin sequencing large numbers of influenza viruses at The Institute for Genomic Research (TIGR). Prior to this project, only a handful of flu genomes were publicly available. [ citation needed ] Their proposal was approved by the National Institutes of Health (NIH), and would later become the IGSP. New technology development led by Elodie Ghedin began at TIGR later that year, and the first publication describing > 100 influenza genomes appeared in 2005 in the journal Nature The project makes all sequence data publicly available through GenBank , an international, NIH-funded, searchable online database. This research helps to provide international researchers with the information needed to develop new vaccines , therapies and diagnostics, as well as improve understanding of the overall molecular evolution of Influenza and other genetic factors that determine their virulence. [ citation needed ] Such knowledge could not only help mitigate the impact of annual influenza epidemics , but could also improve scientific knowledge of the emergence of pandemic influenza viruses .The project completed its first genomes in March 2005 and has rapidly accelerated since. By mid-2008, over 3000 isolates had been completely sequenced from influenza viruses that are endemic in human ("human flu") avian ("bird flu") and swine ("swine flu") populations, including many strains of H3N2 (human), H1N1 (human), and H5N1 (avian). The project is funded by the National Institute of Allergy and Infectious Diseases (NIAID) which is a component of the NIH, which is an agency of the United States Department of Health and Human Services . The IGSP has expanded to include a growing list of collaborators, who have contributed both expertise and valuable collections of influenza isolates. Key early contributors included Peter Palese of the Mount Sinai School of Medicine in New York, Jill Taylor of the Wadsworth Center at the New York State Department of Health , Lance Jennings of Canterbury Health Laboratories (New Zealand), Jeff Taubenberger of the Armed Forces Institute of Pathology (who later moved to NIH), Richard Slemons of Ohio State University and Rob Webster of St. Jude's Children's Hospital in Memphis, Tennessee. In 2006 the project was joined by Ilaria Capua of the Istituto Zooprofilattico Sperimentale delle Venezie (in Italy), who contributed a valuable collection of avian flu isolates (including multiple H5N1 strains). Some of these avian isolates were described in a publication in Emerging Infectious Diseases in 2007. Nancy Cox from the Centers for Disease Control and Prevention (CDC) and Robert Couch from Baylor College of Medicine also joined the project in 2006, contributing over 150 influenza B isolates. The project began prospective studies of the 2007 influenza season with collaborators Florence Bourgeois and Kenneth Mandl of Children's Hospital Boston and the Harvard School of Public Health and Laurel Edelman of Surveillance Data Inc. [ citation needed ]

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Pandemic influenza

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2009 swine flu pandemic in the United States

The 2009 flu pandemic in the United States was caused by a novel strain of the Influenza A/H1N1 virus, commonly referred to as " swine flu ", that was first detected on 15 April 2009. While the 2009 H1N1 virus strain was commonly referred to as "swine flu", there is no evidence that it is endemic to pigs (i.e. actually a swine flu) or of transmission from pigs to people; instead, the virus spreads from person to person. On April 25, the World Health Organization declared a public health emergency, followed concurringly by the Obama administration on April 26. The U.S. Centers for Disease Control and Prevention (CDC) reported that during the outbreak about half of all influenza viruses being reported were 2009 H1N1 viruses, with the other half being those of the regular seasonal influenza. Unique to this particular strain, about 60% of the 2009 H1N1 influenza cases were occurring among people between 5 years and 24 years of age, and 40% of the hospitalizations were occurring among children and young adults. About 80% of the deaths were in people younger than 65 years of age. The CDC noted that this differed greatly from typical seasonal influenza epidemics, during which about 70% to 90% of deaths are estimated to occur in people 65 years and older. Antibody studies showed that children had no existing cross-reactive antibody to the 2009 H1N1 influenza virus, while about one-third of adults older than 60 years of age had cross-reactive antibody. By April 21, 2009, CDC had begun working to develop a virus that could be used to make a vaccine to protect against the new virus. Following preparation for distribution beginning in June, the first doses were administered in October 2009. On August 10, 2010, WHO declared an end to the global 2009 H1N1 influenza pandemic. However, the virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year. From April 12, 2009, to April 10, 2010, the CDC estimates there were 60.8 million cases (range: 43.3 - 89.3 million), 274,304 hospitalizations (range: 195,086 - 402,719), and 12,469 deaths (range: 8868 - 18,306) in the United States due to the virus. A follow-up study done in September 2010 showed that the risk of serious illness resulting from the 2009 H1N1 flu was no higher than that of the yearly seasonal flu . For comparison, the CDC estimates the global H1N1 death toll at 284,000 and the WHO estimates that 250,000 to 500,000 people die of seasonal flu annually. The earliest reported cases in the US began appearing in early April 2009, in California. In late April, the Centers for Disease Control and Prevention (CDC) activated its Emergency Operations Center and declared a public health emergency. On April 25, the World Health Organization (WHO) declared a public health emergency of international concern. WHO declared H1N1 a pandemic on June 11. [ citation needed ] By the end of May, the flu had infected people in all 50 states. As of June 16, the total number of confirmed cases was 27,717 and on June 25, the CDC said there were over one million (1,000,000) cases, most of which had not been reported or diagnosed. Deaths relating to influenza began appearing in the US in late April, and by early June, 15 states had reported fatalities related to or directly occurring from the virus. By October 5, the first doses of an H1N1 vaccine were given in the U.S. The CDC distributed vaccines for the flu using mechanisms already in place for its Vaccines for Children (VFC) program. On October 24, and the CDC said more than 1,000 had died from the flu. President Obama declared a national emergency. On December 10, 2009, the CDC reported an estimated 50 million Americans or 1 in 6 had been infected and 10,000 had died. On December 23, 2009, the CDC reported a reduction of the disease by 59% percent. On February 12, the CDC reported 57 million Americans had been sickened, 257,000 had been hospitalized and 11,690 people had died (including 1,180 children) due to flu from April through to mid-January. The Centers for Disease Control and Prevention (CDC) identified the first two A/09(H1N1) swine flu cases in California on April 17, 2009, via the Border Infectious Disease Program, for a San Diego County child, and a naval research facility studying a special diagnostic test, where influenza sample from the child from Imperial County was tested. By April 21, enhanced surveillance was established to search for additional cases in both California and Texas and the CDC determined that the virus strain was genetically similar to the previously known A(H1N1) swine flu circulating among pigs in the United States since about 1999. [ citation needed ] It was established that the virus was a combination of human, North American swine, and Eurasian swine influenza viruses; the viruses from the initial two Californian cases were also noted to be resistant to amantadine and rimantadine , two common influenza antiviral drugs. No contact with pigs was found for any of the seven Californian nor either of the two Texas cases, suggesting human-to-human transmission of the virus. [ citation needed ] On April 28, 2009, the director of the Centers for Disease Control and Prevention confirmed the first official US death of swine flu. Tests confirmed that a 23-month-old toddler from Mexico, who was probably infected there, died on April 27 from the flu while visiting Texas. Cases of H1N1 spread rapidly across the United States, with particularly severe outbreaks in Texas, New York, Utah, and California. Early cases were associated with recent travel to Mexico; many were students who had traveled to Mexico for spring break. On May 4, 2009, the CDC reported one death, 286 confirmed cases of H1N1 flu across 36 states, 35 hospitalizations, and expected H1N1 to eventually spread to all states. A large number of cases, according to medics, have happened in the days that preceded the launch of the alert and came out only in these days due to a massive backlog. By May 5, 2009, the number had risen to 403 and a second death was reported in Texas. The CDC and government officials had expressed cautious optimism about the severity and spread of H1N1. Changes in surveillance of cases of influenza-like illness , including new guidelines for identifying cases to test, increased laboratory testing, and new test kits able to distinguish this novel strain, resulted in a spike in the percent of cases tested positive for influenza. Of the positive cases, about a third were due to the novel strain. Also found were a substantial number of cases where the strain could not be subtyped. The proportion of US deaths due to pneumonia and influenza climbed above the epidemic threshold in the 2007–2008 winter flu season but not in the 2008–2009 season. Although the 2009 H1N1 outbreak reached epidemic levels of infection early in 2009, it did not contribute to epidemic levels of pneumonia and influenza related deaths until October 2009. [ citation needed ] In early October 2009, the Centers for Disease Control and Prevention announced that swine flu was widespread across the country. It also said there was significant flu activity in virtually all states, which was considered to be quite unusual for this time of year. There was particular worry about pregnant women. As of late August, 100 had been hospitalized in intensive care units and 28 had died since the beginning of the outbreak in April. On October 1, it was acknowledged that a recruit in basic training in Fort Jackson, South Carolina, was the Army's first swine flu death. The recruit fell ill on September 1 and died of pneumonia on September 10. [ citation needed ] Dell Children's Medical Center in Austin, Texas, erected two tents in its parking lot to handle emergency room visits, and hospitals around Colorado Springs recorded a 30 percent spike in flu visits. As pediatric cases were increasing, the Dept. of Health and Human Services released 300,000 courses of children's liquid Tamiflu from the national pandemic stockpile in late September, with the first batches sent to Texas and Colorado. [ citation needed ] In late September, the disease centers reported that 936 had died of flu symptoms or of flu-associated pneumonia since August 30, when it began a new count of deaths, including some without laboratory-confirmed swine flu. The Agriculture Department reported on October 16 that three pigs at the Minnesota State Fair, in St. Paul, were tested positive in late August for H1N1 virus, which were the first cases in the country, although infected pigs had been found in eight other countries. There were 103 pigs tested at the Fair, including the three infected, though all appeared healthy. Scientists said the virus was already spreading widely among people, and, in fact, was more common in humans than in pigs, so humans were more likely to catch it from others than from pigs. In mid-October, it was reported that flu caused by the H1N1 virus was widespread in 41 states, and flu-like illnesses accounted for 6.1 percent of all doctor visits, which was considered high [ citation needed ] , particularly for October. Forty-three children had died from H1N1 since August 30, which is approximately the number that usually dies in an entire flu season. Nineteen of the forty-three were teenagers while sixteen were between ages five to eleven. The rest were under five. [ citation needed ] It is reported that the severity of the disease was not increasing. About fifteen to twenty percent of the patients hospitalized for the flu were placed in the intensive care unit, a level similar to that for seasonal flu. [ citation needed ] Projections of the supply of H1N1 vaccine had decreased significantly from a level of 120 million doses ready in October, estimated during the summer, to an estimate of 28 to 30 million doses by the end of the month. On October 14, 11.4 million doses of the H1N1 vaccine were said to be available. As of November 20, 2009, the CDC reported sharp declines in H1N1 activity throughout the United States, with influenza-like illness (which may also include meningitis, pneumonia, strep pharyngitis, gastroenteritis, and the common cold) accounting for 5.5% of doctors visits, down sharply from 8% in late October, the peak of the second wave. However, taking the vaccine is still urged by the CDC, as a third wave of the disease may sweep across the US, possibly in January/February 2010. [ needs update ] As of December 24, the second wave of H1N1 has clearly peaked, with pneumonia and influenza deaths falling below the epidemic threshold for the first time in 11 weeks, and the proportion of doctors visits due to influenza-like illness falling to baseline (2.3%), down from 5.5% 1 month before, on November 20. However, it was reported that influenza activity was beginning to increase in West Virginia, with 5.2% of patients treated by West Virginia health care providers having influenza-like illness, a major increase from 2% of patients treated by West Virginia health care providers having influenza-like illness in November. [ citation needed ] On August 10, 2010, WHO declared an end to the global 2009 H1N1 influenza pandemic. However, the virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year. In early October 2009, the Centers for Disease Control and Prevention announced that swine flu was widespread across the country. It also said there was significant flu activity in virtually all states, which was considered to be quite unusual for this time of year. There was particular worry about pregnant women. As of late August, 100 had been hospitalized in intensive care units and 28 had died since the beginning of the outbreak in April. On October 1, it was acknowledged that a recruit in basic training in Fort Jackson, South Carolina, was the Army's first swine flu death. The recruit fell ill on September 1 and died of pneumonia on September 10. [ citation needed ] Dell Children's Medical Center in Austin, Texas, erected two tents in its parking lot to handle emergency room visits, and hospitals around Colorado Springs recorded a 30 percent spike in flu visits. As pediatric cases were increasing, the Dept. of Health and Human Services released 300,000 courses of children's liquid Tamiflu from the national pandemic stockpile in late September, with the first batches sent to Texas and Colorado. [ citation needed ] In late September, the disease centers reported that 936 had died of flu symptoms or of flu-associated pneumonia since August 30, when it began a new count of deaths, including some without laboratory-confirmed swine flu. The Agriculture Department reported on October 16 that three pigs at the Minnesota State Fair, in St. Paul, were tested positive in late August for H1N1 virus, which were the first cases in the country, although infected pigs had been found in eight other countries. There were 103 pigs tested at the Fair, including the three infected, though all appeared healthy. Scientists said the virus was already spreading widely among people, and, in fact, was more common in humans than in pigs, so humans were more likely to catch it from others than from pigs. In mid-October, it was reported that flu caused by the H1N1 virus was widespread in 41 states, and flu-like illnesses accounted for 6.1 percent of all doctor visits, which was considered high [ citation needed ] , particularly for October. Forty-three children had died from H1N1 since August 30, which is approximately the number that usually dies in an entire flu season. Nineteen of the forty-three were teenagers while sixteen were between ages five to eleven. The rest were under five. [ citation needed ] It is reported that the severity of the disease was not increasing. About fifteen to twenty percent of the patients hospitalized for the flu were placed in the intensive care unit, a level similar to that for seasonal flu. [ citation needed ] Projections of the supply of H1N1 vaccine had decreased significantly from a level of 120 million doses ready in October, estimated during the summer, to an estimate of 28 to 30 million doses by the end of the month. On October 14, 11.4 million doses of the H1N1 vaccine were said to be available. As of November 20, 2009, the CDC reported sharp declines in H1N1 activity throughout the United States, with influenza-like illness (which may also include meningitis, pneumonia, strep pharyngitis, gastroenteritis, and the common cold) accounting for 5.5% of doctors visits, down sharply from 8% in late October, the peak of the second wave. However, taking the vaccine is still urged by the CDC, as a third wave of the disease may sweep across the US, possibly in January/February 2010. [ needs update ] As of December 24, the second wave of H1N1 has clearly peaked, with pneumonia and influenza deaths falling below the epidemic threshold for the first time in 11 weeks, and the proportion of doctors visits due to influenza-like illness falling to baseline (2.3%), down from 5.5% 1 month before, on November 20. However, it was reported that influenza activity was beginning to increase in West Virginia, with 5.2% of patients treated by West Virginia health care providers having influenza-like illness, a major increase from 2% of patients treated by West Virginia health care providers having influenza-like illness in November. [ citation needed ] On August 10, 2010, WHO declared an end to the global 2009 H1N1 influenza pandemic. However, the virus continues to circulate as a seasonal flu virus, and cause illness, hospitalization, and deaths worldwide every year. The new strain was identified as a combination of several different strains of Influenzavirus A , subtype H1N1 , including separate strains of this subtype circulating in humans (see human influenza ) and in pigs (see swine influenza ). The strain transmits between humans and was initially reported to have a relatively high mortality rate in Mexico. In April 2009 the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) expressed serious concerns that the new strain had the potential to become an influenza pandemic . On April 25 it was reported that, because the virus was already widespread, containment would be "nearly impossible." By this time, there had also been speculation that the flu death toll in Mexico could be lower than first thought. Gerald Evans, head of the Association of Medical Microbiology and Infectious Disease Canada and a member of a federal pandemic-planning committee, said on April 29: There was a lot of speculation and what seemed to be evidence there were dozens and dozens of deaths. Careful analysis showed these people likely died of something else, and not influenza. That's really good news, and that would fit with what we've seen outside of Mexico. Another Canadian expert, Neil Rau, criticized the WHO's decision to raise its pandemic alert to level 5, saying: I don't agree with (the WHO) because I think it's a panic metre, not a pandemic metre. [...] If that flu-like illness is not deadly, I don't know what the cause for alarm is for people who are not really sickened by this virus. [...] I'm really eager to know how much worse this is than seasonal flu. So far it's looking like it's not that serious. CNN noted on April 28, 2009, that in any individual week between January 1 and April 18, there had been at least 800 deaths in the U.S. due to normal influenza, which is higher than the 150 total deaths worldwide from the swine flu up to that time. As of May 28, 2010, the official U.S. death toll attributed directly to the novel H1N1 and seasonal influenza was 2,117. This total exceeds the 849 U.S. deaths directly attributed to seasonal influenza in 2006. Many of the other deaths commonly attributed to influenza are caused by complicated influenza, where a second infection causes death, usually pneumonia (of which 48,657 of 55,477 official deaths in 2006 occurred in people aged 65 years and older). The final estimate was of over 12,000 deaths over the course of the pandemic (April 2009 – April 2010). The CDC reported that during the outbreak about half of all influenza viruses being detected through laboratory reports were 2009 H1N1 viruses, with the other half being those of the regular seasonal influenza viruses. Surveillance reports indicated that about 57% of the 2009 H1N1 influenza confirmed and probable cases were occurring among people between 5 years and 24 years of age, and 41% of the hospitalizations were occurring among older children and young adults. The highest rates of hospitalization were among children younger than 5 years of age; the next highest hospitalization rate was in people 5 years to 24 years of age. Antibody studies showed that children had no existing cross-reactive antibody to the 2009 H1N1 influenza virus, while about one-third of adults older than 60 years of age had cross-reactive antibody. One possible explanation for this pre-existing antibody in older adults was that they may have had previous exposure, either through infection or vaccination, to an influenza A H1N1 virus that was more closely related to the 2009 H1N1 flu virus. Based on data from previous influenza pandemics and seasonal influenza, pregnant women had been recognized as a high-risk group early in the outbreak. People with other previously recognized medical conditions that placed them at high risk of complications from seasonal influenza also appeared to be at increased risk of complications from 2009 H1N1 influenza. One report found that seventy-one percent of hospitalized patients had one or more underlying chronic medical conditions and reported deaths had occurred in people ranging in age from 22 months old to 57 years old. Also, only 13% of hospitalizations had occurred in people 50 years and older, and there were few cases and no deaths in people older than 65 years, which was unusual when compared with seasonal flu. The CDC reported that during the outbreak about half of all influenza viruses being detected through laboratory reports were 2009 H1N1 viruses, with the other half being those of the regular seasonal influenza viruses. Surveillance reports indicated that about 57% of the 2009 H1N1 influenza confirmed and probable cases were occurring among people between 5 years and 24 years of age, and 41% of the hospitalizations were occurring among older children and young adults. The highest rates of hospitalization were among children younger than 5 years of age; the next highest hospitalization rate was in people 5 years to 24 years of age. Antibody studies showed that children had no existing cross-reactive antibody to the 2009 H1N1 influenza virus, while about one-third of adults older than 60 years of age had cross-reactive antibody. One possible explanation for this pre-existing antibody in older adults was that they may have had previous exposure, either through infection or vaccination, to an influenza A H1N1 virus that was more closely related to the 2009 H1N1 flu virus. Based on data from previous influenza pandemics and seasonal influenza, pregnant women had been recognized as a high-risk group early in the outbreak. People with other previously recognized medical conditions that placed them at high risk of complications from seasonal influenza also appeared to be at increased risk of complications from 2009 H1N1 influenza. One report found that seventy-one percent of hospitalized patients had one or more underlying chronic medical conditions and reported deaths had occurred in people ranging in age from 22 months old to 57 years old. Also, only 13% of hospitalizations had occurred in people 50 years and older, and there were few cases and no deaths in people older than 65 years, which was unusual when compared with seasonal flu. The Federal response remained at US Pandemic Stage 0, congruent with the World Health Organization (WHO) Pandemic Phases 1, 2 and 3; however, the WHO's Pandemic Phase was raised to 4 on April 27, which is congruent with US Pandemic Stage 2. On April 29, the WHO raised the pandemic alert level to phase 5. The United States federal government declared a public health emergency , and several U.S. states then indicated that they may follow suit. Secretary of Homeland Security Janet Napolitano noted that this declaration was standard operating procedure, which was also done for the 2009 presidential inauguration and for flooding. After many days of deliberation the WHO declared that the current influenza had become a true pandemic, raising the Pandemic Alert level to Phase 6, the highest on the WHO scale and congruent with U.S. Federal Government Response Stages 3–6. An official for the White House said on April 24 that "the White House is taking the situation seriously and monitoring for any new developments. The president has been fully briefed." President Barack Obama stated that "We are closely monitoring the emerging cases of swine flu." He also noted, "This is obviously a cause for concern ... but it is not a cause for alarm." Obama suggested that U.S. schools should consider shutting down, as a future possibility, if their students were to become infected. White House Press Secretary Robert Gibbs said the effort to get a team in place to respond to the health scare had not been hindered by the lack of a secretary of Health and Human Services or appointees in any of the department's 19 key posts. The president's nominee, Kansas Gov. Kathleen Sebelius , was still awaiting confirmation from the U.S. Senate until passing on April 28. The President had not yet made appointments to either the Commissioner of the Food and Drug Administration , the Surgeon General , or the Director of the Centers for Disease Control and Prevention . The current acting Surgeon General, Steven K. Galson , was also currently serving as the Acting Assistant Secretary for Health. On April 30, it was reported that an aide to Steven Chu , the US Energy Secretary, had fallen ill from the virus after helping arrange President Obama's trip to Mexico. However, the White House stated that the President was not at risk of contracting the flu. Kathleen Sebelius was confirmed as the Secretary of Health and Human Services by the Senate on April 28, 2009, with a vote of 65–31. On October 24, President Obama declared the 2009 H1N1 swine flu a national emergency. The declaration made it easier for U.S. medical facilities to handle a surge in flu patients by allowing the waiver of some requirements of Medicare , Medicaid and other federal health insurance programs as needed. During the week of April 19, 2009, the CDC activated its Emergency Operations Center (EOC), with RADM Stephen Redd as the Incident Commander, to augment the ongoing investigation of human cases of swine influenza A (H1N1). More than 250 CDC professionals worked from the CDC EOC as part of the agency's response. As of May 4, 2009, the CDC reported that it had deployed 25% of the supplies and medicines in the Strategic National Stockpile to the various states. As of April 29, only the CDC could confirm U.S. swine flu cases. Besser stated during an April 30 press briefing that California and New York had diagnostic test kits, and that the kits would be sent to all states starting the following day. On May 6, the CDC announced that testing kits were now available for all states. It was expected this would generate an increase in the number of confirmed cases as more states began doing their own tests. In the United States, the majority of the 70 National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories do not report the influenza A subtype. [ citation needed ] However, in 2007, human infection with a novel influenzavirus A became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that are unsubtypable with standard methods and reagents. The new strain responsible for this outbreak was one such virus. [ citation needed ] Initially the CDC had issued a recommendation that schools close for as long as two weeks if a student catches swine flu. Some school districts closed all schools if a single child was classified as probable. On May 5 the CDC retracted its advice stating that schools that were closed based on previous CDC guidance related to this outbreak may reopen. By that time at least 726 schools nationwide serving more than 480,000 students had closed for at least some period of time. The CDC amended its advice, citing new information on disease severity and the limiting effectiveness of school closure as a control measure. The new advice given stated, "Decisions about school closure should be at the discretion of local authorities based on local considerations, including public concern and the impact of school absenteeism and staffing shortages." The Food and Drug Administration (FDA) authorized emergency use of medicines and diagnostic tests for flu. (FDA is part of Department of Health and Human Services.) The FDA stated it was also responding to this threat by: working with other government agencies and manufacturers on a series of issues related to antiviral medications. growing the 2009 H1N1 flu virus and preparing to make vaccine seed lots, which may be used eventually to produce a safe and effective vaccine. helping to prepare reagents needed for vaccine production and coordinating closely with other public health agencies for clinical development and testing. accelerating access to new diagnostic tools for this 2009 H1N1 flu virus On May 6, 2009, the FDA announced that it had approved a new manufacturing facility for seasonal flu vaccine, owned by Sanofi Pasteur, which could also be used for manufacturing a vaccine for the new H1N1 flu strain. The FDA also issued a warning for consumers to be wary of products claiming to cure or prevent swine flu. Secretary Napolitano stated that DHS was the principal federal office for incidents such as the H1N1 flu outbreak, and "Under that role, we have been leading a true collaborative effort." The Department of Homeland Security issued a document, dated November 1, 2005, entitled "National Strategy for Pandemic Influenza", detailing planning for potential pandemics. https://web.archive.org/web/20090507013213/http://www.pandemicflu.gov/plan/federal/pandemic-influenza.pdf The State Department suggested travelers to Mexico stay alert and comply with guidance from Mexican public health officials, but did not impose any travel restrictions on US citizens to Mexico. However, the State Department did recommend US citizens avoid non-essential travel to Mexico. The Department of Agriculture (USDA) reported no swine in the US have been infected so far, but the USDA is monitoring swine across the US for signs of infection. The Department of Commerce sent a letter to Russia and China requesting that those countries lift their ban on American pork products. The Department of Defense (DOD) monitored the swine flu situation and had contingency plans to deal with such outbreaks. As of May 7, 2009, the DOD reported 104 confirmed cases among Armed Forces personnel and their families. DOD maintained a daily summary and map. The Department of Education provided guidance to schools in the US affected by swine flu, as well as precautions to take. Schools closed in many states in response to local flu outbreaks. By April 30, 2009, 300 U.S. schools and school districts had announced closures in response to the outbreak, giving 169,000 students time off. On May 4, 2009, about 533 schools in 24 states in the U.S. were closed, affecting about 330,000 students. On September 25, 2009, 42 schools were closed in eight states as the second wave of the pandemic began. On May 5, Kathleen Sebelius stated in a CDC news conference that school closures for single confirmed cases of H1N1 influenza were unnecessary, but that children displaying an influenza-like illness should stay home. Several US airlines waived fees for cancellations and flight changes. At least one cruise line changed itinerary to avoid Mexican ports of call. An official for the White House said on April 24 that "the White House is taking the situation seriously and monitoring for any new developments. The president has been fully briefed." President Barack Obama stated that "We are closely monitoring the emerging cases of swine flu." He also noted, "This is obviously a cause for concern ... but it is not a cause for alarm." Obama suggested that U.S. schools should consider shutting down, as a future possibility, if their students were to become infected. White House Press Secretary Robert Gibbs said the effort to get a team in place to respond to the health scare had not been hindered by the lack of a secretary of Health and Human Services or appointees in any of the department's 19 key posts. The president's nominee, Kansas Gov. Kathleen Sebelius , was still awaiting confirmation from the U.S. Senate until passing on April 28. The President had not yet made appointments to either the Commissioner of the Food and Drug Administration , the Surgeon General , or the Director of the Centers for Disease Control and Prevention . The current acting Surgeon General, Steven K. Galson , was also currently serving as the Acting Assistant Secretary for Health. On April 30, it was reported that an aide to Steven Chu , the US Energy Secretary, had fallen ill from the virus after helping arrange President Obama's trip to Mexico. However, the White House stated that the President was not at risk of contracting the flu. Kathleen Sebelius was confirmed as the Secretary of Health and Human Services by the Senate on April 28, 2009, with a vote of 65–31. On October 24, President Obama declared the 2009 H1N1 swine flu a national emergency. The declaration made it easier for U.S. medical facilities to handle a surge in flu patients by allowing the waiver of some requirements of Medicare , Medicaid and other federal health insurance programs as needed.During the week of April 19, 2009, the CDC activated its Emergency Operations Center (EOC), with RADM Stephen Redd as the Incident Commander, to augment the ongoing investigation of human cases of swine influenza A (H1N1). More than 250 CDC professionals worked from the CDC EOC as part of the agency's response. As of May 4, 2009, the CDC reported that it had deployed 25% of the supplies and medicines in the Strategic National Stockpile to the various states. As of April 29, only the CDC could confirm U.S. swine flu cases. Besser stated during an April 30 press briefing that California and New York had diagnostic test kits, and that the kits would be sent to all states starting the following day. On May 6, the CDC announced that testing kits were now available for all states. It was expected this would generate an increase in the number of confirmed cases as more states began doing their own tests. In the United States, the majority of the 70 National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories do not report the influenza A subtype. [ citation needed ] However, in 2007, human infection with a novel influenzavirus A became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that are unsubtypable with standard methods and reagents. The new strain responsible for this outbreak was one such virus. [ citation needed ] Initially the CDC had issued a recommendation that schools close for as long as two weeks if a student catches swine flu. Some school districts closed all schools if a single child was classified as probable. On May 5 the CDC retracted its advice stating that schools that were closed based on previous CDC guidance related to this outbreak may reopen. By that time at least 726 schools nationwide serving more than 480,000 students had closed for at least some period of time. The CDC amended its advice, citing new information on disease severity and the limiting effectiveness of school closure as a control measure. The new advice given stated, "Decisions about school closure should be at the discretion of local authorities based on local considerations, including public concern and the impact of school absenteeism and staffing shortages." During the week of April 19, 2009, the CDC activated its Emergency Operations Center (EOC), with RADM Stephen Redd as the Incident Commander, to augment the ongoing investigation of human cases of swine influenza A (H1N1). More than 250 CDC professionals worked from the CDC EOC as part of the agency's response. As of May 4, 2009, the CDC reported that it had deployed 25% of the supplies and medicines in the Strategic National Stockpile to the various states. As of April 29, only the CDC could confirm U.S. swine flu cases. Besser stated during an April 30 press briefing that California and New York had diagnostic test kits, and that the kits would be sent to all states starting the following day. On May 6, the CDC announced that testing kits were now available for all states. It was expected this would generate an increase in the number of confirmed cases as more states began doing their own tests. In the United States, the majority of the 70 National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories do not report the influenza A subtype. [ citation needed ] However, in 2007, human infection with a novel influenzavirus A became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that are unsubtypable with standard methods and reagents. The new strain responsible for this outbreak was one such virus. [ citation needed ]Initially the CDC had issued a recommendation that schools close for as long as two weeks if a student catches swine flu. Some school districts closed all schools if a single child was classified as probable. On May 5 the CDC retracted its advice stating that schools that were closed based on previous CDC guidance related to this outbreak may reopen. By that time at least 726 schools nationwide serving more than 480,000 students had closed for at least some period of time. The CDC amended its advice, citing new information on disease severity and the limiting effectiveness of school closure as a control measure. The new advice given stated, "Decisions about school closure should be at the discretion of local authorities based on local considerations, including public concern and the impact of school absenteeism and staffing shortages." The Food and Drug Administration (FDA) authorized emergency use of medicines and diagnostic tests for flu. (FDA is part of Department of Health and Human Services.) The FDA stated it was also responding to this threat by: working with other government agencies and manufacturers on a series of issues related to antiviral medications. growing the 2009 H1N1 flu virus and preparing to make vaccine seed lots, which may be used eventually to produce a safe and effective vaccine. helping to prepare reagents needed for vaccine production and coordinating closely with other public health agencies for clinical development and testing. accelerating access to new diagnostic tools for this 2009 H1N1 flu virus On May 6, 2009, the FDA announced that it had approved a new manufacturing facility for seasonal flu vaccine, owned by Sanofi Pasteur, which could also be used for manufacturing a vaccine for the new H1N1 flu strain. The FDA also issued a warning for consumers to be wary of products claiming to cure or prevent swine flu. Secretary Napolitano stated that DHS was the principal federal office for incidents such as the H1N1 flu outbreak, and "Under that role, we have been leading a true collaborative effort." The Department of Homeland Security issued a document, dated November 1, 2005, entitled "National Strategy for Pandemic Influenza", detailing planning for potential pandemics. https://web.archive.org/web/20090507013213/http://www.pandemicflu.gov/plan/federal/pandemic-influenza.pdf The State Department suggested travelers to Mexico stay alert and comply with guidance from Mexican public health officials, but did not impose any travel restrictions on US citizens to Mexico. However, the State Department did recommend US citizens avoid non-essential travel to Mexico. The Department of Agriculture (USDA) reported no swine in the US have been infected so far, but the USDA is monitoring swine across the US for signs of infection. The Department of Commerce sent a letter to Russia and China requesting that those countries lift their ban on American pork products. The Department of Defense (DOD) monitored the swine flu situation and had contingency plans to deal with such outbreaks. As of May 7, 2009, the DOD reported 104 confirmed cases among Armed Forces personnel and their families. DOD maintained a daily summary and map. The Department of Education provided guidance to schools in the US affected by swine flu, as well as precautions to take. Secretary Napolitano stated that DHS was the principal federal office for incidents such as the H1N1 flu outbreak, and "Under that role, we have been leading a true collaborative effort." The Department of Homeland Security issued a document, dated November 1, 2005, entitled "National Strategy for Pandemic Influenza", detailing planning for potential pandemics. https://web.archive.org/web/20090507013213/http://www.pandemicflu.gov/plan/federal/pandemic-influenza.pdfThe State Department suggested travelers to Mexico stay alert and comply with guidance from Mexican public health officials, but did not impose any travel restrictions on US citizens to Mexico. However, the State Department did recommend US citizens avoid non-essential travel to Mexico. The Department of Agriculture (USDA) reported no swine in the US have been infected so far, but the USDA is monitoring swine across the US for signs of infection. The Department of Commerce sent a letter to Russia and China requesting that those countries lift their ban on American pork products. The Department of Defense (DOD) monitored the swine flu situation and had contingency plans to deal with such outbreaks. As of May 7, 2009, the DOD reported 104 confirmed cases among Armed Forces personnel and their families. DOD maintained a daily summary and map. The Department of Education provided guidance to schools in the US affected by swine flu, as well as precautions to take. Schools closed in many states in response to local flu outbreaks. By April 30, 2009, 300 U.S. schools and school districts had announced closures in response to the outbreak, giving 169,000 students time off. On May 4, 2009, about 533 schools in 24 states in the U.S. were closed, affecting about 330,000 students. On September 25, 2009, 42 schools were closed in eight states as the second wave of the pandemic began. On May 5, Kathleen Sebelius stated in a CDC news conference that school closures for single confirmed cases of H1N1 influenza were unnecessary, but that children displaying an influenza-like illness should stay home. Several US airlines waived fees for cancellations and flight changes. At least one cruise line changed itinerary to avoid Mexican ports of call. [ citation needed ]

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Pandemic influenza

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Influenza prevention

Influenza prevention involves taking steps that one can use to decrease their chances of contracting flu viruses, such as the Pandemic H1N1/09 virus , responsible for the 2009 flu pandemic .People who contract influenza are most infective between the second and third days after infection, and infectivity lasts for around ten days. Children are much more infectious than adults and shed virus from just before they develop symptoms until two weeks after infection. The transmission of influenza can be modeled mathematically , which helps predict how the virus will spread in a population. Influenza can be spread in three main ways: The relative importance of these three modes of transmission is unclear, and they may all contribute to the spread of the virus. In the airborne route, the droplets that are small enough for people to inhale are 0.5 to 5 µm in diameter and inhaling just one droplet might be enough to cause an infection. Although a single sneeze releases up to 40,000 droplets, most of these droplets are quite large and will quickly settle out of the air. How long influenza survives in airborne droplets seems to be influenced by the levels of humidity and UV radiation : with low humidity and a lack of sunlight in winter probably aiding its survival. As the influenza virus can persist outside of the body, it can also be transmitted by contaminated surfaces such as banknotes, doorknobs, light switches and other household items. The length of time the virus will persist on a surface varies, with the virus surviving for one to two days on hard, non-porous surfaces such as plastic or metal, for about fifteen minutes from dry paper tissues, and only five minutes on skin. However, if the virus is present in mucus, this can protect it for longer periods. Avian influenza viruses can survive indefinitely when frozen. They are inactivated by heating to 56 °C (133 °F) for a minimum of 60 minutes, as well as by acids (at pH <2). According to the World Health Organization (WHO), the "main route of transmission of the pandemic influenza virus seems to be similar to seasonal influenza , via droplets that are expelled by speaking, sneezing or coughing." One of WHO's recommendations is to "keep your distance from people who show symptoms of influenza-like illness, such as coughing and sneezing (trying to maintain a distance of about 1 metre if possible)." Other WHO recommendations are listed below. The American Centers for Disease Control and Prevention (CDC) agrees that the "spread of novel H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza." The CDC also says that a person may become infected if he or she touches something with flu viruses on it "and then touches his or her eyes, nose, or mouth." Researchers have demonstrated anti-bodies against H1N1 variant influenza in 10 to 7 percent of workers and residents of swine farms in Jiangsu Province, China. Residents of a nearby city did not have detectable anti-bodies to H1N1 variant influenza. According to the World Health Organization (WHO), the "main route of transmission of the pandemic influenza virus seems to be similar to seasonal influenza , via droplets that are expelled by speaking, sneezing or coughing." One of WHO's recommendations is to "keep your distance from people who show symptoms of influenza-like illness, such as coughing and sneezing (trying to maintain a distance of about 1 metre if possible)." Other WHO recommendations are listed below. The American Centers for Disease Control and Prevention (CDC) agrees that the "spread of novel H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza." The CDC also says that a person may become infected if he or she touches something with flu viruses on it "and then touches his or her eyes, nose, or mouth." Researchers have demonstrated anti-bodies against H1N1 variant influenza in 10 to 7 percent of workers and residents of swine farms in Jiangsu Province, China. Residents of a nearby city did not have detectable anti-bodies to H1N1 variant influenza. Reasonably effective ways to reduce the transmission of influenza include good personal health and hygiene habits such as: not touching your eyes, nose or mouth; frequent hand washing (with soap and water, or with alcohol-based hand rubs); covering coughs and sneezes; avoiding close contact with sick people; and staying home yourself if you are sick. Avoiding spitting is also recommended. Although face masks might help prevent transmission when caring for the sick, there is mixed evidence on beneficial effects in the community. Smoking raises the risk of contracting influenza, as well as producing more severe disease symptoms. Thus, according to the laws of mathematical modelling of infectious diseases , smokers raise the exponential growth rates of influenza epidemics and may indirectly be responsible for a large percentage of influenza cases. [ citation needed ] Since influenza spreads through both aerosols and contact with contaminated surfaces, surface sanitizing may help prevent some infections. Alcohol is an effective sanitizer against influenza viruses, while quaternary ammonium compounds can be used with alcohol so that the sanitizing effect lasts for longer. In hospitals, quaternary ammonium compounds and bleach are used to sanitize rooms or equipment that have been occupied by patients with influenza symptoms. At home, this can be done effectively with a diluted chlorine bleach. Social distancing strategies used during past pandemics, such as closing schools, churches and theaters, slowed the spread of the virus but did not have a large effect on the overall death rate. It is uncertain if reducing public gatherings, by for example closing schools and workplaces, will reduce transmission since people with influenza may just be moved from one area to another; such measures would also be difficult to enforce and might be unpopular. When small numbers of people are infected, isolating the sick might reduce the risk of transmission. According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control. The Centers for Disease Control and Prevention (CDCP) recommends that businesses promote and administer annual flu vaccination within the workplace. Additional measures include reducing potential for exposure through increasing awareness of flu symptoms, using good cough and sneeze etiquette, staying home when ill, and frequent hand washing. The Occupational Health and Safety Administration (OSHA) recommends these controls to employers to decrease transmission of influenza in the workplace: Promotion, administration, and easy access to the flu vaccine Encourage sick workers to stay home Hand hygiene and cough etiquette Use airborne infection isolation rooms, when appropriate Ensure properly functioning heating, ventilation, and air conditioning (HVAC) systems Limit transport of infected patients Limit the number of staff who come in contact with flu patients Provide personal protective equipment (PPE) such as gloves, gowns, masks, to health care staff as well as disposal facilities Specific occupations with increased risk of influenza infection include health care, education and child care, air line industry, and agricultural workers. According to the WHO, you can decrease your chance of contracting the flu virus by taking the following steps: Get yourself (or family members age 6 months and older) vaccinated against current strains of influenza, if possible. Keep your distance from people who show symptoms of influenza-like illness, such as coughing and sneezing (trying to maintain a distance of about 1 metre if possible); Clean your hands thoroughly with soap and water, or cleanse them with an alcohol-based hand rub on a regular basis (especially if touching surfaces that are potentially contaminated); Avoid touching your mouth, nose and eyes as much as possible; Reduce the time spent in crowded settings if possible; Improve airflow in your living space by opening windows; Practice good health habits (including adequate sleep, eating nutritious food, and keeping physically active) The CDCP lists these as important ways to lower the risk of transmission: Cover the nose and mouth with a tissue when coughing or sneezing. Throw tissues in the trash after use; Wash hands often with soap and water, especially after coughing or sneezing. Alcohol-based hand cleaners are also effective; Avoid touching the eyes, nose, or mouth. Germs spread this way; Try to avoid close contact with sick people; Those sick with flu-like illness are recommended to stay home for at least 24 hours after their fever is gone, except to get medical care or for other necessities. (The fever should be gone without the use of a fever-reducing medicine.) The sickened are advised to keep away from others as much as possible to avoid making others sick.The Centers for Disease Control and Prevention (CDCP) recommends that businesses promote and administer annual flu vaccination within the workplace. Additional measures include reducing potential for exposure through increasing awareness of flu symptoms, using good cough and sneeze etiquette, staying home when ill, and frequent hand washing. The Occupational Health and Safety Administration (OSHA) recommends these controls to employers to decrease transmission of influenza in the workplace: Promotion, administration, and easy access to the flu vaccine Encourage sick workers to stay home Hand hygiene and cough etiquette Use airborne infection isolation rooms, when appropriate Ensure properly functioning heating, ventilation, and air conditioning (HVAC) systems Limit transport of infected patients Limit the number of staff who come in contact with flu patients Provide personal protective equipment (PPE) such as gloves, gowns, masks, to health care staff as well as disposal facilities Specific occupations with increased risk of influenza infection include health care, education and child care, air line industry, and agricultural workers.According to the WHO, you can decrease your chance of contracting the flu virus by taking the following steps: Get yourself (or family members age 6 months and older) vaccinated against current strains of influenza, if possible. Keep your distance from people who show symptoms of influenza-like illness, such as coughing and sneezing (trying to maintain a distance of about 1 metre if possible); Clean your hands thoroughly with soap and water, or cleanse them with an alcohol-based hand rub on a regular basis (especially if touching surfaces that are potentially contaminated); Avoid touching your mouth, nose and eyes as much as possible; Reduce the time spent in crowded settings if possible; Improve airflow in your living space by opening windows; Practice good health habits (including adequate sleep, eating nutritious food, and keeping physically active) The CDCP lists these as important ways to lower the risk of transmission: Cover the nose and mouth with a tissue when coughing or sneezing. Throw tissues in the trash after use; Wash hands often with soap and water, especially after coughing or sneezing. Alcohol-based hand cleaners are also effective; Avoid touching the eyes, nose, or mouth. Germs spread this way; Try to avoid close contact with sick people; Those sick with flu-like illness are recommended to stay home for at least 24 hours after their fever is gone, except to get medical care or for other necessities. (The fever should be gone without the use of a fever-reducing medicine.) The sickened are advised to keep away from others as much as possible to avoid making others sick.Watch for emergency warning signs that need urgent medical attention. These warning signs include: [ citation needed ] Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Not urinating or no tears when crying Severe or persistent vomiting Not waking up or not interacting Being so irritable that the child does not want to be held Pain or pressure in the chest or abdomen Sudden dizziness Confusion Flu-like symptoms improve but then return with fever and worse cough In the 2009 pandemic, the initial demand for vaccine greatly outstripped the supply. As the 2009 pandemic got underway, the first vaccine to become available in the United States by mid-October 2009 was about 2.2 million doses of the weakened live-virus nasal spray formulation . This form was not then recommended for some of the people who were at highest risk of complications from flu, including pregnant women and people with asthma. [ citation needed ] The attenuated live virus was instead suggested to be used to allow some priority groups like health care workers and healthy children 2 or older, to allow them to be vaccinated immediately. Those to whom the weakened virus might pose a heightened risk were recommended to wait for the release of killed-virus vaccines, which followed weeks to months later. [ citation needed ] Vaccine uptake by the public was very low in the UK, but predicted by greater belief in the vaccine's efficacy and safety and a greater perceived risk of the disease. A survey of Americans done in late June 2009 by the Harvard School of Public Health found that roughly 90% said they would be willing to avoid shopping malls, movie theaters, public transportation, and worship services for more than two weeks if health officials told them to. It also found that parents were worried about closures of schools or day care centers, with 43% saying they would lose pay or have money problems if they had to stay home a week or more because they were sick or had to care for someone. In the UK, the government established a National Pandemic Flu Service with a hotline and website, enabling persons with symptoms to get advice or obtain drugs without first getting a prescription from a doctor. Individuals with increased exposure to animals, especially birds and swine, are at increased risk of variant influenza infection. This includes agricultural workers, as well as residents of farms, individuals who keep swine and/or birds as pets, and animal exhibitors. Variant influenza viruses do not normally infect humans, but when they do cause human infection, the virus can be passed from animals to humans directly, or between humans. Due to human to human transmission, family and close contacts of agricultural workers are at increased risk of influenza as well. Unfortunately, there is also decreased access to health care in agricultural communities which makes prevention and response to influenza outbreaks more difficult. During the 2009 H1N1 pandemic, multiple factors were identified as increasing the vulnerability of agricultural workers and their communities. These factors included substandard housing, immigration status, scape-goating, economic barriers, communication and cultural barriers, and discrimination. Steege et al., found that 75% of agricultural workers were uninsured, making them less likely to receive the flu vaccine and less likely to seek care when ill. Public health recommendations for agricultural communities: surveillance of agricultural workers Inclusion of agricultural workers in prevention efforts and planning Separating ICE from emergency services Increased access to influenza vaccination Risk reduction training (cough etiquette, etc.) PPE use Workplace Sanitation Recommendations for agricultural workers and exhibitors: Influenza vaccination Limit time swine are kept on the fairgrounds to no more than 72 hours Wash hands with soap and water when leaving the barn Restrict food and drink in animal area Do not sleep in animal areas Additional recommendations for visitors to agricultural exhibits: High Risk: Defined as people younger than 5 years, older than 65 years, pregnant women, and people with chronic illnesses. Avoid pigs and swine barns Low Risk: Don't eat, drink, or apply anything to your mouth in pig areas Don't take toys, pacifiers, cups, baby bottles, strollers, or similar items into pig areas Avoid close contact with pigs that look or act ill Use gloves, protective clothing, masks if contact with ill pigs Wash your hands often with soap and running water before and after exposure to pigs. If soap and water are not available, use an alcohol-based hand rub. Watch your pig(s) for signs of illness. Call a veterinarian if you suspect illness. Avoid contact with pigs if you have flu symptoms. Wait until you have been fever-free for 7 days or until you have been without fever for 24 hours without taking temperature-reducing medications; whichever is longer If you become ill, contact a health care provider. Let them know you are higher risk and about any recent exposure to pigs or swine barns. The same medications that are used for seasonal flu can be used for variant virus infection. Defined as people younger than 5 years, older than 65 years, pregnant women, and people with chronic illnesses. Avoid pigs and swine barns Don't eat, drink, or apply anything to your mouth in pig areas Don't take toys, pacifiers, cups, baby bottles, strollers, or similar items into pig areas Avoid close contact with pigs that look or act ill Use gloves, protective clothing, masks if contact with ill pigs Wash your hands often with soap and running water before and after exposure to pigs. If soap and water are not available, use an alcohol-based hand rub. Watch your pig(s) for signs of illness. Call a veterinarian if you suspect illness. Avoid contact with pigs if you have flu symptoms. Wait until you have been fever-free for 7 days or until you have been without fever for 24 hours without taking temperature-reducing medications; whichever is longer If you become ill, contact a health care provider. Let them know you are higher risk and about any recent exposure to pigs or swine barns. The same medications that are used for seasonal flu can be used for variant virus infection.

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Pandemic influenza

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Pandemic Severity Assessment Framework

The Pandemic Severity Assessment Framework ( PSAF ) is an evaluation framework published by the Centers for Disease Control and Prevention in 2016 which uses quadrants to evaluate both the transmissibility and clinical severity of an influenza pandemic and to combine these into an overall impact estimate. Clinical severity is calculated via multiple measures including case fatality rate , case- hospitalization ratios, and deaths-hospitalizations ratios, while viral transmissibility is measured via available data among secondary household attack rates, school attack rates, workplace attack rates, community attack rates, rates of emergency department and outpatient visits for influenza-like illness . The PSAF superseded the 2007 linear Pandemic Severity Index (PSI), which assumed 30% spread and measured case fatality rate (CFR) to assess the severity and evolution of the pandemic. The United States Centers for Disease Control and Prevention (CDC) adopted the PSAF as its official pandemic severity assessment tool in 2014, and it was the official pandemic severity assessment tool listed in the CDC's National Pandemic Strategy at the time of the COVID-19 pandemic . Historically, measures of influenza pandemic severity were based on the case fatality rate. However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because: Deaths may lag several weeks behind cases, making the case fatality rate an underestimate The total number of cases may not be known, making the case fatality rate an overestimate A single case fatality rate for the entire population may obscure the effect on vulnerable sub-populations, such as children, the elderly, those with chronic conditions, and members of certain racial and ethnic minorities Fatalities alone may not account for the full effects of the pandemic, such as absenteeism or demand on healthcare services To account for the limitations of measuring the case fatality rate alone, the PSAF rates severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. Each dimension can be measured using more than one measure, which are scaled to facilitate comparison. Having multiple measures for each dimension offers flexibility to choose a measure that is readily available, accurate, and representative of the impact of the pandemic. It also allows comparison across measures for a more complete understanding of the severity. The framework gives commentary on the strengths and limitations of various measures of clinical severity and transmissibility as well as guidelines for scaling them. It also provides examples of assessing past pandemics using the framework. The original documentation for the PSAF includes the following as potential measures of transmissibility: The original documentation for the PSAF includes the following as potential measures of clinical severity: The original documentation for the PSAF includes the following as potential measures of transmissibility: The original documentation for the PSAF includes the following as potential measures of clinical severity: The original developers of the PSAF provided a model for the number of hypothetical deaths in the United States 2010 population of an influenza pandemic using the PSAF. While the axes of the PSAF are scaled measures of transmissibility and clinical severity, this model uses the case-fatality ratio instead of the scaled measure of clinical severity and the cumulative incidence of infection instead of the scaled measure of transmissibility. During its development, the PSAF was applied to past influenza pandemics and epidemics, resulting in the following assessments: A team of Brazilian researchers preliminarily assessed the severity of the COVID-19 pandemic using the PSAF in April 2020 based on Chinese data as at 11 February 2020. In their preliminary assessment, they rate COVID-19's scaled transmissibility at 5 and its scaled clinical severity at 4 to 7, placing the COVID-19 pandemic in the "very high severity" quadrant. This preliminary assessment ranks the COVID-19 pandemic as the most severe pandemic since the 1918 influenza pandemic. During its development, the PSAF was applied to past influenza pandemics and epidemics, resulting in the following assessments: A team of Brazilian researchers preliminarily assessed the severity of the COVID-19 pandemic using the PSAF in April 2020 based on Chinese data as at 11 February 2020. In their preliminary assessment, they rate COVID-19's scaled transmissibility at 5 and its scaled clinical severity at 4 to 7, placing the COVID-19 pandemic in the "very high severity" quadrant. This preliminary assessment ranks the COVID-19 pandemic as the most severe pandemic since the 1918 influenza pandemic.

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Pandemic influenza

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Influenza A virus subtype H3N8

H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs. It is the main cause of equine influenza and is also known as equine influenza virus . In 2011, it was reported to have been found in seals. Cats have been experimentally infected with the virus, leading to clinical signs, shedding of the virus and infection of other cats. In 2022 and 2023, three people in China were infected with H3N8, with one fatality, marking the first time a human has died from this strain of flu. Equine influenza (EI) is a highly contagious respiratory disease of horses and related animals such as donkeys, mules and zebras (collectively known as equines). Equine influenza is caused by a type A influenza virus in the family Orthomyxoviridae (genus Influenzavirus). Transmission of the equine influenza virus (EIV) to humans has not occurred during outbreaks of the disease in horses. A lineage of H3N8 has been found to infect humans, with the first two cases in China in April and May 2022, and a third case in March 2023, which was the first death. In 1963, the H3N8 (A/equine/2/Miami/63) subtype created an epidemic of equine influenza in Miami and subsequently spread throughout North and South America and Europe, creating massive outbreaks during 1964 and 1965. Since 1963, the H3N8 virus has drifted along a single lineage at a rate of 0.8 amino acid substitutions per year. Between 1978 and 1981, there were widespread epidemics of the A/equine/2 strain throughout the US and Europe despite the development of vaccines. Since the late 1980s, evolution of the H3N8 virus has diverged into two families: an "American-like" lineage and a "European-like" lineage. A 1997 study found H3N8 was responsible for over one quarter of the influenza infections in wild ducks. H3N8 has been suggested as a possible cause of the 1889–1890 pandemic in humans, and also another epidemic in 1898–1900. Before the identification of H3N8 as a possible cause of the 1889 pandemic, the H2N2 subtype was suggested. At this point, it is not possible to identify the virus for either the 1889 or 1900 outbreak with certainty. Equine influenza virus (H3N8) can be spread by a few different routes. The ultimate source of the virus is respiratory tract secretions. Coughing horses can release the virus into the air, where it can spread up to 30–50 metres. It can also be spread by direct contact between horses, or indirectly via a person's hands or clothing, or on inanimate objects (e.g. buckets, tack, twitches). However, the virus doesn't survive outside of a horse for long The virus is delicate within the environment and easily killed by heat, cold, desiccation , and disinfectants . The virus multiplies in epithelial cells of upper respiratory tract. Dispersed by aerosol droplets when horse coughs or exhales. The virus can survive in the environment, on different surfaces, for up to 48 hours. Spread of the disease has been associated with the movement of people, pets, horse equipment and tack where proper biosecurity procedures have not been followed Subclinical infection with virus shedding can occur in vaccinated horses, particularly where there is a mismatch between the vaccine strains and the virus strains circulating in the field. Such infections contribute to the spread of the disease. The time from when a horse gets exposed to the time when it gets sick. It is quite short for equine influenza: typically 1–3 days and up to 7 days. This makes disease control easier, as infected horses can be identified sooner, meaning that appropriate control measures can be enacted more quickly. Diseases that have very long incubation periods can be more difficult to control. Aerosolized influenza virus is inhaled and embeds in the respiratory mucosa, of the upper and lower respiratory tract. The virus is attracted to the glycoproteins and mucopolysaccharides of the mucus coating the respiratory mucosa. If the infecting dose of virus is high, abundant viral neuraminidase breaks down the mucosal layer, allowing access of the virus to the underlying epithelial cells. The virus then attaches to epithelial cells through binding of the hemagglutinin spike to the N-acetylneuraminic acid receptor on the cell. The virus then enters the cell by endocytosis into the cell cytoplasm where it replicates to produce new virions that are released back into the respiratory tract by budding from the infected cell. The virus disperses throughout the trachea and bronchial tree within 3 days, causing hyperemia, edema, necrosis, desquamation, and focal erosion. Viremia is rare, but is possible if the virus crosses the basement membrane and enters the circulation, potentially causing inflammation of skeletal and cardiac muscle (myositis and myocarditis), encephalitic signs, and limb edema Fever of 102.5–105.0 °F (39.2–40.6 °C) , frequent dry cough for several weeks, 'drippy' nose with discharge and secondary bacterial infection are some of the clinical signs of Equine influenza virus infection. isolation of influenza virus from nasopharyngeal and or large rise in antibody titer in equine-1 or 2 serum can be used as diagnosis in horses. Other clinical findings may include a serous or light mucoid nasal discharge, epiphora , tender but rarely swollen submandibular lymph nodes, hyperemia of nasal and conjunctival mucosa, tachypnea , tachycardia , limb edema, muscle soreness and stiffness. The length of time a horse can spread the virus after being infected. It is a very important concept, because horses can still infect other horses after they have gotten over their own illness. Viruses that are shed for long periods of time after a horse gets better are much harder to control. Horses tend to be most infectious (i.e. shedding the most virus) in the first 24–48 hours after they develop a fever, but they can shed the virus for up to 7–10 days after their signs of illness disappear.

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Pandemic influenza

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1918 flu pandemic in India

1918 flu pandemic in India was the outbreak of an unusually deadly influenza pandemic in British India between 1918 and 1920 as a part of the worldwide Spanish flu pandemic. Also referred to as the Bombay Influenza or the Bombay Fever in India, the pandemic is believed to have killed up to 17–18 million people in the country, the most among all countries. David Arnold (2019) estimates at least 12 million dead, about 5% of the population. The decade between 1911 and 1921 was the only census period in which India's population fell, mostly due to devastation of the Spanish flu pandemic. The death toll in India's British-ruled districts was 13.88 million. The pandemic broke out in Bombay in June 1918, with one of the possible routes being via ships carrying troops returning from the First World War in Europe. The outbreak then spread across the country from west and south to east and north, reaching the whole of the country by August. It hit different parts of the country in three waves with the second wave being the highest in mortality rate. The death rate peaked in the last week of September 1918 in Bombay, in the middle of October in Madras , and in the middle of November in Calcutta . The outbreak most severely affected younger people in the age group of 20–40, with women disproportionately impacted. According to the Sanitary Commissioner's report for 1918, the maximum death toll in a week exceeded 200 deaths in both Bombay and Madras. The spread of the disease was exacerbated by a failed monsoon and the resultant famine-like conditions, that had left people underfed and weak, and forced them to move into densely populated cities. As a result of the severity of the outbreak, the year 1919 saw a reduction of births by around 30 percent. The population growth of India during the decade of 1911–1921 was 1.2%, the lowest among all decades under the British Raj . In his memoirs the Hindi poet, Suryakant Tripathi , wrote " Ganga was swollen with dead bodies." The sanitary commissioner's report for 1918 also noted that all rivers across India were clogged up with bodies, because of a shortage of firewood for cremation. Mahatma Gandhi , the leader of India's independence struggle, was also infected by the virus. The pandemic had a significant influence in the freedom movement in the country. The healthcare system in the country was unable to meet the sudden increase in demands for medical attention. The consequent toll of death and misery, and economic fallout brought about by the pandemic led to an increase in emotion against colonial rule.

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Pandemic influenza

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2009 swine flu pandemic in Australia

Australia had 37,537 confirmed cases of H1N1 Influenza 2009 (Human Swine Influenza) and 191 deaths reported by Department of Health but only 77 deaths reported by the Australian Bureau of Statistics. The actual numbers are much larger, as only serious cases warranted being tested and treated at the time. Suspected cases have not been reported by the Department of Health and Ageing since 18 May 2009 because they were changing too quickly to report. Sources say that as many as 1600 Australians may have actually died as a result of this virus. On 23rd of May 2009 the federal government classified the outbreak as CONTAIN phase except in Victoria where it was escalated to the SUSTAIN phase on 3rd of June 2009. This gave government authorities permission to close schools in order to slow the spread of the disease. On 17 June 2009 the Department of Health and Ageing introduced a new phase called PROTECT. This modified the response to focus on people with high risk of complications from the disease. Testing at airports was discontinued. The national stockpile of antiviral drugs were no longer made available to people with the flu unless there were more than mild symptoms or a high risk of dying. There are on average 2,500–3,000 deaths every year as a result of seasonal influenza in Australia. An estimated 1 billion are infected seasonally throughout the world. By 18 December 2009 in Australia, 37,537 swine flu tests yielded positive results and the confirmed death toll of people infected with swine flu was 191. The first case of swine flu in Australia was reported on 9 May 2009 in a 33-year-old woman from Queensland when she touched down from a flight from Los Angeles to Brisbane . Although it was confirmed to be not infectious (coming out as a "weak but positive result"), family members and people who were sitting close to her during the flight were contacted and urged to seek immediate medical attention if they began to show flu-like symptoms. On 24 May Queensland confirmed its second case. 41 deaths were recorded in Queensland. The first person to die in Queensland was a 38-year-old woman on 15 July at the Mater Hospital Pimlico . In Victoria 2,440 cases were reported, including 24 deaths. An 11-year-old boy, and later his 2 brothers, were confirmed on 20 May to carry the virus. Victorian health authorities closed Clifton Hill Primary School for two days on 21 May, initially, after the three brothers returned to the school from a trip to Disneyland . Another case delayed the reopening of the school until Thursday 28 May 2009. On 23 May about 22 year-nine students of Mill Park Secondary College were given anti-viral Tamiflu after one of their classmates was diagnosed with swine flu. The same situation happened for students in year nine at the University High School in Parkville and also for the Melton campus of Mowbray College after a year 10 student contracted the virus . A 35-year-old man from Colac died on 20 June 2009 at Maroondah Hospital after going to Colac Hospital the previous day. On 23 June 2009, the second swine flu related death in Victoria was reported, that of a 50-year-old woman at the Peter MacCallum Cancer Centre . A third death was reported on 25 June. Two more deaths were reported on the weekend of 27 and 28 June. Two more deaths were reported on 1 July, which included a 3-year-old. Four more deaths were recorded on 8 July. In New South Wales 51 deaths were recorded. The first confirmed death in New South Wales occurred on 29 June and a second man died on 3 July. South Australia recorded 28 deaths, plus a 'clinical positive' where the test was inconclusive and, after swine-flu-like symptoms were reported, Tamiflu was administered, thus making a future positive confirmation unlikely. Adelaide high schools Eynesbury Senior College and Blackfriars Priory School closed for a week. The first confirmed death from swine flu in South Australia was a 26-year-old Aboriginal man from Kiwirrkurra Community in the Western Desert of Western Australia who died in Royal Adelaide Hospital on 19 June. The Australian Capital Territory recorded 2 deaths and confirmed 920 cases by 28 August 2009. Two of the earliest casualties contracted the disease while on the Pacific Dawn cruise ship. The first death in the ACT occurred on 28 July 2009. During the last week of July 2009, Radford College's year 12 cohort was asked to stay home, after a spike of influenza through the year. [ citation needed ] There were 27 confirmed deaths in Western Australia . On 26 June 2009, a 26-year-old woman was the first person to die in the state. A 26-year-old Western Australian man died in Adelaide on 19 June. Tasmania recorded seven deaths. The first person to die in Tasmania was an 85-year-old woman who died in Royal Hobart Hospital on 5 July. The Northern Territory confirmed the first infection of a person on 30 May 2009. By this time, six people in the territory had died. The first person in the Territory to die from the epidemic was a man in his early 50s who died at the Royal Darwin Hospital on 6 July. In Victoria 2,440 cases were reported, including 24 deaths. An 11-year-old boy, and later his 2 brothers, were confirmed on 20 May to carry the virus. Victorian health authorities closed Clifton Hill Primary School for two days on 21 May, initially, after the three brothers returned to the school from a trip to Disneyland . Another case delayed the reopening of the school until Thursday 28 May 2009. On 23 May about 22 year-nine students of Mill Park Secondary College were given anti-viral Tamiflu after one of their classmates was diagnosed with swine flu. The same situation happened for students in year nine at the University High School in Parkville and also for the Melton campus of Mowbray College after a year 10 student contracted the virus . A 35-year-old man from Colac died on 20 June 2009 at Maroondah Hospital after going to Colac Hospital the previous day. On 23 June 2009, the second swine flu related death in Victoria was reported, that of a 50-year-old woman at the Peter MacCallum Cancer Centre . A third death was reported on 25 June. Two more deaths were reported on the weekend of 27 and 28 June. Two more deaths were reported on 1 July, which included a 3-year-old. Four more deaths were recorded on 8 July. In New South Wales 51 deaths were recorded. The first confirmed death in New South Wales occurred on 29 June and a second man died on 3 July. South Australia recorded 28 deaths, plus a 'clinical positive' where the test was inconclusive and, after swine-flu-like symptoms were reported, Tamiflu was administered, thus making a future positive confirmation unlikely. Adelaide high schools Eynesbury Senior College and Blackfriars Priory School closed for a week. The first confirmed death from swine flu in South Australia was a 26-year-old Aboriginal man from Kiwirrkurra Community in the Western Desert of Western Australia who died in Royal Adelaide Hospital on 19 June. The Australian Capital Territory recorded 2 deaths and confirmed 920 cases by 28 August 2009. Two of the earliest casualties contracted the disease while on the Pacific Dawn cruise ship. The first death in the ACT occurred on 28 July 2009. During the last week of July 2009, Radford College's year 12 cohort was asked to stay home, after a spike of influenza through the year. [ citation needed ]There were 27 confirmed deaths in Western Australia . On 26 June 2009, a 26-year-old woman was the first person to die in the state. A 26-year-old Western Australian man died in Adelaide on 19 June. Tasmania recorded seven deaths. The first person to die in Tasmania was an 85-year-old woman who died in Royal Hobart Hospital on 5 July. The Northern Territory confirmed the first infection of a person on 30 May 2009. By this time, six people in the territory had died. The first person in the Territory to die from the epidemic was a man in his early 50s who died at the Royal Darwin Hospital on 6 July. The swine flu also affected some Australians internationally: Pacific Dawn cruise ship swine flu scare On the 25th of May, approximately 3 hours after getting off the boat, a case of swine flu was reported on board. This caused a spike in the number of cases, going up much more rapidly than before, and somehow causing "Case 1" (see above). The number of cases was around 20 before the scare but grew to well over 15,000. This cruise ship is believed to have caused almost half of the cases in SA, the WA case, and the TAS case. It also caused a flu scare in New Caledonia . [ citation needed ]In 2008, the Australian government prepared for a possible flu pandemic by creating the Australian Health Management Plan for Pandemic Influenza (AHMPPI). When the outbreak hit its peak in 2009, this plan went into action. [ citation needed ] The plan followed six steps: The Australian Government had a stockpile of 40 million surgical grade face masks. However, stocks of face masks in pharmacies were depleted due to personal purchases. The World Health Organization Influenza Centre in North Melbourne was attempting to develop a vaccine for swine flu by growing the live virus as found in California, in chicken embryos. The first one-litre batch of vaccine was announced to be ready on 29 June 2009 by the University of Queensland , but would not be available for use until it was registered as safe with the regulatory authority. A Commonwealth Health hotline for Swine Influenza was set up on Australian phone number 1802007 by the Department of Health and Ageing . The Australian Government set up a health emergency web site. Daily tallies of suspected cases were given. The Tasmanian Government set up a Tasmanian Action Plan for Human Influenza Pandemic . The Queensland Government had an action plan prepared in 2008 and a business continuity plan in 2006. The Australian Capital Territory Chief Medical Officer, Dr Charles Guest, claimed that procedures and systems were very good to detect and respond to the disease outbreak. South Australia nominated eight hospitals to handle the flu: Royal Adelaide, Flinders Medical Centre or Women's and Children's Hospital, Berri, Mount Gambier, Port Lincoln, Whyalla or Port Augusta. The Victorian Government Department of Human Services had a nurse on call to answer questions on the topic. CSL Limited started to produce a vaccine to immunize against swine flu. The Australian Government ordered ten million doses of the new vaccine. In Melbourne, seven special clinics for influenza opened on 29 May. Per recommendations by the World Health Organization, Australia decided against closing their borders during the DELAY phase of the outbreak. There were also no restrictions of travel to and from countries where outbreaks were occurring. However, starting on 30 April, thermal imaging was applied to passenger arrivals at international airports and arriving passengers were required to fill in a card. Customs officers checked aeroplane cabins prior to disembarkation of passengers to look for people with flu symptoms. The Australian Government created a nationwide campaign project that encouraged Australians to take up healthy practices such as adequate hand washing, avoiding people who were more susceptible to death from the flu, and getting the vaccine that was available. This was done in media, print, and radio forms so that it could reach the most people as possible. Another main focus of the Australian campaign was to dispel myths about the flu in order to provide citizens with the most factual information available at the time. A large scale immunization effort against swine flu started on Monday 28 September 2009. [ citation needed ] At the peak of the outbreak, Australia had a stockpile of 8.7 million doses of Tamiflu and Relenza to combat the virus. In 2008, the Australian government prepared for a possible flu pandemic by creating the Australian Health Management Plan for Pandemic Influenza (AHMPPI). When the outbreak hit its peak in 2009, this plan went into action. [ citation needed ] The plan followed six steps: The Australian Government had a stockpile of 40 million surgical grade face masks. However, stocks of face masks in pharmacies were depleted due to personal purchases. The World Health Organization Influenza Centre in North Melbourne was attempting to develop a vaccine for swine flu by growing the live virus as found in California, in chicken embryos. The first one-litre batch of vaccine was announced to be ready on 29 June 2009 by the University of Queensland , but would not be available for use until it was registered as safe with the regulatory authority. A Commonwealth Health hotline for Swine Influenza was set up on Australian phone number 1802007 by the Department of Health and Ageing . The Australian Government set up a health emergency web site. Daily tallies of suspected cases were given. The Tasmanian Government set up a Tasmanian Action Plan for Human Influenza Pandemic . The Queensland Government had an action plan prepared in 2008 and a business continuity plan in 2006. The Australian Capital Territory Chief Medical Officer, Dr Charles Guest, claimed that procedures and systems were very good to detect and respond to the disease outbreak. South Australia nominated eight hospitals to handle the flu: Royal Adelaide, Flinders Medical Centre or Women's and Children's Hospital, Berri, Mount Gambier, Port Lincoln, Whyalla or Port Augusta. The Victorian Government Department of Human Services had a nurse on call to answer questions on the topic. CSL Limited started to produce a vaccine to immunize against swine flu. The Australian Government ordered ten million doses of the new vaccine. In Melbourne, seven special clinics for influenza opened on 29 May. Per recommendations by the World Health Organization, Australia decided against closing their borders during the DELAY phase of the outbreak. There were also no restrictions of travel to and from countries where outbreaks were occurring. However, starting on 30 April, thermal imaging was applied to passenger arrivals at international airports and arriving passengers were required to fill in a card. Customs officers checked aeroplane cabins prior to disembarkation of passengers to look for people with flu symptoms. The Australian Government created a nationwide campaign project that encouraged Australians to take up healthy practices such as adequate hand washing, avoiding people who were more susceptible to death from the flu, and getting the vaccine that was available. This was done in media, print, and radio forms so that it could reach the most people as possible. Another main focus of the Australian campaign was to dispel myths about the flu in order to provide citizens with the most factual information available at the time. A large scale immunization effort against swine flu started on Monday 28 September 2009. [ citation needed ] At the peak of the outbreak, Australia had a stockpile of 8.7 million doses of Tamiflu and Relenza to combat the virus. In a 2011 article in the Emerging Health Threats Journal, Peter Collignon commented that the media frequently compared the outbreaks to the 1918 flu pandemic that infected 500 million people and killed tens of millions. Widespread public fear of a similar number of deaths led to "Emergency Departments and doctor surgeries being overwhelmed" with requests for antiviral drugs, jeopardising the supply for the highest risk patients.

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Pandemic influenza

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1977 Russian flu

The 1977 Russian flu was an influenza pandemic that was first reported by the Soviet Union in 1977 and lasted until 1979. The outbreak in northern China started in May 1977, slightly earlier than that in the Soviet Union. The pandemic mostly affected a population younger than 25 or 26 years of age, and was described as mild. It was caused by an H1N1 flu strain which highly resembled a virus strain circulating worldwide from 1946 to 1957. Genetic analysis and several unusual characteristics of the 1977 Russian flu have prompted many researchers to say that the virus was released to the public through a laboratory accident, or resulted from a live-vaccine trial escape. In May 1977, an outbreak of flu took place in northern China including Liaoning , Jilin and Tianjin . The strain was isolated and determined by Chinese researchers to be H1N1 , which mostly affected students in middle and primary schools who lacked immunity to H1N1 virus. Clinical symptoms were relatively mild. Other areas in mainland China and British Hong Kong were also affected in the following months. In the same year, the H1N1 strain was detected in Siberia shortly after the outbreak in China, and then spread rapidly across the Soviet Union , which was the first country to report the outbreak to the World Health Organization (the People's Republic of China was not a member of WHO until 1981 ). Therefore, the pandemic was named "Russian flu". In 1977, the Russian flu hit the United Kingdom . The virus reached the United States in January 1978. The first outbreak in the U.S. was reported in a high school in Cheyenne , where the clinical attack rate was more than 70% but involved solely students. Even though infections were seen in schools and military bases throughout the U.S., there were few reports of infection in people older than 26, and the death rate in affected individuals was low. Since late 1977, the H1N1 strain has begun to co-circulate with the H3N2 strain in humans, as seasonal flu . There have been various H1N1 strains . The 1918 Spanish flu was caused by an H1N1 strain, and H1N1 strains afterwards became endemic and circulated around the world until 1957, when they all but vanished. (There were some isolated reports of other H1N1 strains such as the one in the early 1960s. ) H1N1 reappeared in 1977 and the strain of the Russian flu was almost identical to one that had been isolated in 1950. This feature of the 1977 strain has been interpreted as pointing towards an anthropogenic origin of the virus, and the pandemic is the only documented human epidemic believed to result from research activity. The Russian flu was relatively benign. In 1977, Chinese researchers found uneven attack rates among different groups of students, as well as many mild and asymptomatic infections. In the United States , some researchers estimate the influenza mortality rate (not the infection fatality rate or the case fatality rate ) around 5 in every 100,000 population, less than that of the typical seasonal influenza (~6 in every 100,000 population). Most of the infected people were under the age of 26 or 25, presumably because older people retained immunity from exposure to previous H1N1 strains. Contradicting these descriptions, one review article proposed that 700,000 people died due to the Russian flu pandemic worldwide and that the virus was "Identical with "Spanish flu" virus".

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Pandemic influenza

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1782 Influenza pandemic

In 1782 a pandemic of influenza emerged in Asia before spreading worldwide. It resulted in severe disruption to society in Europe and the Americas as it disabled populations with sudden and widespread illness, with the flu even affecting dogs and cats. Occurring at the height of the Age of Enlightenment , was noted by contemporary physicians, generals, and medical researchers who sought to explain the infectious causes and treatments for influenza.The pandemic reached Europe in the spring, and European ships quickly diffused influenza across the continent. Flu spread rapidly and noticeable epidemics rarely lingered in a communities for longer than 2 months. Flu was widespread in London during the pandemic of 1782. Influenza inhibited the British Army's post-war activities as well. Admiral Kempenfelt set sail from Spithead with a squadron of ships on 2 May, among them the Goliath. By the 29th the flu had spread so thoroughly through the Goliath and other vessels' crews that the whole squadron was obliged to return to port in England. Dr. Grant describes that the epidemic raged By August 1782, Dr. Grant had written that the flu "still rages in parts of France." Flu spread to Scandinavia during the springs. Ship traffic spread the flu quickly along the coasts. On the Island of Tjörn deaths spiked from 9 in April to 25 in May, well above average mortalities for summer. Up to 40,000 people fell sick in one day in Saint Petersburg . Flu was widespread in London during the pandemic of 1782. Influenza inhibited the British Army's post-war activities as well. Admiral Kempenfelt set sail from Spithead with a squadron of ships on 2 May, among them the Goliath. By the 29th the flu had spread so thoroughly through the Goliath and other vessels' crews that the whole squadron was obliged to return to port in England. Dr. Grant describes that the epidemic ragedBy August 1782, Dr. Grant had written that the flu "still rages in parts of France." Flu spread to Scandinavia during the springs. Ship traffic spread the flu quickly along the coasts. On the Island of Tjörn deaths spiked from 9 in April to 25 in May, well above average mortalities for summer. Up to 40,000 people fell sick in one day in Saint Petersburg .

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Pandemic influenza

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1789–1790 influenza epidemic

Between the fall of 1789 and the spring of 1790, influenza occurred extensively throughout the United States and North America more broadly. First reported in the southern United States in September, it spread throughout the northern states in October and November, appeared about the same time in the West Indies , and reached as far north as Nova Scotia before the end of 1789. In the spring of 1790, a renewed epidemic developed, almost as universal as the first but more often fatal.By the late 18th century, influenza was a relatively common feature in North America. The disease was definitively recorded on the continent for the first time in 1647. The Western Hemisphere was then involved in several pandemics during the 1700s, including one in 1761 which, notably, might have begun in North America. Prior to 1789, the last major epidemic of influenza on the continent was in the spring of 1781. In March 1788, influenza broke out in Saint Petersburg and in Kherson (at the time part of Russia), as well as in Warsaw , where even the King of Poland was afflicted. It then spread westward across Europe throughout the year, evidently appearing last in Geneva , in October. Following this epidemic of 1788, influenza was generally not reported again until the latter half of 1789, though there is perhaps some evidence that the disease may have been present in some form during the intervening period. For example, Luigi Careno, an Italian doctor based in Vienna , details a "very epidemic catarrh " [lower-alpha 1] that prevailed in the city during the winter of 1789; William Eden , then Ambassador to Spain for George III , describes "a new influenza of colds" prevailing in March 1789 in Madrid , where his ambassadorship was at that time coming to an end; and, according to the College of Physicians of Philadelphia , influenza was epidemic in that city in April 1789. Beyond these accounts, however, the major histories of the disease on the whole make no mention of influenza during this time. The connection between the epidemic of 1788 and that of 1789–1790, if any, is not entirely clear. Historically, the two were often considered separately, though some authors have considered them together as a single epidemic period, both in older and more modern sources. According to Noah Webster , some accounts place the earliest outbreaks of the disease in Canada, though there is very little, if any, evidence of this, beyond Webster's reporting. Influenza was present in Georgia in September, and at least one report suggests that it was also prevalent in South Carolina ( Charleston ) by the end of the month and soon after. It appeared in Virginia at the end of September. The flu broke out sometime in September in New York City, then the capital of the young nation, where it quickly assumed epidemic proportions. John Fenno , publisher of the influential Gazette of the United States , contracted the disease in early October. On the 9th, he wrote of "an almost universal Complaint here of a severe Cold"; the next day, he came to the conclusion that the city was "afflicted with the Influenza—I can call it by no other name." In a letter to his sister, dated 12 October, George Washington describes "[a] sort of epidemical cold" that had pervaded the city but which he had thus far been able to avoid. This "Epidemick cold", as Abigail Adams called it, soon invaded the household of Richmond Hill , on Manhattan Island , afflicting the whole Adams family (except for John Quincy and the vice president , who had departed for Braintree (now Quincy ), Massachusetts , on the 5th and the 12th, respectively). On 15 October, the president set out on his tour of the New England states . Philadelphia was stricken at the beginning of October, or perhaps even as early as late September; the outbreak there, in any case, developed subsequently to the one in New York. William Currie, a notable physician in the city, speculated that the disease could have been brought, at least in part, by some Friends of Philadelphia Yearly Meeting that had come from New York for the body's annual meeting, which that year was held from 28 September to 3 October. On the other hand, Benjamin Rush , another eminent doctor of Philadelphia, suggested that members of the 1st Congress , arriving in the city from New York after the close of the first session on 29 September, might have played a part in introducing the disease. They were, perhaps not surprisingly, "much indisposed with colds", and though they attributed their general sickness "to… fatigue and the night air ", the immense and rapid spread of the disease shortly thereafter made it clear that it must have been the one "so well known of late years, by the name of the Influenza." To observers such as Rush, the disease was considered to have spread from these cities "in all directions". It was general in Fairfield County, Connecticut , at the beginning of October. On the 12th or 15th, it broke out in Hartford , where Webster lived at that time. On the 19th, he left the town for Boston and arrived there the next day. By the last week of October, the disease was prevalent in the interior of Pennsylvania , as well as in New Jersey , Delaware , and Maryland ; by the first week of November, it was prevalent in all the states of New England ( Connecticut , Rhode Island , Massachusetts, and New Hampshire ). On 24 October, Washington arrived in Boston, escorted by Lieutenant Governor Samuel Adams and the Executive Council , amid much fanfare. A massive crowd had gathered in a procession to welcome him. According to Webster, who began to develop symptoms the day of his own arrival in the city, influenza was not yet present among the inhabitants at this time. Nonetheless, by the 26th, Washington had contracted it, and soon thereafter it broke out more noticeably throughout the city. This timing was not lost on the people, who quickly took to calling the prevailing ailment by such names as the "Washington influenza", the "Washington cold", and the "President's cough", suspecting they had caught it during the celebrations. By the start of November, the city of Boston was "universally seized" by the flu, such that, according to at least one report, nine-tenths of its inhabitants had already fallen ill. Influenza began to appear in the West Indies around the same time as it did in the northern United States, in October and November. It broke out in Westmoreland Parish, Jamaica , around 20 October and in Nassau , on the island of New Providence , in the last week of October. The disease "raged universally" on the islands of Sint Eustatius , Saint Kitts , and Dominica at this time as well. In early November, some trade vessels arrived at the ports of St. George's and Grenville Bay in Grenada from these afflicted islands. These ships, it was believed, introduced the flu into the island, as they were navigated by enslaved sailors who were "very much afflicted with it". These sailors, returning to the homes of their respective enslavers, were lodged alongside others of their station, who at that time were "in a perfect state of health". In less than a week, however, all were stricken; and, over the course of a fortnight, influenza became universally prevalent in St. George's. This same month, it was similarly universal in Saint Croix and in Kingston . In these parts, similar to on the mainland, great numbers were afflicted, but the illness was mostly not very fatal. In Kingston, it struck "all classes of people, and few escaped it"; generally mild, it occasioned few or no fatalities. Similarly, in St. George's, it "indiscriminately" infected both whites and blacks, with "very few" escaping it; and, in Westmoreland Parish, it "seized great numbers of all ages, colours, and sexes", even among the young and healthy. Nonetheless, it did still have the potential to be severe during this initial epidemic. In the parish, the disease indeed "visited successively, less or more, every estate and settlement," but it could vary from place to place: Some were affected very severely, while others experienced milder outbreaks, even a few hardly perceiving its presence at all. The epidemic continued to rage throughout the United States in November, by which time the whole country was in its grip. As The Vermont Gazette reported for 9 November, "So universal a complaint of bad colds perhaps never prevailed in America before, as at present." Its publishers, in the same report, express their apologies for the abbreviated edition that day, as the flu had afflicted their own families, as it had so many already. In Boston, where the disease "rag'd universally", felling entire families, normal business faltered in the middle of the month on account of the outbreak; bread production, for example, declined to less than a quarter of its typical output. On 1 November, John Adams wrote to his wife Abigail from Braintree that "[t]he Influenza is here as general as it was at N. York", informing her that their youngest son, Thomas , had come down with it there but was improving. Abigail would later receive word from her sister, Mary Smith Cranch (with whom Thomas was staying at this time), that the whole household was "much indisposed with colds but nobody quite sick". On the 22nd, Abigail wrote to her eldest son, John Quincy, admonishing him for not writing at all after leaving New York the month before. As it turned out, John had contracted "a severe cold" upon his arrival in Braintree on 9 October, which confined him for 2 or 3 days; only later did he conclude that it had likely been the influenza. Writing to his mother on 5 December, he describes the sickness as "almost universal in this State", as it had been since his own infection. He recounts having been scolded for singularly maintaining relatively good health during this time, "while all the world were more or less diseased." In December, the flu prevailed in Nova Scotia and, near the end of the month, appeared in Saint Lucia . It appeared among the Spanish settlements in South America that winter. In the United States, it persisted into December. The epidemic in Philadelphia lasted about six or seven weeks. On the whole, it took six to eight weeks for the disease to spread across the whole country. The epidemic reportedly afflicted Native Americans with some severity. According to the land surveyor Andrew Ellicott , influenza struck those in the Niagara region "with peculiar force"; they apparently considered the attendant cough of the illness to be "so new and so irritating" that they attributed it to "witchcraft." In Grenada, a shift in the presentation of the disease began to be observed in the middle of December. While earlier in the fall it had been a more catarrhal (i.e., coldlike) affliction, it soon took on a more inflammatory character, marked "by the violence, obscurity, and insidious nature of its symptoms" when it first appeared on some estates. This change "increased to a most alarming degree, and rendered the disorder… extremely dangerous and fatal." By mid-January 1790, the disease was ubiquitous on the island again. A similar shift was noted around this time in Virginia, where over the winter an inflammatory ailment began to appear, associated with symptoms so much more severe that there was some uncertainty whether it was influenza at all. The disease "was much more fatal" and often resistant to treatment. In the north, influenza evidently reappeared first along the Hudson River the last week of March, in Albany and in Vermont, where it laid entire families low for weeks. In early April it appeared along the Connecticut River , to the east, and from there in the northeast apparently spread in a southwest direction. By 5 April, the incidence of "bad colds and inflammatory disorders" was reportedly already greater than it had ever been in southern Vermont. Indeed, it was quite clear by mid-April that the influenza had returned to the United States. It was once again "universal" in Hartford; it was "raging" in Norwich , where it was noted to have assumed "redoubled violence"; and in Boston, it had reportedly already stricken one-third of its citizens. By the end of the month, it was prevalent in Providence . On 22 April, Sarah Livingston Jay received word of the outbreak in Hartford and, the next day, wrote to her husband John , at that time the Chief Justice of the Supreme Court , urging him to be careful while in the town, where he was at that time as part of his duties as Circuit Justice for the Eastern Circuit . Although he would not receive this message until the following month, he would have needed no warning: On 26 April, the Chief Justice wrote in his diary that "almost every Family here is down with the Influenza— some old people have died with it". Indeed, by the end of the month, "little business" was getting done at all on account of the outbreak besides tending to the sick. Influenza reappeared in New York City sometime in April as well. Alexander Hamilton , the Secretary of the Treasury , contracted the disease there at some point, such that, by 6 May, he had been confined by the illness for "several Weeks". Late in April, influenza again invaded the estate of Richmond Hill, which Abigail Adams described as "a mere Hospital", each member confined to a different chamber with some sort of affliction; the vice president, however, again evaded infection. James Madison , then a U.S. representative from Virginia, received a "full measure" of it during this time as well. The disease broke out in Philadelphia the last week of April, though it remained generally mild during its prevalence there over the next month, in contrast to other places. It was already declining in Boston by the first week of May but continued to spread and prevail in many parts throughout the month. It reappeared "with additional violence" in the Maryland and Virginia counties situated upon those states' "fertile rivers" and, similarly, was reported to be "mortally dangerous" in Delaware around this time. In New Hampshire, the disease crippled normal business operations in Portsmouth , where it had broken out the month before; it prevailed in Exeter (the state's capital at this time) and neighboring towns, with some mortality reported. A report out of Newburyport, Massachusetts , near the end of May described mortality from the flu, as well as other illnesses in that area, as having surpassed that of any other time in memory. Influenza prevailed with particular force in New York City throughout the month of May. On 8 May, Abigail Adams wrote to her sister Mary that she had recovered from what she had come to learn was the influenza, noting that "almost every Body throughout the whole city are labouring under it." Sarah Livingston Jay made a similar observation around the same time in a letter to her husband, describing the disease as "as prevalent here at present as it was last Autumn" and informing him of illnesses in the family, including that of his brother and sister-in-law. That same day, 10 May, she was seized with the influenza herself. She wrote John again a few days later, updating him of her condition, as well as that of their 1-year-old son William , who had been "likewise very ill" by then but was recovering. The Chief Justice was in Portsmouth, on the last leg of his circuit duties, when he received his wife's letters on the 20th. He was swift to respond to the latter of the two, expressing his "anxiety" at the news of his loved ones' illnesses. He promised her that nothing would delay his return to her and stated his expectation of their reunion by mid-June, for he remained as yet well, despite the unfortunate timing of his circuit that spring: "The whole Country has been sick, and indeed is much so yet." Indeed, in the town of Braintree, sickness was as prevalent as anywhere. In a message dated 16 May, Mary Smith Cranch wrote to her sister in New York describing the many illnesses in the family, including that of her daughter Elizabeth, whose "whole Family been sick Baby & all with this new distemper". She relates, "In short I hardly know of a Person who has not been or is now sick" — but it was not just the epidemic influenza: "I believe there have been more People who have had the measles in this Parish than ever had them before & many of them attackd with the Influenzy at the same time." Several of their acquaintances had died of the flu already. It would take until the 25th for Mary to complete her letter, sickness by then still front of mind. Having returned from Hingham , she writes that "Uncles Family every root & Branch of it were weak haveing just had the influenzy" and, similarly, that the whole family of their sister Elizabeth had been ill but were by then improved. As for her daughter Elizabeth, about whom Abigail had been much worried, and Elizabeth's young son, Mary could share the news of at least their recoveries, in contrast to so many adults and infants alike in her vicinity, whether on account of the measles or the influenza. The epidemic continued in the nation's capital. The city was, according to Senator Richard Henry Lee of Virginia, "a perfect Hospital—few are well & many very sick." Responding to her sister in a letter dated 30 May, Abigail Adams expressed her "dread" surrounding a disconcerting piece of news that had come to public light earlier that month: The president had fallen mortally ill. It is unclear when exactly Washington contracted the influenza. The first indication of illness from the president himself was recorded in his diary, in which he wrote for Sunday, 9 May 1790, "Indisposed with a bad cold, and at home all day writing letters on private business." However, there is reason to believe that he contracted the disease as early as early April or even late March. Richard Bland Lee , a U.S. representative from Virginia, wrote to David Stuart , a doctor and close advisor to the president, on 6 April that "the President has been unwell for a few days past." Over the next several days Washington's health was apparently in decline, as attested by George Clymer , a representative from Pennsylvania, who described the "great deal of anxiety" surrounding the president's health at this time. On 20 April, Washington set out on a tour of Long Island , apparently in an effort to regain his failing health. Several observers attest that this outing did improve his condition somewhat, but the relief was only temporary. On 7 May, William Maclay , a U.S. Senator from Pennsylvania, wrote to Benjamin Rush that the president had "nearly lost his hearing" on account of his illness. Two days later, he was afflicted with that "bad cold" and was unable to leave his bed on the 10th, on which day he "was taken with a peripneumony , of threatening appearance", according to Thomas Jefferson . In these first days of Washington's more severe condition, an effort was made to conceal his illness from the public, "as a general allarm may have proved injurious to the present State of the government", as Abigail Adams explained to the Massachusetts physician Cotton Tufts . After a minor improvement on 12 May, the president's health declined quickly to a critical point on 15 May. By the next day, there were "no hopes of his recovery." Around this time, despite the attempts at secrecy, Washington's indisposition had become relatively well known in New York City and Philadelphia, and the press was quick to pick up on the story. There was, reportedly, "Universal Gloom throughout this Country"; in South Carolina, citizens were "greatly alarmed of late at the Account of the President's ill-health." Concern for the president emanated from across the country and even as far as Europe. During this time, Washington was attended mainly by the eminent New York City physician Samuel Bard , who had previously tended to the president in June 1789 during another period of severe illness, which ultimately required the removal of a tumor from his left leg. While afflicted with the influenza, Washington suffered from "a very high fever" and "expectorate[d] blood". On 16 May, as his physicians considered him to be on the verge of death, he "was Seazd with Hicups & rattling in his Throat". He was administered James 's fever powder, and this evidently "produced a happy Effect". That evening, he began to sweat copiously, a change that was thought to relieve his cough and improve his breathing. By the next morning, Washington was much improved, and he was considered to be out of danger. By 20 May, his fever had reportedly broken, and he was back on his feet by the 22nd. News of the president's recovery inspired universal relief, including among "friends to America" in Paris, and the press reported on this positive development. While Washington was ill, his presidential duties were carried out by William Jackson , one of his personal secretaries. Although he had improved enough to move about his room freely by the 23rd, it seems he did not resume his official duties until the end of the month. On 3 June, Washington wrote to the Marquis de Lafayette that he was "recovered, except in point of strength." He shared the advice of his physicians to exercise more and focus less on business, but he considered it "essential to accomplish whatever I have undertaken (though reluctantly) to the best of my abilities." It was not until 24 June that he resumed making entries in his diary, around which time he added an entry for 10 May, the first day of his confinement, that described the beginning of his "severe illness … which left me in a convalescent state for several weeks after the violence of it had passed". In a letter to David Stuart dated 15 June, Washington reflected on the state of his health. He noted, "Within the last twelve months I have undergone more, and severer sickness than thirty preceding years afflicted me with, put it altogether", and expressed his fear that a third bout of illness might "put me to sleep with my fathers". Although thankful for how much he had improved, he could "still feel the remains of the violent affection of my lungs—The cough, the pain in my breast, and shortness in breathing not having entirely left me." The epidemic in Philadelphia declined about the first week of June, and it was apparently over in most parts of the country by the summer. [lower-alpha 2] Among the more notable victims of this epidemic was Theodorick Bland , a U.S. representative from Virginia, who succumbed to the disease on 1 June, becoming the first member of the House of Representatives to die while in office . He was succeeded by William Branch Giles , who was elected in a special election in July and took office on 7 December 1790. The outbreak beginning in the fall of 1789 was considered to be one of the most extensive epidemics ever to affect the country by that time. Although influenza had appeared in North America in previous outbreaks, there were some who believed that this visitation was one of an entirely novel disease. It generated much attention and many theories, in particular as to whether it was contagious . Its effect on society inspired a resolution passed by the New Haven County Medical Society on 1 July, for example, that called for an investigation by "any person, whether of the faculty or not," into several key questions regarding the nature of the disease. These included: "1st. Whether any sensible change in the air, or seasons, gave rise to the late Catarrhal Epidemic? 2d. Whether the disease was contagious? 3d. Whether a humoral pathology , is necessary to account for the origin, or first phenomena of any disease?" The epidemiology of the disease was described in several accounts written in the years following the outbreak. Some of these include: This epidemic came at the beginning of what has been termed a "pandemic era" (starting in 1788), in which global influenza activity remained apparently elevated for nearly 20 years (i.e., until 1806). During this time, and extending until 1889 , influenza activity in the Western Hemisphere seemed disconnected from that in Europe and the rest of the Eastern Hemisphere . After the spring of 1790, influenza recurred several times in epidemic fashion in the United States over the next few years. It returned in the fall of 1790 "with great violence in many places", such as Essex County, Virginia , and continued to prevail in the winter and spring of 1791 in places such as Philadelphia and New York. It was again "prevalent in several parts of the continent" in the fall of 1792 and throughout the northeast in the fall of 1793. By the late 18th century, influenza was a relatively common feature in North America. The disease was definitively recorded on the continent for the first time in 1647. The Western Hemisphere was then involved in several pandemics during the 1700s, including one in 1761 which, notably, might have begun in North America. Prior to 1789, the last major epidemic of influenza on the continent was in the spring of 1781. In March 1788, influenza broke out in Saint Petersburg and in Kherson (at the time part of Russia), as well as in Warsaw , where even the King of Poland was afflicted. It then spread westward across Europe throughout the year, evidently appearing last in Geneva , in October. Following this epidemic of 1788, influenza was generally not reported again until the latter half of 1789, though there is perhaps some evidence that the disease may have been present in some form during the intervening period. For example, Luigi Careno, an Italian doctor based in Vienna , details a "very epidemic catarrh " [lower-alpha 1] that prevailed in the city during the winter of 1789; William Eden , then Ambassador to Spain for George III , describes "a new influenza of colds" prevailing in March 1789 in Madrid , where his ambassadorship was at that time coming to an end; and, according to the College of Physicians of Philadelphia , influenza was epidemic in that city in April 1789. Beyond these accounts, however, the major histories of the disease on the whole make no mention of influenza during this time. The connection between the epidemic of 1788 and that of 1789–1790, if any, is not entirely clear. Historically, the two were often considered separately, though some authors have considered them together as a single epidemic period, both in older and more modern sources. According to Noah Webster , some accounts place the earliest outbreaks of the disease in Canada, though there is very little, if any, evidence of this, beyond Webster's reporting. Influenza was present in Georgia in September, and at least one report suggests that it was also prevalent in South Carolina ( Charleston ) by the end of the month and soon after. It appeared in Virginia at the end of September. The flu broke out sometime in September in New York City, then the capital of the young nation, where it quickly assumed epidemic proportions. John Fenno , publisher of the influential Gazette of the United States , contracted the disease in early October. On the 9th, he wrote of "an almost universal Complaint here of a severe Cold"; the next day, he came to the conclusion that the city was "afflicted with the Influenza—I can call it by no other name." In a letter to his sister, dated 12 October, George Washington describes "[a] sort of epidemical cold" that had pervaded the city but which he had thus far been able to avoid. This "Epidemick cold", as Abigail Adams called it, soon invaded the household of Richmond Hill , on Manhattan Island , afflicting the whole Adams family (except for John Quincy and the vice president , who had departed for Braintree (now Quincy ), Massachusetts , on the 5th and the 12th, respectively). On 15 October, the president set out on his tour of the New England states . Philadelphia was stricken at the beginning of October, or perhaps even as early as late September; the outbreak there, in any case, developed subsequently to the one in New York. William Currie, a notable physician in the city, speculated that the disease could have been brought, at least in part, by some Friends of Philadelphia Yearly Meeting that had come from New York for the body's annual meeting, which that year was held from 28 September to 3 October. On the other hand, Benjamin Rush , another eminent doctor of Philadelphia, suggested that members of the 1st Congress , arriving in the city from New York after the close of the first session on 29 September, might have played a part in introducing the disease. They were, perhaps not surprisingly, "much indisposed with colds", and though they attributed their general sickness "to… fatigue and the night air ", the immense and rapid spread of the disease shortly thereafter made it clear that it must have been the one "so well known of late years, by the name of the Influenza." To observers such as Rush, the disease was considered to have spread from these cities "in all directions". It was general in Fairfield County, Connecticut , at the beginning of October. On the 12th or 15th, it broke out in Hartford , where Webster lived at that time. On the 19th, he left the town for Boston and arrived there the next day. By the last week of October, the disease was prevalent in the interior of Pennsylvania , as well as in New Jersey , Delaware , and Maryland ; by the first week of November, it was prevalent in all the states of New England ( Connecticut , Rhode Island , Massachusetts, and New Hampshire ). On 24 October, Washington arrived in Boston, escorted by Lieutenant Governor Samuel Adams and the Executive Council , amid much fanfare. A massive crowd had gathered in a procession to welcome him. According to Webster, who began to develop symptoms the day of his own arrival in the city, influenza was not yet present among the inhabitants at this time. Nonetheless, by the 26th, Washington had contracted it, and soon thereafter it broke out more noticeably throughout the city. This timing was not lost on the people, who quickly took to calling the prevailing ailment by such names as the "Washington influenza", the "Washington cold", and the "President's cough", suspecting they had caught it during the celebrations. By the start of November, the city of Boston was "universally seized" by the flu, such that, according to at least one report, nine-tenths of its inhabitants had already fallen ill. Influenza began to appear in the West Indies around the same time as it did in the northern United States, in October and November. It broke out in Westmoreland Parish, Jamaica , around 20 October and in Nassau , on the island of New Providence , in the last week of October. The disease "raged universally" on the islands of Sint Eustatius , Saint Kitts , and Dominica at this time as well. In early November, some trade vessels arrived at the ports of St. George's and Grenville Bay in Grenada from these afflicted islands. These ships, it was believed, introduced the flu into the island, as they were navigated by enslaved sailors who were "very much afflicted with it". These sailors, returning to the homes of their respective enslavers, were lodged alongside others of their station, who at that time were "in a perfect state of health". In less than a week, however, all were stricken; and, over the course of a fortnight, influenza became universally prevalent in St. George's. This same month, it was similarly universal in Saint Croix and in Kingston . In these parts, similar to on the mainland, great numbers were afflicted, but the illness was mostly not very fatal. In Kingston, it struck "all classes of people, and few escaped it"; generally mild, it occasioned few or no fatalities. Similarly, in St. George's, it "indiscriminately" infected both whites and blacks, with "very few" escaping it; and, in Westmoreland Parish, it "seized great numbers of all ages, colours, and sexes", even among the young and healthy. Nonetheless, it did still have the potential to be severe during this initial epidemic. In the parish, the disease indeed "visited successively, less or more, every estate and settlement," but it could vary from place to place: Some were affected very severely, while others experienced milder outbreaks, even a few hardly perceiving its presence at all. The epidemic continued to rage throughout the United States in November, by which time the whole country was in its grip. As The Vermont Gazette reported for 9 November, "So universal a complaint of bad colds perhaps never prevailed in America before, as at present." Its publishers, in the same report, express their apologies for the abbreviated edition that day, as the flu had afflicted their own families, as it had so many already. In Boston, where the disease "rag'd universally", felling entire families, normal business faltered in the middle of the month on account of the outbreak; bread production, for example, declined to less than a quarter of its typical output. On 1 November, John Adams wrote to his wife Abigail from Braintree that "[t]he Influenza is here as general as it was at N. York", informing her that their youngest son, Thomas , had come down with it there but was improving. Abigail would later receive word from her sister, Mary Smith Cranch (with whom Thomas was staying at this time), that the whole household was "much indisposed with colds but nobody quite sick". On the 22nd, Abigail wrote to her eldest son, John Quincy, admonishing him for not writing at all after leaving New York the month before. As it turned out, John had contracted "a severe cold" upon his arrival in Braintree on 9 October, which confined him for 2 or 3 days; only later did he conclude that it had likely been the influenza. Writing to his mother on 5 December, he describes the sickness as "almost universal in this State", as it had been since his own infection. He recounts having been scolded for singularly maintaining relatively good health during this time, "while all the world were more or less diseased." In December, the flu prevailed in Nova Scotia and, near the end of the month, appeared in Saint Lucia . It appeared among the Spanish settlements in South America that winter. In the United States, it persisted into December. The epidemic in Philadelphia lasted about six or seven weeks. On the whole, it took six to eight weeks for the disease to spread across the whole country. The epidemic reportedly afflicted Native Americans with some severity. According to the land surveyor Andrew Ellicott , influenza struck those in the Niagara region "with peculiar force"; they apparently considered the attendant cough of the illness to be "so new and so irritating" that they attributed it to "witchcraft." In Grenada, a shift in the presentation of the disease began to be observed in the middle of December. While earlier in the fall it had been a more catarrhal (i.e., coldlike) affliction, it soon took on a more inflammatory character, marked "by the violence, obscurity, and insidious nature of its symptoms" when it first appeared on some estates. This change "increased to a most alarming degree, and rendered the disorder… extremely dangerous and fatal." By mid-January 1790, the disease was ubiquitous on the island again. A similar shift was noted around this time in Virginia, where over the winter an inflammatory ailment began to appear, associated with symptoms so much more severe that there was some uncertainty whether it was influenza at all. The disease "was much more fatal" and often resistant to treatment. In the north, influenza evidently reappeared first along the Hudson River the last week of March, in Albany and in Vermont, where it laid entire families low for weeks. In early April it appeared along the Connecticut River , to the east, and from there in the northeast apparently spread in a southwest direction. By 5 April, the incidence of "bad colds and inflammatory disorders" was reportedly already greater than it had ever been in southern Vermont. Indeed, it was quite clear by mid-April that the influenza had returned to the United States. It was once again "universal" in Hartford; it was "raging" in Norwich , where it was noted to have assumed "redoubled violence"; and in Boston, it had reportedly already stricken one-third of its citizens. By the end of the month, it was prevalent in Providence . On 22 April, Sarah Livingston Jay received word of the outbreak in Hartford and, the next day, wrote to her husband John , at that time the Chief Justice of the Supreme Court , urging him to be careful while in the town, where he was at that time as part of his duties as Circuit Justice for the Eastern Circuit . Although he would not receive this message until the following month, he would have needed no warning: On 26 April, the Chief Justice wrote in his diary that "almost every Family here is down with the Influenza— some old people have died with it". Indeed, by the end of the month, "little business" was getting done at all on account of the outbreak besides tending to the sick. Influenza reappeared in New York City sometime in April as well. Alexander Hamilton , the Secretary of the Treasury , contracted the disease there at some point, such that, by 6 May, he had been confined by the illness for "several Weeks". Late in April, influenza again invaded the estate of Richmond Hill, which Abigail Adams described as "a mere Hospital", each member confined to a different chamber with some sort of affliction; the vice president, however, again evaded infection. James Madison , then a U.S. representative from Virginia, received a "full measure" of it during this time as well. The disease broke out in Philadelphia the last week of April, though it remained generally mild during its prevalence there over the next month, in contrast to other places. It was already declining in Boston by the first week of May but continued to spread and prevail in many parts throughout the month. It reappeared "with additional violence" in the Maryland and Virginia counties situated upon those states' "fertile rivers" and, similarly, was reported to be "mortally dangerous" in Delaware around this time. In New Hampshire, the disease crippled normal business operations in Portsmouth , where it had broken out the month before; it prevailed in Exeter (the state's capital at this time) and neighboring towns, with some mortality reported. A report out of Newburyport, Massachusetts , near the end of May described mortality from the flu, as well as other illnesses in that area, as having surpassed that of any other time in memory. Influenza prevailed with particular force in New York City throughout the month of May. On 8 May, Abigail Adams wrote to her sister Mary that she had recovered from what she had come to learn was the influenza, noting that "almost every Body throughout the whole city are labouring under it." Sarah Livingston Jay made a similar observation around the same time in a letter to her husband, describing the disease as "as prevalent here at present as it was last Autumn" and informing him of illnesses in the family, including that of his brother and sister-in-law. That same day, 10 May, she was seized with the influenza herself. She wrote John again a few days later, updating him of her condition, as well as that of their 1-year-old son William , who had been "likewise very ill" by then but was recovering. The Chief Justice was in Portsmouth, on the last leg of his circuit duties, when he received his wife's letters on the 20th. He was swift to respond to the latter of the two, expressing his "anxiety" at the news of his loved ones' illnesses. He promised her that nothing would delay his return to her and stated his expectation of their reunion by mid-June, for he remained as yet well, despite the unfortunate timing of his circuit that spring: "The whole Country has been sick, and indeed is much so yet." Indeed, in the town of Braintree, sickness was as prevalent as anywhere. In a message dated 16 May, Mary Smith Cranch wrote to her sister in New York describing the many illnesses in the family, including that of her daughter Elizabeth, whose "whole Family been sick Baby & all with this new distemper". She relates, "In short I hardly know of a Person who has not been or is now sick" — but it was not just the epidemic influenza: "I believe there have been more People who have had the measles in this Parish than ever had them before & many of them attackd with the Influenzy at the same time." Several of their acquaintances had died of the flu already. It would take until the 25th for Mary to complete her letter, sickness by then still front of mind. Having returned from Hingham , she writes that "Uncles Family every root & Branch of it were weak haveing just had the influenzy" and, similarly, that the whole family of their sister Elizabeth had been ill but were by then improved. As for her daughter Elizabeth, about whom Abigail had been much worried, and Elizabeth's young son, Mary could share the news of at least their recoveries, in contrast to so many adults and infants alike in her vicinity, whether on account of the measles or the influenza. The epidemic continued in the nation's capital. The city was, according to Senator Richard Henry Lee of Virginia, "a perfect Hospital—few are well & many very sick." Responding to her sister in a letter dated 30 May, Abigail Adams expressed her "dread" surrounding a disconcerting piece of news that had come to public light earlier that month: The president had fallen mortally ill. It is unclear when exactly Washington contracted the influenza. The first indication of illness from the president himself was recorded in his diary, in which he wrote for Sunday, 9 May 1790, "Indisposed with a bad cold, and at home all day writing letters on private business." However, there is reason to believe that he contracted the disease as early as early April or even late March. Richard Bland Lee , a U.S. representative from Virginia, wrote to David Stuart , a doctor and close advisor to the president, on 6 April that "the President has been unwell for a few days past." Over the next several days Washington's health was apparently in decline, as attested by George Clymer , a representative from Pennsylvania, who described the "great deal of anxiety" surrounding the president's health at this time. On 20 April, Washington set out on a tour of Long Island , apparently in an effort to regain his failing health. Several observers attest that this outing did improve his condition somewhat, but the relief was only temporary. On 7 May, William Maclay , a U.S. Senator from Pennsylvania, wrote to Benjamin Rush that the president had "nearly lost his hearing" on account of his illness. Two days later, he was afflicted with that "bad cold" and was unable to leave his bed on the 10th, on which day he "was taken with a peripneumony , of threatening appearance", according to Thomas Jefferson . In these first days of Washington's more severe condition, an effort was made to conceal his illness from the public, "as a general allarm may have proved injurious to the present State of the government", as Abigail Adams explained to the Massachusetts physician Cotton Tufts . After a minor improvement on 12 May, the president's health declined quickly to a critical point on 15 May. By the next day, there were "no hopes of his recovery." Around this time, despite the attempts at secrecy, Washington's indisposition had become relatively well known in New York City and Philadelphia, and the press was quick to pick up on the story. There was, reportedly, "Universal Gloom throughout this Country"; in South Carolina, citizens were "greatly alarmed of late at the Account of the President's ill-health." Concern for the president emanated from across the country and even as far as Europe. During this time, Washington was attended mainly by the eminent New York City physician Samuel Bard , who had previously tended to the president in June 1789 during another period of severe illness, which ultimately required the removal of a tumor from his left leg. While afflicted with the influenza, Washington suffered from "a very high fever" and "expectorate[d] blood". On 16 May, as his physicians considered him to be on the verge of death, he "was Seazd with Hicups & rattling in his Throat". He was administered James 's fever powder, and this evidently "produced a happy Effect". That evening, he began to sweat copiously, a change that was thought to relieve his cough and improve his breathing. By the next morning, Washington was much improved, and he was considered to be out of danger. By 20 May, his fever had reportedly broken, and he was back on his feet by the 22nd. News of the president's recovery inspired universal relief, including among "friends to America" in Paris, and the press reported on this positive development. While Washington was ill, his presidential duties were carried out by William Jackson , one of his personal secretaries. Although he had improved enough to move about his room freely by the 23rd, it seems he did not resume his official duties until the end of the month. On 3 June, Washington wrote to the Marquis de Lafayette that he was "recovered, except in point of strength." He shared the advice of his physicians to exercise more and focus less on business, but he considered it "essential to accomplish whatever I have undertaken (though reluctantly) to the best of my abilities." It was not until 24 June that he resumed making entries in his diary, around which time he added an entry for 10 May, the first day of his confinement, that described the beginning of his "severe illness … which left me in a convalescent state for several weeks after the violence of it had passed". In a letter to David Stuart dated 15 June, Washington reflected on the state of his health. He noted, "Within the last twelve months I have undergone more, and severer sickness than thirty preceding years afflicted me with, put it altogether", and expressed his fear that a third bout of illness might "put me to sleep with my fathers". Although thankful for how much he had improved, he could "still feel the remains of the violent affection of my lungs—The cough, the pain in my breast, and shortness in breathing not having entirely left me." It is unclear when exactly Washington contracted the influenza. The first indication of illness from the president himself was recorded in his diary, in which he wrote for Sunday, 9 May 1790, "Indisposed with a bad cold, and at home all day writing letters on private business." However, there is reason to believe that he contracted the disease as early as early April or even late March. Richard Bland Lee , a U.S. representative from Virginia, wrote to David Stuart , a doctor and close advisor to the president, on 6 April that "the President has been unwell for a few days past." Over the next several days Washington's health was apparently in decline, as attested by George Clymer , a representative from Pennsylvania, who described the "great deal of anxiety" surrounding the president's health at this time. On 20 April, Washington set out on a tour of Long Island , apparently in an effort to regain his failing health. Several observers attest that this outing did improve his condition somewhat, but the relief was only temporary. On 7 May, William Maclay , a U.S. Senator from Pennsylvania, wrote to Benjamin Rush that the president had "nearly lost his hearing" on account of his illness. Two days later, he was afflicted with that "bad cold" and was unable to leave his bed on the 10th, on which day he "was taken with a peripneumony , of threatening appearance", according to Thomas Jefferson . In these first days of Washington's more severe condition, an effort was made to conceal his illness from the public, "as a general allarm may have proved injurious to the present State of the government", as Abigail Adams explained to the Massachusetts physician Cotton Tufts . After a minor improvement on 12 May, the president's health declined quickly to a critical point on 15 May. By the next day, there were "no hopes of his recovery." Around this time, despite the attempts at secrecy, Washington's indisposition had become relatively well known in New York City and Philadelphia, and the press was quick to pick up on the story. There was, reportedly, "Universal Gloom throughout this Country"; in South Carolina, citizens were "greatly alarmed of late at the Account of the President's ill-health." Concern for the president emanated from across the country and even as far as Europe. During this time, Washington was attended mainly by the eminent New York City physician Samuel Bard , who had previously tended to the president in June 1789 during another period of severe illness, which ultimately required the removal of a tumor from his left leg. While afflicted with the influenza, Washington suffered from "a very high fever" and "expectorate[d] blood". On 16 May, as his physicians considered him to be on the verge of death, he "was Seazd with Hicups & rattling in his Throat". He was administered James 's fever powder, and this evidently "produced a happy Effect". That evening, he began to sweat copiously, a change that was thought to relieve his cough and improve his breathing. By the next morning, Washington was much improved, and he was considered to be out of danger. By 20 May, his fever had reportedly broken, and he was back on his feet by the 22nd. News of the president's recovery inspired universal relief, including among "friends to America" in Paris, and the press reported on this positive development. While Washington was ill, his presidential duties were carried out by William Jackson , one of his personal secretaries. Although he had improved enough to move about his room freely by the 23rd, it seems he did not resume his official duties until the end of the month. On 3 June, Washington wrote to the Marquis de Lafayette that he was "recovered, except in point of strength." He shared the advice of his physicians to exercise more and focus less on business, but he considered it "essential to accomplish whatever I have undertaken (though reluctantly) to the best of my abilities." It was not until 24 June that he resumed making entries in his diary, around which time he added an entry for 10 May, the first day of his confinement, that described the beginning of his "severe illness … which left me in a convalescent state for several weeks after the violence of it had passed". In a letter to David Stuart dated 15 June, Washington reflected on the state of his health. He noted, "Within the last twelve months I have undergone more, and severer sickness than thirty preceding years afflicted me with, put it altogether", and expressed his fear that a third bout of illness might "put me to sleep with my fathers". Although thankful for how much he had improved, he could "still feel the remains of the violent affection of my lungs—The cough, the pain in my breast, and shortness in breathing not having entirely left me." The epidemic in Philadelphia declined about the first week of June, and it was apparently over in most parts of the country by the summer. [lower-alpha 2] Among the more notable victims of this epidemic was Theodorick Bland , a U.S. representative from Virginia, who succumbed to the disease on 1 June, becoming the first member of the House of Representatives to die while in office . He was succeeded by William Branch Giles , who was elected in a special election in July and took office on 7 December 1790. The outbreak beginning in the fall of 1789 was considered to be one of the most extensive epidemics ever to affect the country by that time. Although influenza had appeared in North America in previous outbreaks, there were some who believed that this visitation was one of an entirely novel disease. It generated much attention and many theories, in particular as to whether it was contagious . Its effect on society inspired a resolution passed by the New Haven County Medical Society on 1 July, for example, that called for an investigation by "any person, whether of the faculty or not," into several key questions regarding the nature of the disease. These included: "1st. Whether any sensible change in the air, or seasons, gave rise to the late Catarrhal Epidemic? 2d. Whether the disease was contagious? 3d. Whether a humoral pathology , is necessary to account for the origin, or first phenomena of any disease?" The epidemiology of the disease was described in several accounts written in the years following the outbreak. Some of these include: This epidemic came at the beginning of what has been termed a "pandemic era" (starting in 1788), in which global influenza activity remained apparently elevated for nearly 20 years (i.e., until 1806). During this time, and extending until 1889 , influenza activity in the Western Hemisphere seemed disconnected from that in Europe and the rest of the Eastern Hemisphere . After the spring of 1790, influenza recurred several times in epidemic fashion in the United States over the next few years. It returned in the fall of 1790 "with great violence in many places", such as Essex County, Virginia , and continued to prevail in the winter and spring of 1791 in places such as Philadelphia and New York. It was again "prevalent in several parts of the continent" in the fall of 1792 and throughout the northeast in the fall of 1793. This epidemic came at the beginning of what has been termed a "pandemic era" (starting in 1788), in which global influenza activity remained apparently elevated for nearly 20 years (i.e., until 1806). During this time, and extending until 1889 , influenza activity in the Western Hemisphere seemed disconnected from that in Europe and the rest of the Eastern Hemisphere . After the spring of 1790, influenza recurred several times in epidemic fashion in the United States over the next few years. It returned in the fall of 1790 "with great violence in many places", such as Essex County, Virginia , and continued to prevail in the winter and spring of 1791 in places such as Philadelphia and New York. It was again "prevalent in several parts of the continent" in the fall of 1792 and throughout the northeast in the fall of 1793. The influenza was frequently noted for its universality, being perhaps more prevalent in the fall than in the spring. It struck communities suddenly, and great numbers were attacked all at once. "Few" were described as escaping it, though young children were apparently much less affected. In the eastern parts of Virginia, for example, "scarce one in a thousand escap[ed] it" in the fall; in Boston, 90 percent of the population were reportedly afflicted. It attacked both men and women and spared no particular race, though Native Americans may have been affected to a greater degree. In the spring, it was similarly extremely prevalent. There is some evidence that those who were attacked in the fall were later spared in the spring, though apparent reinfections were not uncommon. Notably, Washington, Abigail Adams, and Noah Webster, for example, were evidently twice afflicted. Such repeat attacks sometimes occurred even within the same epidemic: Benjamin Rush describes the striking case of one woman who was stricken first in Philadelphia, again in New York, and yet again upon returning to Philadelphia. During its initial prevalence in the fall, the influenza was frequently noted to be mild, albeit utterly pervasive, with fatalities generally only rarely reported. In Norfolk, Virginia, for example, when it came to the few fatalities that did occur, they were attributed more to "improper management" than the severity of the illness itself. In Philadelphia, it was deadly mostly only to older people, as well as those "previously debilitated by consumptive complaints" (i.e., lung diseases , or pulmonary tuberculosis in particular); alcoholics seemed also to be a risk group. The disease was reported as being more fatal, however, along the "sea-shore" of the country (i.e., the East Coast ), as well as in the southern states. Its "ravages" in Maryland, for example, were especially apparent in Caroline County , a particularly disease-ridden area at this time. In Charleston, one of the earliest places affected, "numbers" were described as having been infected and being, by mid-October, "dangerously ill". The second epidemic was noted early on as being of a different nature from the first and was frequently described as "fatal" and "violent" in many places, specifically in contrast to the first epidemic. New York City, for example, was severely affected. According to William Maclay, "many" in New York died every day from the disease during its prevalence in May. Abigail Adams wrote at this time that the flu had "in many places been very mortal, particularly upon long Island." In Newburyport, Massachusetts, it was reported at the end of May that "[t]he number of deaths, from influenza and other disorders in this part of the country, exceeds that of any other period now remembered." Indeed, in Boston, although most deaths occurred among the elderly, all age groups saw notable increases in mortality during the epidemic. Philadelphia, on the other hand, was apparently not much more severely affected than it had been in the fall. The influenza was frequently noted for its universality, being perhaps more prevalent in the fall than in the spring. It struck communities suddenly, and great numbers were attacked all at once. "Few" were described as escaping it, though young children were apparently much less affected. In the eastern parts of Virginia, for example, "scarce one in a thousand escap[ed] it" in the fall; in Boston, 90 percent of the population were reportedly afflicted. It attacked both men and women and spared no particular race, though Native Americans may have been affected to a greater degree. In the spring, it was similarly extremely prevalent. There is some evidence that those who were attacked in the fall were later spared in the spring, though apparent reinfections were not uncommon. Notably, Washington, Abigail Adams, and Noah Webster, for example, were evidently twice afflicted. Such repeat attacks sometimes occurred even within the same epidemic: Benjamin Rush describes the striking case of one woman who was stricken first in Philadelphia, again in New York, and yet again upon returning to Philadelphia. During its initial prevalence in the fall, the influenza was frequently noted to be mild, albeit utterly pervasive, with fatalities generally only rarely reported. In Norfolk, Virginia, for example, when it came to the few fatalities that did occur, they were attributed more to "improper management" than the severity of the illness itself. In Philadelphia, it was deadly mostly only to older people, as well as those "previously debilitated by consumptive complaints" (i.e., lung diseases , or pulmonary tuberculosis in particular); alcoholics seemed also to be a risk group. The disease was reported as being more fatal, however, along the "sea-shore" of the country (i.e., the East Coast ), as well as in the southern states. Its "ravages" in Maryland, for example, were especially apparent in Caroline County , a particularly disease-ridden area at this time. In Charleston, one of the earliest places affected, "numbers" were described as having been infected and being, by mid-October, "dangerously ill". The second epidemic was noted early on as being of a different nature from the first and was frequently described as "fatal" and "violent" in many places, specifically in contrast to the first epidemic. New York City, for example, was severely affected. According to William Maclay, "many" in New York died every day from the disease during its prevalence in May. Abigail Adams wrote at this time that the flu had "in many places been very mortal, particularly upon long Island." In Newburyport, Massachusetts, it was reported at the end of May that "[t]he number of deaths, from influenza and other disorders in this part of the country, exceeds that of any other period now remembered." Indeed, in Boston, although most deaths occurred among the elderly, all age groups saw notable increases in mortality during the epidemic. Philadelphia, on the other hand, was apparently not much more severely affected than it had been in the fall. Symptoms of this influenza were similar to those of typical influenza . A cough was perhaps the notable symptom, affecting almost all afflicted with the disease. A fever was also common, in addition to chills and a universal lassitude. Pain in the head and the eyeballs were also reported. The disease during the first epidemic was described as being more "catarrhal" (i.e., coldlike) in nature, while during the second epidemic it was more "inflammatory". Pleurisy and "peripneumony" (pneumonia) were more common complications; inflammation of the heart, pericardium , and diaphragm were also observed in some victims. Uterine hemorrhages and spontaneous abortions were reported in some cases affecting pregnant women, the latter being a complication often associated with pandemic influenza. This epidemic occurred prior to the discovery of viruses , and so the exact cause of the disease could not have been known. Theories surrounding the cause, therefore, revolved more around whether the disease was contagious or whether atmospheric conditions were to blame. Some observers, such as Rush, considered the disease contagious; indeed, Rush and Irving considered contagion to be what distinguished the influenza from catarrh or a common cold . On the other hand, Webster attributed the prevalence of the disease to "insensible qualities of the atmosphere", based in part on his own experience with it, and considered the notion of its being spread mainly by infection as "very fallacious". In Webster's account of epidemic and pestilential diseases, he devotes considerable space to descriptions of weather conditions and other meteorological phenomena before and after epidemic periods. For 1789, he notes "an eruption of Vesuvius , just after a great earthquake at Iceland and in Europe"; a "warm summer" preceded the epidemic and a "mild winter" came after, before the 1790 epidemic. Richard H. Grove, of the Australian National University, Canberra , explored the potential role of the Great El Niño of the 1790s on global events, with reference to these aforementioned weather states in a 2006 study. He notes an association between this period and the incidence of influenza and concludes that "the very hot summers and mild winters which characterise El Niño conditions in much of North America appear to have encouraged the spread of epidemics in several different diseases, and not least in 1788–94." Indeed, El Niño events have been associated with the incidence of certain epidemic diseases, in particular those transmitted by mosquitoes. The relationship between the El Niño–Southern Oscillation and pandemic influenza has been explored as well, though studies have come to differing conclusions as to whether pandemics are associated with the El Niño or the La Niña phase of the cycle. Various "remedies" were relied upon to treat the disease. A medical student in Berkshire County, Massachusetts , describes the use of venesection , emetics , cathartics , antimonials and niter , and antiphlogistic drinks as common forms of treatment. To treat the cough, liquorice and paregoric elixir was frequently used. During convalescence, Peruvian bark was apparently "a most excellent medicine." Symptoms of this influenza were similar to those of typical influenza . A cough was perhaps the notable symptom, affecting almost all afflicted with the disease. A fever was also common, in addition to chills and a universal lassitude. Pain in the head and the eyeballs were also reported. The disease during the first epidemic was described as being more "catarrhal" (i.e., coldlike) in nature, while during the second epidemic it was more "inflammatory". Pleurisy and "peripneumony" (pneumonia) were more common complications; inflammation of the heart, pericardium , and diaphragm were also observed in some victims. Uterine hemorrhages and spontaneous abortions were reported in some cases affecting pregnant women, the latter being a complication often associated with pandemic influenza. This epidemic occurred prior to the discovery of viruses , and so the exact cause of the disease could not have been known. Theories surrounding the cause, therefore, revolved more around whether the disease was contagious or whether atmospheric conditions were to blame. Some observers, such as Rush, considered the disease contagious; indeed, Rush and Irving considered contagion to be what distinguished the influenza from catarrh or a common cold . On the other hand, Webster attributed the prevalence of the disease to "insensible qualities of the atmosphere", based in part on his own experience with it, and considered the notion of its being spread mainly by infection as "very fallacious". In Webster's account of epidemic and pestilential diseases, he devotes considerable space to descriptions of weather conditions and other meteorological phenomena before and after epidemic periods. For 1789, he notes "an eruption of Vesuvius , just after a great earthquake at Iceland and in Europe"; a "warm summer" preceded the epidemic and a "mild winter" came after, before the 1790 epidemic. Richard H. Grove, of the Australian National University, Canberra , explored the potential role of the Great El Niño of the 1790s on global events, with reference to these aforementioned weather states in a 2006 study. He notes an association between this period and the incidence of influenza and concludes that "the very hot summers and mild winters which characterise El Niño conditions in much of North America appear to have encouraged the spread of epidemics in several different diseases, and not least in 1788–94." Indeed, El Niño events have been associated with the incidence of certain epidemic diseases, in particular those transmitted by mosquitoes. The relationship between the El Niño–Southern Oscillation and pandemic influenza has been explored as well, though studies have come to differing conclusions as to whether pandemics are associated with the El Niño or the La Niña phase of the cycle. Various "remedies" were relied upon to treat the disease. A medical student in Berkshire County, Massachusetts , describes the use of venesection , emetics , cathartics , antimonials and niter , and antiphlogistic drinks as common forms of treatment. To treat the cough, liquorice and paregoric elixir was frequently used. During convalescence, Peruvian bark was apparently "a most excellent medicine."

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Pandemic influenza

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Biomedical Advanced Research and Development Authority

Gary Disbrow, Acting Director The Biomedical Advanced Research and Development Authority ( BARDA )' is a U.S. Department of Health and Human Services (HHS) office responsible for the procurement and development of medical countermeasures , principally against bioterrorism , including chemical, biological, radiological and nuclear (CBRN) threats , as well as pandemic influenza and emerging diseases. : 140 BARDA was established in 2006 through the Pandemic and All-Hazards Preparedness Act (PAHPA) and reports to the Office of the Assistant Secretary for Preparedness and Response (ASPR). The office manages Project BioShield , which funds the research, development and stockpiling of vaccines and treatments that the government could use during public health emergencies such as chemical, biological, radiological or nuclear (CBRN) attacks. : 140 In addition to preparing and maintaining bioterrorism responses and countermeasures, HHS , through the ASPR and BARDA, prepares and maintains an integrated system of medical countermeasures for both known or unknown, and re-emerging or novel types of public health emergencies . These include diagnostic tools, therapeutics, such as antibiotics and antivirals, and preventative measures, such as vaccines. BARDA is an established, official interface between the U.S. federal government and the biomedical industry. : 267 BARDA also participates in the governmental inter-agency Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), providing coordination across the US federal government in developing and deploying such countermeasures. : 267 BARDA works with the biomedical industry, using grants and other assistance, to promote advanced research, innovation and the development of medical devices, tests, vaccines and therapeutics. BARDA also procures and maintains stockpiles of materials, such as drugs, personal protective equipment (PPE) and vaccines, for the Strategic National Stockpile (SNS). BARDA was created and authorized by Title IV Sec 401 of the Pandemic and All-Hazards Preparedness Act (PAHPA) of 2006. PAHPA amended the Public Health Service Act by the addition of section 319L to that law. PAHPA provided new authorities for a number of programs to counter CBRN as well as epidemic, pandemic and emerging disease threats, established the position of Assistant Secretary for Preparedness and Response (ASPR) as well as BARDA reporting to the ASPR, and built on Project BioShield , previously created in 2004. PAHPA reauthorized the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, following the 2001 anthrax attacks ensuing the September 11, 2001 terrorist attacks on the United States. BARDA was reauthorized by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA) and again in the Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019 (PAHPAI). The inaugural director of BARDA, from its inception in 2006 through April 2008 was Carol D. Linden, who served both as the principal deputy director and acting director. From April 2008 through November 14, 2016, the director was Robin A. Robinson, formerly director of the BARDA Influenza and Emerging Diseases division. He was succeeded as director by Rick Bright from November 15, 2016 through April 20, 2020, when he was moved in what later became a whistleblower controversy during the COVID-19 pandemic in the United States (SARS-CoV-2). As of April 23, 2020, Gary Disbrow is the BARDA director, formerly director of the Medical Countermeasures program and director of the CBRN division at BARDA. All early BARDA directors also concurrently served as Deputy Assistant Secretary for Preparedness and Response . BARDA's 2011–2016 Strategic plan described its composition as the Office of the Director plus seven functional divisions: Chemical, Biological, Radiological and Nuclear Countermeasures (CBRN) Countermeasures Clinical Studies Influenza Manufacturing Facilities and Engineering Modeling Regulatory and Quality Affairs Strategic Science and Technology In June 2018, BARDA announced a new initiative, its Division of Research Innovation and Ventures (DRIVe). DRIVe is a business accelerator to fund and support the development of a portfolio of healthcare products.BARDA was created and authorized by Title IV Sec 401 of the Pandemic and All-Hazards Preparedness Act (PAHPA) of 2006. PAHPA amended the Public Health Service Act by the addition of section 319L to that law. PAHPA provided new authorities for a number of programs to counter CBRN as well as epidemic, pandemic and emerging disease threats, established the position of Assistant Secretary for Preparedness and Response (ASPR) as well as BARDA reporting to the ASPR, and built on Project BioShield , previously created in 2004. PAHPA reauthorized the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, following the 2001 anthrax attacks ensuing the September 11, 2001 terrorist attacks on the United States. BARDA was reauthorized by the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA) and again in the Pandemic and All-Hazards Preparedness and Advancing Innovation Act of 2019 (PAHPAI).The inaugural director of BARDA, from its inception in 2006 through April 2008 was Carol D. Linden, who served both as the principal deputy director and acting director. From April 2008 through November 14, 2016, the director was Robin A. Robinson, formerly director of the BARDA Influenza and Emerging Diseases division. He was succeeded as director by Rick Bright from November 15, 2016 through April 20, 2020, when he was moved in what later became a whistleblower controversy during the COVID-19 pandemic in the United States (SARS-CoV-2). As of April 23, 2020, Gary Disbrow is the BARDA director, formerly director of the Medical Countermeasures program and director of the CBRN division at BARDA. All early BARDA directors also concurrently served as Deputy Assistant Secretary for Preparedness and Response .BARDA's 2011–2016 Strategic plan described its composition as the Office of the Director plus seven functional divisions: Chemical, Biological, Radiological and Nuclear Countermeasures (CBRN) Countermeasures Clinical Studies Influenza Manufacturing Facilities and Engineering Modeling Regulatory and Quality Affairs Strategic Science and Technology In June 2018, BARDA announced a new initiative, its Division of Research Innovation and Ventures (DRIVe). DRIVe is a business accelerator to fund and support the development of a portfolio of healthcare products.BARDA plays a unique and unusual role within the structure of the US Federal Government, assisting in getting drugs, deemed essential during public health emergencies including attacks compromising US national security, to market. Such assistance ranges from direct funding, procuring and stockpiling medical countermeasures (MCM's), to helping obtain US FDA approvals, including Emergency Use Authorization (EUA) if needed. By the rare nature of such public health emergencies, the required therapies or countermeasures, while critical during the emergency, may not constitute a financially viable or profitable investment, for sufficiently large pharmaceutical companies. Such gaps in the US government medical countermeasures infrastructure have been described as "bridging the valley of death". In this respect, BARDA provides services similar to those offered by venture capitalists or business accelerators in private industry, although BARDA takes no financial stake in the final product once approved by the FDA. BARDA acts in concert with the PHEMCE . These activities (see below) include: Setting Requirements for Medical Countermeasures (MCM's) Funding Advanced Research and Development (ADR) for CBRN and pandemic MCM's Administration of National Biodefense Fund(s) Promoting Innovation in Development and Manufacturing Acquiring and Maintaining MCM StockpilesDuring public health emergencies, BARDA's budget may be increased by additional congressional appropriations. In FY 2020, the annual budget of BARDA was approximately $1.6 billion depending on the precise allocation of costs, including the costs of projects overseen or managed by BARDA on behalf of the ASPR. The proposed budget in FY 2020, not reflecting any additional congressional appropriations due to the COVID-19 crisis, was an increase from $1.27 billion in FY 2019, and $1.02 billion in FY 2018. This figure included $512 million in medical countermeasures including $192 million for combating antibiotic-resistant bacteria and $260 million USD for advanced research and development (ARD).Research and development Medical countermeasures Vaccines Antimicrobial drugs Therapeutic products Diagnostics Non-pharmaceutical medical supplies Stockpiling programs (see below) Project BioShield Pandemic Influenza Emergency Supplemental Fund Strategic National Stockpile Antibiotics Vaccines Anthrax vaccine Antidotes Medical equipment and supplies Manufacturing infrastructure Medical countermeasures Vaccines Antimicrobial drugs Therapeutic products Diagnostics Non-pharmaceutical medical supplies Vaccines Antimicrobial drugs Therapeutic products Diagnostics Non-pharmaceutical medical supplies Project BioShield Pandemic Influenza Emergency Supplemental Fund Strategic National Stockpile Antibiotics Vaccines Anthrax vaccine Antidotes Medical equipment and supplies Antibiotics Vaccines Anthrax vaccine Antidotes Medical equipment and suppliesBARDA sets the requirements for medical countermeasures in order to reduce the threats of public health emergencies such as pandemic influenza, CBRN threats, and emerging diseases. The requirements formalize the minimum standards private industry needs to use in order to produce medical countermeasures acceptable to BARDA. Stakeholders across the federal government and the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) specify requirements. Once established, these requirements drive BARDA's advanced research and development, as well as acquisition. Requirements are created consistent with the planning and prioritization expressed in the HHS PHEMCE Implementation Plan for CBRN Threats. Pandemic Influenza requirements are defined by strategic objectives established in the "National Strategy for Pandemic Influenza" and the "HHS Pandemic Influenza Plan". Stakeholders across the federal government and the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) specify requirements. Once established, these requirements drive BARDA's advanced research and development, as well as acquisition. Requirements are created consistent with the planning and prioritization expressed in the HHS PHEMCE Implementation Plan for CBRN Threats. Pandemic Influenza requirements are defined by strategic objectives established in the "National Strategy for Pandemic Influenza" and the "HHS Pandemic Influenza Plan". One of BARDA's major objectives is the creation of a robust and dynamic pipeline of medical countermeasures through advanced research and development (ARD). Its goal is to provide multiple product candidates in each program to both account for attrition in medical countermeasure deployment and to establish multi-product/multi-manufacturer portfolios for sustainability and redundancy. BARDA medical countermeasures include vaccines, antimicrobial drugs, therapeutic products, diagnostics and non-pharmaceutical medical supplies, as well as devices for public health medical emergencies including chemical, biological, radiological, and nuclear threats (CBRN), pandemic influenza (PI) and emerging infectious diseases (EID). One of BARDA's key activities includes the Influenza and Emerging Infectious Diseases Division. This program aims to support the advanced development of vaccines, therapeutic and diagnostic medical countermeasures that address emerging infectious disease threats. Nerve agents and other chemical weapons are a priority for fighting CBRN threats. VX gas , which was the nerve agent that reportedly killed the half-brother of North Korean leader Kim Jong-un , Provides an example. BARDA also stockpiles an anti-seizure medication, midazolam , developed by Meridian Medical Technologies , to be made available in an autoinjector to treat the effects of nerve agents on the neurological system. Research into substitute medical countermeasures (MCM) against nerve agents conducted by BARDA has shown the utility of current atropine solutions used in limited quantities in the treatment of cholinergic pathologies, to promote dilation of the eye, or organophosphate poisoning. Noting the lack of sufficient stocks in the case of mass-casualty situations, citing the 1995 Toyko subway sarin attack , the study proposed alternate routes of administration (ROI) for atropine. The bioavailability of atropine via alternate ROIs was proven to be effective, though consideration was placed on expansion of atropine stockpiles and the dispersion of MCMs to local entities. In October 2017 BARDA entered a nine-month $12-million contract with the San Francisco-based biopharmaceutical company Achaogen, sponsoring late-stage development of C-scape, an antibiotic used against resistant bacteria and a potential treatment against weaponized strains of bacteria. In April 2019, Achaogen declared bankrupt. One of BARDA's major objectives is the creation of a robust and dynamic pipeline of medical countermeasures through advanced research and development (ARD). Its goal is to provide multiple product candidates in each program to both account for attrition in medical countermeasure deployment and to establish multi-product/multi-manufacturer portfolios for sustainability and redundancy. BARDA medical countermeasures include vaccines, antimicrobial drugs, therapeutic products, diagnostics and non-pharmaceutical medical supplies, as well as devices for public health medical emergencies including chemical, biological, radiological, and nuclear threats (CBRN), pandemic influenza (PI) and emerging infectious diseases (EID). One of BARDA's key activities includes the Influenza and Emerging Infectious Diseases Division. This program aims to support the advanced development of vaccines, therapeutic and diagnostic medical countermeasures that address emerging infectious disease threats.Nerve agents and other chemical weapons are a priority for fighting CBRN threats. VX gas , which was the nerve agent that reportedly killed the half-brother of North Korean leader Kim Jong-un , Provides an example. BARDA also stockpiles an anti-seizure medication, midazolam , developed by Meridian Medical Technologies , to be made available in an autoinjector to treat the effects of nerve agents on the neurological system. Research into substitute medical countermeasures (MCM) against nerve agents conducted by BARDA has shown the utility of current atropine solutions used in limited quantities in the treatment of cholinergic pathologies, to promote dilation of the eye, or organophosphate poisoning. Noting the lack of sufficient stocks in the case of mass-casualty situations, citing the 1995 Toyko subway sarin attack , the study proposed alternate routes of administration (ROI) for atropine. The bioavailability of atropine via alternate ROIs was proven to be effective, though consideration was placed on expansion of atropine stockpiles and the dispersion of MCMs to local entities. In October 2017 BARDA entered a nine-month $12-million contract with the San Francisco-based biopharmaceutical company Achaogen, sponsoring late-stage development of C-scape, an antibiotic used against resistant bacteria and a potential treatment against weaponized strains of bacteria. In April 2019, Achaogen declared bankrupt. The Pandemic and All-Hazards Preparedness Act (PAHPA) established BARDA as the focal point within HHS for the advanced development and acquisition of medical countermeasures to protect the American civilian population against Chemical, Biological, Radiological, and Nuclear (CBRN) and naturally occurring threats to public health. BARDA's stockpiling efforts are focused on building reserves of critical countermeasures as they emerge from Advanced Development. Stockpiling contributes to preparedness in two ways: Stockpiled medical countermeasures directly support readiness, as the stockpiled products can help to mitigate the effects of an event or outbreak. Establishment of the stockpile helps to ready suppliers to meet the increased demands that an event will bring about, becoming practiced in the production and delivery of products. BARDA's acquisitions for the stockpile are not one-time events, complete upon the approval/licensure of a product. Rather, programs are structured to include incremental milestone acquisitions during late stage development, to make available products still in development that may increase preparedness in an event, pending Emergency Use Authorization. Furthermore, we aim to establish stockpiling milestones to address long-term commitments post-licensure. In FY 2004, the US Congress appropriated $5.6 billion USD to the Project BioShield Special Reserve Fund (SRF) to support the Project BioShield goal of acquiring CBRN medical countermeasures over a 10-year period. BARDA used these funds to support acquisition programs for the procurement of medical countermeasures against high priority CBRN threats. The agency gives funds to pharmaceutical companies to develop countermeasures. As of January 2020, BARDA had helped obtain FDA approval for at least 50 products. Using funds from the Pandemic Influenza Emergency Supplemental Fund, BARDA is leading the nation toward the vaccine and antiviral stockpile goals for preparedness for pandemic influenza. In December 2019, BARDA awarded a $226 million USD six-year contract to Sanofi Pasteur , a global pharmaceutical company with U.S. headquarters in Bridgewater, New Jersey, to increase production capacity for an influenza vaccine. In September 2019, a US presidential executive order required the US government to modernize influenza vaccines and technologies in order to improve national health security. The Public Health Security and Bioterrorism Preparedness Act of 2002 directed the Secretary of Health and Human Services to develop and maintain a Strategic National Stockpile (SNS). The mission of the SNS is to provide for the emergency health security of the United States in the event of a terrorist attack or any other public health emergency. The SNS is the largest US national supply of pharmaceuticals and medical supplies for use in a small outbreak to a large-scale, multiple-threat emergency. When state, local, tribal, and/or territorial responders request federal assistance to support their response efforts, the stockpile is used to ensure that supplies are available when and where needed. The SNS is Intended to contains enough vaccines, antimicrobial drugs, therapeutic products, and non-pharmaceutical medical supplies in the wake of any public health emergency including terrorist attacks whether chemical, biological, radiological, and/or nuclear, as well as pandemic influenza and emerging infectious diseases. Emergent BioSolutions manufactures the only FDA licensed vaccine against anthrax disease, called BioThrax , which is recommended by the CDC as a post-exposure prophylactic for anthrax infection. As part of a $450 million contract with BARDA for the SNS, Emergent also developed the only FDA-licensed botulinum antitoxin, Heptavalent Botulism Antitoxin (BAT) for treating naturally occurring botulism. [v] Canada also approved BAT. The US federal government approved a plan against CBRN threats after the 2001 anthrax letters attack, at the time the worst biological attack in United States history. BARDA also invested in the late stage development of a product called NuThrax developed by Emergent Biosolutions, which makes the other anthrax vaccine, BioThrax. According to Homeland Preparedness News , NuThrax will be able to provide immunity to anthrax after two doses, versus the three doses under the currently stockpiled vaccine (BioThrax). In FY 2004, the US Congress appropriated $5.6 billion USD to the Project BioShield Special Reserve Fund (SRF) to support the Project BioShield goal of acquiring CBRN medical countermeasures over a 10-year period. BARDA used these funds to support acquisition programs for the procurement of medical countermeasures against high priority CBRN threats. The agency gives funds to pharmaceutical companies to develop countermeasures. As of January 2020, BARDA had helped obtain FDA approval for at least 50 products. Using funds from the Pandemic Influenza Emergency Supplemental Fund, BARDA is leading the nation toward the vaccine and antiviral stockpile goals for preparedness for pandemic influenza. In December 2019, BARDA awarded a $226 million USD six-year contract to Sanofi Pasteur , a global pharmaceutical company with U.S. headquarters in Bridgewater, New Jersey, to increase production capacity for an influenza vaccine. In September 2019, a US presidential executive order required the US government to modernize influenza vaccines and technologies in order to improve national health security. The Public Health Security and Bioterrorism Preparedness Act of 2002 directed the Secretary of Health and Human Services to develop and maintain a Strategic National Stockpile (SNS). The mission of the SNS is to provide for the emergency health security of the United States in the event of a terrorist attack or any other public health emergency. The SNS is the largest US national supply of pharmaceuticals and medical supplies for use in a small outbreak to a large-scale, multiple-threat emergency. When state, local, tribal, and/or territorial responders request federal assistance to support their response efforts, the stockpile is used to ensure that supplies are available when and where needed. The SNS is Intended to contains enough vaccines, antimicrobial drugs, therapeutic products, and non-pharmaceutical medical supplies in the wake of any public health emergency including terrorist attacks whether chemical, biological, radiological, and/or nuclear, as well as pandemic influenza and emerging infectious diseases. Emergent BioSolutions manufactures the only FDA licensed vaccine against anthrax disease, called BioThrax , which is recommended by the CDC as a post-exposure prophylactic for anthrax infection. As part of a $450 million contract with BARDA for the SNS, Emergent also developed the only FDA-licensed botulinum antitoxin, Heptavalent Botulism Antitoxin (BAT) for treating naturally occurring botulism. [v] Canada also approved BAT. The US federal government approved a plan against CBRN threats after the 2001 anthrax letters attack, at the time the worst biological attack in United States history. BARDA also invested in the late stage development of a product called NuThrax developed by Emergent Biosolutions, which makes the other anthrax vaccine, BioThrax. According to Homeland Preparedness News , NuThrax will be able to provide immunity to anthrax after two doses, versus the three doses under the currently stockpiled vaccine (BioThrax). Ensuring the availability of medical countermeasures for public health emergencies is central to BARDA's mission. This includes ensuring that manufacturing infrastructure is sufficient to support the production of required products, in a manner that is timely, reliable and cost effective. BARDA has taken multiple approaches to bringing online the necessary infrastructure for medical countermeasure manufacturing; it supports the construction of new facilities as well as retrofitting existing facilities for maximal capacity and flexibility. It has also explored the use of multi-product manufacturing facilities to provide flexibility and surge capacity and enable rapidly providing countermeasures in the dosage forms required for use in the field. BARDa has also established a network of formulation/fill-finish manufacturers for emergency production and distribution. BARDA has also explored the creation of centers of excellence for the development and production of non-commercial products with assistance from industry partners. PAHPA charges BARDA to support innovation to reduce the time and cost of medical countermeasures and product advanced research and development. This was to be accomplished through development of technologies that assist the advanced development of countermeasures, investment in research tools and technologies, and research to promote strategic initiatives including rapid diagnostics, broad spectrum antimicrobials, and vaccine manufacturing technologies. PAHPAI provided further authorities for BARDA to promote innovation through industry assistance and partnerships. BARDA has taken this innovation mandate as an opportunity to work with its partners (including NIH, DoD, CDC, industry, and academia) to create new ways to "make medical countermeasure better." Examples of this approach to innovation could include the development of animal models to support efficacy testing, immune modulation and other broad-spectrum approaches, immunity assessment, and analytical (potency) assays. A cited example of BARDA's approach to innovation from the Pandemic Influenza program is BARDA's "Mix and Match" study, assessing various combinations of antigens and adjuvants to obtain a more robust immune response. BARDA has stated plans to support similar initiatives, leveraging technology platforms and products from multiple companies. For example, PAHPA provided an "antitrust" authority that BARDA has used to facilitate cooperation between companies for whom such cooperation would otherwise be difficult to accomplish. Fujifilm Corporation announced in April 2017 that it would invest $130 million to increase production capacity for its BioCDMO division. The division "focuses on contract development & manufacturing for biologics." Fujifilm Diosynth Biotechnologies, with help from a BARDA grant, invested around $93 million to build a production facility in the US state of Texas. The facility would include "mammalian cell culture bioreactors" and was planned to open operations at the start of 2018. In April 2017, Switzerland-based Basilea Pharmaceutica and the Food and Drug Administration reached an agreement regarding two phase 3 clinical studies of an antibiotic developed by Basilea, ceftobiprole . The two clinical studies would examine ceftobiprole for the treatment of " Staphylococcus aureus bacteremia (bloodstream infections) and acute bacterial skin and skin structure infections." Basilea signed a contract with BARDA, which it entered into in 2016 for the clinical phase 3 development of the antibiotic. BARDA provided initial funding of $20 million but could provide up to $100 million over a period of 4–5 years. In 2017, BARDA signed a three-year $8.1 million contract with InBios International, Inc. of Seattle, Washington to develop a " point-of-care diagnostic test that may be able to determine within 15 minutes whether a patient has been infected with the bacterium that causes anthrax ." In September 2017, BARDA awarded Velico Medical $15.5 million for development of a technology that uses spray drying of human plasma for transfusions. The current industry standard is to freeze plasma. Frozen plasma can take 40 or more minutes to defrost and deliver. According to Fierce Biotech, "Velico has Spray Dried Plasma technology (SpDPTM) that enables the storage of blood as dry powder, rather than the typical freezing, for subsequent rehydration. It's expected to be useful in hospital emergency rooms , operating suites and intensive care units --as well as in a military or field hospital setting." In July 2005, at the hearings before the Committee on Health, Education, Labor, and Pensions, the first CEO and Director of the center, Tara O'Toole , MD, MPH, has pointed to center's role as the "BioDARPA" (i.e. "biomedical DARPA "). Since the 2001 anthrax attacks in the United States, BARDA has supported the research and development of diagnostics, therapeutics and vaccines for anthrax . Therapeutics include the antibiotics XERAVA Of Tetraphase Pharmaceuticals , ZEMDRI of Achaogen (rights ex-Greater China bought by Cipla USA) Gepotidacin of GlaxoSmithKline and SPR994 of Spero Therapeutics . In July 2018, Spero was jointly awarded up to USD $54 million by BARDA and the Defense Threat Reduction Agency (DTRA), in support of SPR994 development. SPR994 also has application to the treatment of multi-drug resistant (MDR) bacteria. BARDA also supported the development of the antitoxins Anthrasil of Cangene (March 2015 FDA approval) and Anthim of Elusys Therapeutics (March 2016 FDA approval). Anthrax vaccines whose development was supported by BARDA include BioThrax (AVA), AV7909 of Emergent BioSolutions Px563L of Pfenex and NasoShield of Altimmune . Botulism is caused by the botulinum toxin , one of the deadliest known toxins. While the bacteria that cause botulism occur naturally, botulism outbreaks are considered rare and unlikely by the US CDC , except as the result of a bioterrorism attack. BARDA maintains a supply of botulism antitoxins through the Strategic National Stockpile (SNS). As of June, seven companies had been chosen for funding from Operation Warp Speed to expedite development and preparation for manufacturing their respective vaccine candidates: Johnson & Johnson ( Janssen Pharmaceutical ), AstraZeneca - University of Oxford , Pfizer -BioNTech, Moderna , Merck , Vaxart , and Inovio . Funding from BARDA totaled more than $2 billion by the end of June, with the largest awards of $1.2 billion given to AstraZeneca and $483 million to Moderna. In June 2020, BARDA and the U.S. Department of Defenses signed a $143 million contract with SiO2 Materials Science to ramp up production of vials and syringes used for COVID drugs and vaccines. After the 2014 West Africa Ebola virus epidemic (followed by the Kivu Ebola epidemic starting in 2018), BARDA supported the development of the first Ebola vaccine, ERVEBO , by BioProtection Systems , a subsidiary of NewLink Genetics Inc. (now Lumos Pharma ). The vaccine was announced by the ASPR on December 19, 2019; ERVEBO , a vaccine for the Zaire ebola virus was licensed from NewLink Genetics in 2014 and produced and taken to market by Merck . It was successfully used in the 2018 Ebola virus epidemic in the Democratic Republic of the Congo (DRC). Smallpox is a highly contagious, potentially fatal disease caused by the Variola virus . While the US discontinued immunization in 1972, and it was declared eradicated by the World Health Organization (WHO) in 1980 (the last known naturally occurring case was seen in 1977, in Somalia), it is still considered a potent bioterrorism threat. BARDA began stockpiling smallpox vaccines in 2010. By 2018, BARDA had procured millions of doses of TPOXX , of SIGA Technologies , by then the first (and only) FDA-approved antiviral smallpox drug therapy, for the SNS. In 2019, BARDA announced a partnership with BioFactura to develop a second therapeutic, a monoclonal antibody smallpox treatment. As of early 2020, there were no publicly acknowledged BARDA biomedical collaborations (diagnostics, therapies or vaccines) for the Zika virus . However BARDA has an announced (general) four-part Zika strategy Prevention (vaccines) Detection (diagnostics) Ensuring a safe blood supply (screening) National Countermeasure Response Activation (developer assistance)Since the 2001 anthrax attacks in the United States, BARDA has supported the research and development of diagnostics, therapeutics and vaccines for anthrax . Therapeutics include the antibiotics XERAVA Of Tetraphase Pharmaceuticals , ZEMDRI of Achaogen (rights ex-Greater China bought by Cipla USA) Gepotidacin of GlaxoSmithKline and SPR994 of Spero Therapeutics . In July 2018, Spero was jointly awarded up to USD $54 million by BARDA and the Defense Threat Reduction Agency (DTRA), in support of SPR994 development. SPR994 also has application to the treatment of multi-drug resistant (MDR) bacteria. BARDA also supported the development of the antitoxins Anthrasil of Cangene (March 2015 FDA approval) and Anthim of Elusys Therapeutics (March 2016 FDA approval). Anthrax vaccines whose development was supported by BARDA include BioThrax (AVA), AV7909 of Emergent BioSolutions Px563L of Pfenex and NasoShield of Altimmune .Botulism is caused by the botulinum toxin , one of the deadliest known toxins. While the bacteria that cause botulism occur naturally, botulism outbreaks are considered rare and unlikely by the US CDC , except as the result of a bioterrorism attack. BARDA maintains a supply of botulism antitoxins through the Strategic National Stockpile (SNS).As of June, seven companies had been chosen for funding from Operation Warp Speed to expedite development and preparation for manufacturing their respective vaccine candidates: Johnson & Johnson ( Janssen Pharmaceutical ), AstraZeneca - University of Oxford , Pfizer -BioNTech, Moderna , Merck , Vaxart , and Inovio . Funding from BARDA totaled more than $2 billion by the end of June, with the largest awards of $1.2 billion given to AstraZeneca and $483 million to Moderna. In June 2020, BARDA and the U.S. Department of Defenses signed a $143 million contract with SiO2 Materials Science to ramp up production of vials and syringes used for COVID drugs and vaccines. After the 2014 West Africa Ebola virus epidemic (followed by the Kivu Ebola epidemic starting in 2018), BARDA supported the development of the first Ebola vaccine, ERVEBO , by BioProtection Systems , a subsidiary of NewLink Genetics Inc. (now Lumos Pharma ). The vaccine was announced by the ASPR on December 19, 2019; ERVEBO , a vaccine for the Zaire ebola virus was licensed from NewLink Genetics in 2014 and produced and taken to market by Merck . It was successfully used in the 2018 Ebola virus epidemic in the Democratic Republic of the Congo (DRC).Smallpox is a highly contagious, potentially fatal disease caused by the Variola virus . While the US discontinued immunization in 1972, and it was declared eradicated by the World Health Organization (WHO) in 1980 (the last known naturally occurring case was seen in 1977, in Somalia), it is still considered a potent bioterrorism threat. BARDA began stockpiling smallpox vaccines in 2010. By 2018, BARDA had procured millions of doses of TPOXX , of SIGA Technologies , by then the first (and only) FDA-approved antiviral smallpox drug therapy, for the SNS. In 2019, BARDA announced a partnership with BioFactura to develop a second therapeutic, a monoclonal antibody smallpox treatment. As of early 2020, there were no publicly acknowledged BARDA biomedical collaborations (diagnostics, therapies or vaccines) for the Zika virus . However BARDA has an announced (general) four-part Zika strategy Prevention (vaccines) Detection (diagnostics) Ensuring a safe blood supply (screening) National Countermeasure Response Activation (developer assistance)(such as VX) Table source: The Department of Defense (DoD) and HHS each identify medical countermeasure requirements to address their different missions and focus. DoD's focus is on protecting the armed forces prior to exposure, whereas HHS's focus is on response to threats to the civilian population after exposure in a CBRN event. However, there are areas of common requirements or interest where medical countermeasure candidates, resources and information can be appropriately shared to maximize opportunities for success in the development of medical countermeasures for the highest priority threats. BARDA, in partnership with other HHS and DoD partners, is leading an Integrated National Biodefense Medical Countermeasure Portfolio to leverage resources and programs across the agencies that develop and acquire CBRN medical countermeasures to more effectively address the broad range of common threats and requirements. Members of this Integrated Portfolio include BARDA, biodefense programs in the National Institute of Allergy and Infectious Diseases (NIAID), which also oversees all biodefense activities across the other Institutes of the National Institutes of Health (NIH), and multiple elements of the DoD Chemical and Biological Defense Program.On April 20, 2020, during the COVID-19 pandemic in the United States , in an action that led to the filing of a US whistleblower complaint and testimony before the US House of Representatives, Rick Bright was asked to step down as Director of BARDA. Bright claimed he had been removed from his post because he had insisted that "the billions of dollars allocated by Congress to address the COVID-19 pandemic" be invested "into safe and scientifically vetted solutions, and not in drugs, vaccines and other technologies that lack scientific merit." Bright was reassigned to the National Institutes of Health (NIH). The Assistant Secretary for Preparedness and Response (ASPR) at the time, who was implicated in the complaint, was Robert Kadlec . On January 27, 2021, the U.S. Office of Special Counsel transmitted an investigative report to President Biden confirming whistleblower allegations that ASPR "misappropriated millions of dollars that Congress appropriated for [BARDA] to respond to public health emergencies like outbreaks of Ebola, Zika, and—now—COVID-19." The investigation by the HHS Office of Inspector General (OIG) substantiated whistleblower claims that "ASPR did not always comply with Federal fiscal law when managing BARDA appropriations." In his transmittal letter, Special Counsel Henry Kerner wrote the President that he was "deeply concerned about ASPR's apparent misuse of millions of dollars in funding meant for public health emergencies like the one our country is currently facing with the COVID-19 pandemic. Equally concerning is how widespread and well-known this practice appeared to be for nearly a decade."

Wiki

Pandemic influenza

https://api.wikimedia.org/core/v1/wikipedia/en/page/Influenza_A_virus_subtype_H7N9/html

Influenza A virus subtype H7N9

Influenza A virus subtype H7N9 (A/H7N9) is a bird flu strain of the species Influenza virus A ( avian influenza virus or bird flu virus). Avian influenza A H7 viruses normally circulate amongst avian populations with some variants known to occasionally infect humans. An H7N9 virus was first reported to have infected humans in March 2013, in China. Cases continued to be reported throughout April and then dropped to only a few cases during the summer months. At the closing of the year, 144 cases had been reported of which 46 had died. It is known that influenza tends to strike during the winter months, and the second wave, which began in October, was fanned by a surge in poultry production timed for Lunar New Year feasts that began at the end of January. January 2014 brought a spike in reports of illness with 96 confirmed reports of disease and 19 deaths. As of April 11, 2014, the outbreak's overall total was 419, including 7 in Hong Kong, and the unofficial number of deaths was 127. A 5th epidemic of the H7N9 virus began in October 2016 in China. The epidemic is the largest since the first epidemic in 2013 and accounts for about one-third of human cases ever reported. The cumulative total of laboratory-confirmed cases since the first epidemic is 1,223. About 40 percent have died. The CDC estimates that the H7N9 virus has the greatest potential compared with other influenza A viruses to cause a pandemic, although the risk is low because, like other type A viruses, it is not easily transmitted between people in its current form. The World Health Organization (WHO) has identified H7N9 as "...an unusually dangerous virus for humans." Most of the cases resulted in severe respiratory illness, with a mortality rate of roughly 30 percent. Researchers have commented on the unusual prevalence of older males among H7N9-infected patients. While several environmental, behavioral, and biological explanations for this pattern have been proposed, the reason remains unknown. It has been established that many of the human cases of H7N9 appear to have a link to live bird markets. As of January 2014, there has been no evidence of sustained human-to-human transmission; however, a study group headed by one of the world's leading experts on avian flu reported that several instances of human-to-human infection are suspected. The H7N9 virus does not kill poultry, which makes surveillance much more difficult. [ citation needed ] Chinese scientists announced the development of a vaccine on October 26, 2013, but said that H7N9 had not spread far enough to merit widespread vaccination. Research regarding background and transmission is ongoing. Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemagglutinin (HA) and neuraminidase (NA). The avian influenza A(H7N9) virus designation of H7N9 identifies it as having HA of the H7 subtype and NA of the N9 subtype. Avian influenza A H7 viruses are a group of influenza viruses that normally circulate among birds. H7 influenza infections in humans are uncommon, but have been confirmed worldwide in people who have direct contact with infected birds. Most infections have been mild involving only conjunctivitis and mild upper respiratory symptoms. The avian influenza A(H7N9) virus is a subgroup among this larger group of H7 viruses. Although some H7 viruses (e.g. H7N2 , H7N3 and H7N7 ) have occasionally been found to infect humans, H7N9 has previously been isolated only in birds, with outbreaks reported in the Netherlands , Japan , and the United States . Until the 2013 outbreak in China , no human infections with H7N9 viruses had ever been reported. Genetic characterisation of avian influenza A(H7N9) shows that the H7N9 virus that infects human beings resulted from the recombination of genes between several parent viruses noted in poultry and wild birds in Asia. It is most closely related to sequences found in samples from ducks in Zhejiang province in 2011. Evidence so far suggests that the new H7N9 virus might have evolved from at least four origins. It is hypothesized that the gene that codes for HA has its origin in ducks and the gene that codes for NA has its origin with ducks and probably also wild birds. Six internal genes originated with at least two H9N2 chicken viruses. The HA genes were circulating in the East Asian flyway in both wild birds and ducks, while the NA genes were introduced from European lineages and transferred to ducks in China by wild birds through migration along the East Asian flyway. Dr. Keiji Fukuda , WHO's assistant director-general for health security and environment, remarked at a Toronto interview that "I think we are genuinely in new territory here in which the situation of having something that is low path in birds (yet) appears to be so pathogenic in people... And then to have those genetic changes ... I simply don't know what that combination is going to lead to." "Almost everything you can imagine is possible. And then what's likely to happen are the things which you can't imagine," he also remarked. According to the deputy director of CDC's influenza division, the genetic makeup of H7N9 is "disturbingly different" from that of the H5N1 virus that has infected more than 600 people over the past 10 years and killed more than half of them. "The thing that's different between them is the H5 virus still maintains a lot of the avian or bird flu characteristics, whereas this H7N9 shows some adaptation to mammals. And that's what makes it different and concerning for us. It still has a ways to go before it becomes like a human virus, but the fact is, it's somewhere in that middle ground between purely avian and purely human." In August 2013, it was announced that scientists plan to create mutant forms of the virus so they can gauge the risk of it becoming a lethal human pandemic. The genetic modification work will result in highly transmissible and deadly forms of H7N9, and is being carried out in several high security laboratories around the world. Most human infections with avian influenza viruses, including Asian H7N9 virus, occur after exposure to infected poultry or contaminated environments. Asian H7N9 viruses continue to circulate in poultry in China. Most reported patients with H7N9 virus infection have had severe respiratory illness (e.g., pneumonia). Rare instances of limited person-to-person spread of this virus have been identified in China, but there is no evidence of sustained person-to-person spread. Some human infections with Asian H7N9 virus have been reported outside of mainland China, Hong Kong or Macao but all of these infections have occurred among people who had traveled to China before becoming ill. Asian H7N9 viruses have not been detected in people or birds in the United States. Most human infections with avian influenza viruses, including Asian H7N9 virus, occur after exposure to infected poultry or contaminated environments. Asian H7N9 viruses continue to circulate in poultry in China. Most reported patients with H7N9 virus infection have had severe respiratory illness (e.g., pneumonia). Rare instances of limited person-to-person spread of this virus have been identified in China, but there is no evidence of sustained person-to-person spread. Some human infections with Asian H7N9 virus have been reported outside of mainland China, Hong Kong or Macao but all of these infections have occurred among people who had traveled to China before becoming ill. Asian H7N9 viruses have not been detected in people or birds in the United States. On March 31, 2013, the Centre for Health Protection (CHP) of the Department of Health of Hong Kong and the Chinese National Health and Family Planning Commission notified the World Health Organization of three confirmed human cases of influenza A (H7N9) in Shanghai and Anhui (illness onset between February 19 and March 15, 2013). On April 2, the CHP confirmed four more cases in Jiangsu province , all considered in critical condition in hospitals in Nanjing , Suzhou , and Wuxi . In a statement, the CHP said that no epidemiologic links had been found between the four patients and so far no other H7N9 infections have been identified in 167 of their close contacts. The first reported death associated with H7N9 was an 87-year-old man who died on March 4. A second man, aged 27, died on March 10. On April 3, Chinese authorities reported another death, bringing the number to three. On April 4, the number of reported cases was 14, with 5 deaths. The two victims were a 48-year-old man and a 52-year-old woman, both from Shanghai. On April 5, a farmer, aged 64, living in Huzhou ( Zhejiang province), died, raising the death toll to 6. On April 6, the Chinese Ministry of Health reported 18 positive cases, death toll still at 6. Two days later, positive cases rose to 24 and one death case from Shanghai brought the death toll to 7. On April 9, the Chinese National Health and Family Planning Commission announced "an additional three laboratory-confirmed cases of human infection with influenza A(H7N9) virus." The new patients "are two patients from Jiangsu – an 85-year-old man who became ill on 28 March 2013" and a "25-year-old pregnant woman who became ill on 30 March 2013" and "a 64-year-old man from Shanghai who became ill on 1 April 2013, and died on 7 April 2013". As of April 9, a "total of 24 cases have been laboratory confirmed with influenza A(H7N9) virus in China, including seven deaths, 14 severe cases and three mild cases." In Jiangsu, more than "600 close contacts of the confirmed cases are being closely monitored." In an update on April 11, Xinhua reported 38 identified cases and 10 deaths. According to the WHO , of the 28 patients who had survived their infections, 19 illnesses were severe and 9 were mild. The WHO said they were monitoring 760 close contacts and so far had no evidence of ongoing human-to-human transmission. On April 13, a seven-year-old girl from Beijing was the first confirmed case of H7N9 bird flu outside eastern China. On April 14, Xinhua Chinese state media reported two human cases in central Henan just west of the area where the disease had been centered. Totals included 61 infected and 13 dead. On April 14, Chinese officials also reported the first asymptomatic case in Beijing. A health department notice suggested that a 4-year-old boy had no clinical symptoms and was tested during surveillance of high-risk groups. On April 17, a total of 82 cases had been confirmed, with 17 deaths. On April 18, China reported 87 confirmed cases. On April 20, there were 96 confirmed cases, of which 18 were fatal. On the next day, confirmed cases rose to 102 and fatal cases to 20. On April 22, there were 104 cases with 21 deaths. On April 23, 3 more cases were reported in an update from the WHO . All of the newly reported cases were in older men from eastern China. Two cases came from the Zhejiang province and the third was from the Anhui province. Total cases count reached 108 with 22 deaths. On April 24, a case was confirmed by the Taiwanese Government, marking the first case outside of Mainland China. On April 25, the National Health and Family Planning Commission said that a total of 109 H7N9 cases had been reported within mainland China, including 23 deaths. However, Anne Kelso , director of the WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Australia, reported that researchers had seen a "dramatic slowdown" in human cases in Shanghai after the city's live poultry markets were closed on April 6. On the following day, cases in mainland China rose to 118. On April 28, four provinces, Zhejiang , Shandong , Jiangxi , and Fujian , reported new cases, raising the total number of cases in mainland China to 125 with 24 deaths. On May 2, there were 127 confirmed cases in mainland China, of which 27 were fatal, and including the case in Taiwan there were a total of 128 cases worldwide. On May 6, in a weekly update, China's Ministry of Health announced there were 129 confirmed cases in mainland China with 31 deaths, for a total of 130 cases worldwide. On May 7, Hong Kong's Centre for Health Protection reported that there were 130 confirmed cases of H7N9 avian flu in mainland China following the hospitalization of a 79-year-old woman from China's Jiangxi province, bringing the count to 131 cases. The Ministry of Health of People's Republic of China reported on July 10 that in the month of June, there was only 1 confirmed case, and there were a total of 132 confirmed cases in Mainland China as of June 30, 2013 (43 fatal, 85 patient recovery cases). Though there is a slow increase in the number of cases, China recently warned that the transmission of H7N9 virus might be active again by autumn and winter seasons. In August, Guangdong province confirmed its first case of H7N9 bird flu, a 51-year-old woman in critical condition after having been admitted to a hospital on August 3. As of November 1, 2013 [ update ] , China reported to the WHO that "rare and sporadic human infections with H7N9" have been reported with "the total number of cases reported to 137, including 45 deaths" in China. The CDC and U.S. government H7N9 preparedness efforts have continued over the summer and are "continuing to watch this situation closely". As of December 14, 2013 [ update ] , two cases of H7N9 were reported in Hong Kong. Hong Kong reported its first death from H7N9 on 26 December 2013. On December 31, Taiwan's CDC released a press statement indicating that an 86-year-old man from Jiangsu Province, China, who was visiting Taiwan, became ill and tested positive for H7N9 flu. This is the second case in Taiwan, the first being in April. On January 21, 2014, it was reported that a 31-year-old thoracic surgeon had died four days previously, the first medical professional to die from H7N9 flu. There was no evidence that he had been in contact with live poultry recently. Yuen Kwok-yung, a University of Hong Kong microbiologist, said, "If the diagnosis is confirmed and no [bird] exposure history is elicited, this does point slightly more to the possibility that H7N9 may be more transmissible between humans than H5N1". On January 28, 2014, it was reported by the Chinese Center for Disease Control and Prevention that the virus had killed 20 people in China in 2014, with the total number of human infections at 102. That is comparable to 144 confirmed cases, including 46 deaths, in the whole of 2013. At the end of January, more than half of the cases in 2014 had been in Zhejiang, with another 24 in Guangdong, and eight in Shanghai. The director of the Chinese National Influenza Center, Shu Yuelong, said a large-scale H7N9 epidemic still remains unlikely because the virus has not yet mutated in such a way that would allow person to person transmission. On February 13, 2014, it was reported that a 67-year-old female tourist from China had been diagnosed with the H7N9 virus while visiting Malaysia. In January 2015, A Canadian visitor to China was diagnosed with H7N9 after she returned home to British Columbia . After returning to Canada on January 12, she felt ill on January 14. In June 2015, 15 cases of H7N9 infection were reported in China . Beginning in October 2016 China began experiencing a 5th epidemic of H7N9, the largest since the first epidemic in 2013. For the 5th epidemic, the WHO reported 460 human infections as of early March 2017, which accounts for about one-third of cases ever reported since this strain of influenza virus first appeared in 2013. The cumulative total of laboratory-confirmed cases since the first epidemic is 1,223. About 40 percent have died. As of September 8, 2017, the World Health Organization and CDC reported a total number to 759 infections with 281 deaths for the fifth epidemic. On March 31, 2013, the Centre for Health Protection (CHP) of the Department of Health of Hong Kong and the Chinese National Health and Family Planning Commission notified the World Health Organization of three confirmed human cases of influenza A (H7N9) in Shanghai and Anhui (illness onset between February 19 and March 15, 2013). On April 2, the CHP confirmed four more cases in Jiangsu province , all considered in critical condition in hospitals in Nanjing , Suzhou , and Wuxi . In a statement, the CHP said that no epidemiologic links had been found between the four patients and so far no other H7N9 infections have been identified in 167 of their close contacts. The first reported death associated with H7N9 was an 87-year-old man who died on March 4. A second man, aged 27, died on March 10. On April 3, Chinese authorities reported another death, bringing the number to three. On April 4, the number of reported cases was 14, with 5 deaths. The two victims were a 48-year-old man and a 52-year-old woman, both from Shanghai. On April 5, a farmer, aged 64, living in Huzhou ( Zhejiang province), died, raising the death toll to 6. On April 6, the Chinese Ministry of Health reported 18 positive cases, death toll still at 6. Two days later, positive cases rose to 24 and one death case from Shanghai brought the death toll to 7. On April 9, the Chinese National Health and Family Planning Commission announced "an additional three laboratory-confirmed cases of human infection with influenza A(H7N9) virus." The new patients "are two patients from Jiangsu – an 85-year-old man who became ill on 28 March 2013" and a "25-year-old pregnant woman who became ill on 30 March 2013" and "a 64-year-old man from Shanghai who became ill on 1 April 2013, and died on 7 April 2013". As of April 9, a "total of 24 cases have been laboratory confirmed with influenza A(H7N9) virus in China, including seven deaths, 14 severe cases and three mild cases." In Jiangsu, more than "600 close contacts of the confirmed cases are being closely monitored." In an update on April 11, Xinhua reported 38 identified cases and 10 deaths. According to the WHO , of the 28 patients who had survived their infections, 19 illnesses were severe and 9 were mild. The WHO said they were monitoring 760 close contacts and so far had no evidence of ongoing human-to-human transmission. On April 13, a seven-year-old girl from Beijing was the first confirmed case of H7N9 bird flu outside eastern China. On April 14, Xinhua Chinese state media reported two human cases in central Henan just west of the area where the disease had been centered. Totals included 61 infected and 13 dead. On April 14, Chinese officials also reported the first asymptomatic case in Beijing. A health department notice suggested that a 4-year-old boy had no clinical symptoms and was tested during surveillance of high-risk groups. On April 17, a total of 82 cases had been confirmed, with 17 deaths. On April 18, China reported 87 confirmed cases. On April 20, there were 96 confirmed cases, of which 18 were fatal. On the next day, confirmed cases rose to 102 and fatal cases to 20. On April 22, there were 104 cases with 21 deaths. On April 23, 3 more cases were reported in an update from the WHO . All of the newly reported cases were in older men from eastern China. Two cases came from the Zhejiang province and the third was from the Anhui province. Total cases count reached 108 with 22 deaths. On April 24, a case was confirmed by the Taiwanese Government, marking the first case outside of Mainland China. On April 25, the National Health and Family Planning Commission said that a total of 109 H7N9 cases had been reported within mainland China, including 23 deaths. However, Anne Kelso , director of the WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Australia, reported that researchers had seen a "dramatic slowdown" in human cases in Shanghai after the city's live poultry markets were closed on April 6. On the following day, cases in mainland China rose to 118. On April 28, four provinces, Zhejiang , Shandong , Jiangxi , and Fujian , reported new cases, raising the total number of cases in mainland China to 125 with 24 deaths. On May 2, there were 127 confirmed cases in mainland China, of which 27 were fatal, and including the case in Taiwan there were a total of 128 cases worldwide. On May 6, in a weekly update, China's Ministry of Health announced there were 129 confirmed cases in mainland China with 31 deaths, for a total of 130 cases worldwide. On May 7, Hong Kong's Centre for Health Protection reported that there were 130 confirmed cases of H7N9 avian flu in mainland China following the hospitalization of a 79-year-old woman from China's Jiangxi province, bringing the count to 131 cases. The Ministry of Health of People's Republic of China reported on July 10 that in the month of June, there was only 1 confirmed case, and there were a total of 132 confirmed cases in Mainland China as of June 30, 2013 (43 fatal, 85 patient recovery cases). Though there is a slow increase in the number of cases, China recently warned that the transmission of H7N9 virus might be active again by autumn and winter seasons. In August, Guangdong province confirmed its first case of H7N9 bird flu, a 51-year-old woman in critical condition after having been admitted to a hospital on August 3. As of November 1, 2013 [ update ] , China reported to the WHO that "rare and sporadic human infections with H7N9" have been reported with "the total number of cases reported to 137, including 45 deaths" in China. The CDC and U.S. government H7N9 preparedness efforts have continued over the summer and are "continuing to watch this situation closely". As of December 14, 2013 [ update ] , two cases of H7N9 were reported in Hong Kong. Hong Kong reported its first death from H7N9 on 26 December 2013. On December 31, Taiwan's CDC released a press statement indicating that an 86-year-old man from Jiangsu Province, China, who was visiting Taiwan, became ill and tested positive for H7N9 flu. This is the second case in Taiwan, the first being in April. On January 21, 2014, it was reported that a 31-year-old thoracic surgeon had died four days previously, the first medical professional to die from H7N9 flu. There was no evidence that he had been in contact with live poultry recently. Yuen Kwok-yung, a University of Hong Kong microbiologist, said, "If the diagnosis is confirmed and no [bird] exposure history is elicited, this does point slightly more to the possibility that H7N9 may be more transmissible between humans than H5N1". On January 28, 2014, it was reported by the Chinese Center for Disease Control and Prevention that the virus had killed 20 people in China in 2014, with the total number of human infections at 102. That is comparable to 144 confirmed cases, including 46 deaths, in the whole of 2013. At the end of January, more than half of the cases in 2014 had been in Zhejiang, with another 24 in Guangdong, and eight in Shanghai. The director of the Chinese National Influenza Center, Shu Yuelong, said a large-scale H7N9 epidemic still remains unlikely because the virus has not yet mutated in such a way that would allow person to person transmission. On February 13, 2014, it was reported that a 67-year-old female tourist from China had been diagnosed with the H7N9 virus while visiting Malaysia. In January 2015, A Canadian visitor to China was diagnosed with H7N9 after she returned home to British Columbia . After returning to Canada on January 12, she felt ill on January 14. In June 2015, 15 cases of H7N9 infection were reported in China . Beginning in October 2016 China began experiencing a 5th epidemic of H7N9, the largest since the first epidemic in 2013. For the 5th epidemic, the WHO reported 460 human infections as of early March 2017, which accounts for about one-third of cases ever reported since this strain of influenza virus first appeared in 2013. The cumulative total of laboratory-confirmed cases since the first epidemic is 1,223. About 40 percent have died. As of September 8, 2017, the World Health Organization and CDC reported a total number to 759 infections with 281 deaths for the fifth epidemic. According to the World Health Organization, symptoms include fever, cough, and shortness of breath, which may progress to severe pneumonia . The virus can also overload the immune system, causing what is known as a cytokine storm . Blood poisoning and organ failure are also possible. In an article in the New England Journal of Medicine , doctors reported that most of the patients with confirmed cases of H7N9 virus infection were critically ill and that approximately 20% had died of acute respiratory distress syndrome (ARDS) or multiorgan failure . Antigenic and genome sequencing suggests that H7N9 is sensitive to neuraminidase inhibitors , such as oseltamivir and zanamivir . The use of these neuraminidase inhibitors in cases of early infection may be effective, although the benefits of oseltamivir treatment have been questioned. Information released in 2014 indicated that 75% of those that came down with H7N9 influenza had previously been exposed to domestic poultry. In April, 2013, the World Health Organization (WHO) said H7N9 was "unlikely" to become a pandemic and that there was no evidence of human-to-human transmission. In late July, 2013, however, Chinese scientists found evidence that person-to-person transmission was possible, but would not transmit easily. In April 2013, it was also reported that the virus had been found only in chickens, ducks, and pigeons at live poultry markets and that no migratory birds had tested positive for the virus, easing concerns about that route of transmission. However, later investigation demonstrated that H7N9 may infect wild songbirds and caged parakeets, which then shed the virus into their environment. This finding implies that these birds may potentially serve as intermediate hosts with the ability to facilitate transmission and dissemination of H7N9. At an April 26 news conference, the WHO assistant director-general for health stated, "This is an unusually dangerous virus for humans. We think this virus is more easily transmitted from poultry to humans than H5N1 ." Furthermore, there is great concern because unlike the H5N1 virus, H7N9 does not cause visible disease in poultry, which makes surveillance, prevention, and control of the virus in poultry extremely difficult. On April 30, it was announced that the Ministry of Agriculture of the People's Republic of China had asked the Director General of the World Organisation for Animal Health (OIE) to send OIE experts to assess the situation and provide advice. According to the information and data collected, it was confirmed that many of the human cases of H7N9 appeared to have a link with live bird markets, but to that date no human cases or animal infections of H7N9 had been detected on poultry farms. The OIE experts made the hypothesis that people could be infected through exposure to infected birds in markets or to a contaminated environment such as live poultry markets where the virus is present. They believe that live bird markets may play a key role in human and animal infections with H7N9 and that, even if the overall level of infection is relatively low (having not been detected yet in poultry farms), live bird markets provide an environment for amplification and maintenance of the H7N9 virus. The OIE mission also confirmed that currently infection with H7N9 does not cause visible disease in poultry and therefore veterinary services must be especially involved in preventing its further spread. According to the April 30 report, there is no evidence to suggest that the consumption of poultry or eggs could transmit the virus to humans. More assessment is needed to know whether poultry vaccination could be considered as a control option for H7N9. It will also be important to verify whether the H7N9 virus is transmissible from humans to animals because if established, it could be a potential channel for the global spread of the virus. The number of cases detected after April fell abruptly. The decrease in the number of new human H7N9 cases may have resulted from containment measures taken by Chinese authorities, including closing live bird markets, or from a change in seasons, or a possibly a combination of both factors. Studies indicate that avian influenza viruses have a seasonal pattern, much like human seasonal influenza viruses. If this is the case, H7N9 infections – in birds and people – may pick up again when the weather turns cooler in China. Limited person-to-person spread of bird flu is thought to have occurred rarely in the past, most notably with avian influenza A (H5N1). According to the US CDC, based on previous experience, some limited human-to-human spread of this H7N9 virus would not be surprising if the virus reemerges in the fall. Furthermore, according to the WHO, since migratory birds were first implicated in H7N9 transmission, the possibility that the virus may spread into other regions or countries with colder weather cannot be excluded, given the widespread bird migratory patterns. In a study published in July 2013, an international team led by Yoshihiro Kawaoka , one of the world's leading experts on avian flu, reported that while avian flu viruses typically lack the ability to transfer through respiratory droplets, studies using ferrets , who like humans infect one another through coughing and sneezing, showed that one of the H7N9 strains isolated from humans can transmit through respiratory droplets. Kawaoka says, "H7N9 viruses combine several features of pandemic influenza viruses, that is their ability to bind to and replicate in human cells and the ability to transmit via respiratory droplets." Further, because several instances of human-to-human infection are suspected, Kawaoka stated that "If H7N9 viruses acquire the ability to transmit efficiently from person to person, a worldwide outbreak is almost certain since humans lack protective immune responses to these types of viruses." On August 6, 2013, the British Medical Journal released the results of epidemiological investigations conducted after a family cluster of two patients were infected with avian H7N9 in March 2013 and later died in April and May. A 60-year-old man became infected after an exposure to poultry and his daughter, who had not been exposed to poultry but had cared for her ill father, became infected as well. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty-three close contacts of the infected patients did not become ill and they all tested negative for haemagglutination inhibition antibodies specific for avian H7N9. It was concluded that the infection of the daughter probably resulted from close contact with her father during unprotected exposure, suggesting that the virus was able to transmit from person to person. However, the researchers consider the transmissibility of the virus to have remained limited and non-sustainable. In a study published in July 2013, an international team led by Yoshihiro Kawaoka , one of the world's leading experts on avian flu, reported that while avian flu viruses typically lack the ability to transfer through respiratory droplets, studies using ferrets , who like humans infect one another through coughing and sneezing, showed that one of the H7N9 strains isolated from humans can transmit through respiratory droplets. Kawaoka says, "H7N9 viruses combine several features of pandemic influenza viruses, that is their ability to bind to and replicate in human cells and the ability to transmit via respiratory droplets." Further, because several instances of human-to-human infection are suspected, Kawaoka stated that "If H7N9 viruses acquire the ability to transmit efficiently from person to person, a worldwide outbreak is almost certain since humans lack protective immune responses to these types of viruses." On August 6, 2013, the British Medical Journal released the results of epidemiological investigations conducted after a family cluster of two patients were infected with avian H7N9 in March 2013 and later died in April and May. A 60-year-old man became infected after an exposure to poultry and his daughter, who had not been exposed to poultry but had cared for her ill father, became infected as well. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty-three close contacts of the infected patients did not become ill and they all tested negative for haemagglutination inhibition antibodies specific for avian H7N9. It was concluded that the infection of the daughter probably resulted from close contact with her father during unprotected exposure, suggesting that the virus was able to transmit from person to person. However, the researchers consider the transmissibility of the virus to have remained limited and non-sustainable. In the month following the report of the first patient, more than 100 people had been infected, an unusually high rate for a new infection; a fifth of those patients had died, a fifth had recovered, and the rest remained critically ill. Keiji Fukuda , the World Health Organization 's (WHO) assistant director-general for health, security and the environment, identified H7N9 as "...an unusually dangerous virus for humans." By early May 2013, the number of new cases sharply declined and the mortality rate remained at about 20%. As of 2019, the laboratory-confirmed patient fatality risk of H7N9 infection is 39%. However, laboratory-confirmation is biased towards detecting the severest patients. People with H7N9 can have a wide range of symptoms, including asymptomatic and mild infections, but the rate of such infections is less understood. Based on the influenza-like illness surveillance system in China, the number of symptomatic H7N9 infections is likely substantially higher than the number of laboratory-confirmed cases. The estimated symptomatic case fatality risk is 0.16% in the 2013 wave and 0.10% in the 2013/14 wave. A serological study conducted in Guangzhou from December 2013 to April 2014 estimated 3,200 times the number of laboratory-confirmed cases during the same period of time and, for the first time, estimated the infection fatality risk for H7N9 to be 0.036% in the 2013/2014 wave. Researchers have commented on the unusual prevalence of older males among H7N9-infected patients. Two-thirds of persons who are ill from H7N9 are 50 years of age or older, which is an older age curve than that for H5N1 . In addition, two-thirds of persons infected by H7N9 are male. Possible reasons for the prevalence of older males among H7N9-infected patients include: a difference in exposure between males and females due to gender-associated practices; biological differences between males and females; and the differences in healthcare-seeking behavior and healthcare access between males and females. Both the median age and male to female relationship appear to have remained stable: The February 2014, WHO report stated "...37 cases, the median age was 60 years, ranging from 5-84 years, with a male to female ratio of 3.6:1." Dr. Yuzo Arima and his colleagues at WHO report "While poultry exposure appears to be a common risk factor, the age distribution among reported cases also raises the question why so few young adults (i.e. those of working age exposed to poultry as vendors/LBM [ live bird market ] workers/breeders/transporters) have been reported. This not only suggests greater exposure among elderly men but also a possible greater biological susceptibility to more severe outcomes." Danuta M. Skowronski, MD, of the British Columbia Centre for Disease Control and three colleagues put forward the hypothesis that older Chinese men have more lifetime exposure to H7 avian flu viruses and thus have immune responses which are weakly cross-reactive but not protective. This immune phenomenon is called antibody-dependent enhancement (ADE), and is perhaps best known in cases of Dengue fever when a person who has previously been infected with one serotype of Dengue fever becomes infected many months or years later with a different serotype. It is thought to occur when weakly cross-reactive antibodies form bridging complexes to facilitate uptake and replication of related but non-identical variants. Although China has been praised for its quick response, some experts believe that there would be great difficulty providing adequate supplies of a vaccine if the virus were to develop into a pandemic. According to an article in the Journal of the American Medical Association (JAMA) in May 2013, "Even with additional vaccine manufacturing capacity... the global public health community remains woefully underprepared for an effective vaccine response to a pandemic...There is no reason to believe that a yet-to-be-developed pandemic A(H7N9) vaccine will perform any better than existing seasonal vaccines or the A(H1N1)pdm09 vaccines [about 60% to 70% effectiveness], particularly with regard to vaccine efficacy in persons older than 65 years." On October 26, 2013, Chinese scientists announced that they had successfully produced an H7N9 vaccine , the first influenza vaccine to be developed entirely in China. It was developed jointly by researchers from Zhejiang University , Hong Kong University , the Chinese Center for Disease Control and Prevention , China's National Institute for Food and Drug Control, and the Chinese Academy of Medical Sciences . Chinese National Influenza Center director Shu Yuelong said the vaccine passed tests on ferrets and had been approved for humans, but H7N9 has not spread far enough to merit widespread vaccination. The vaccine was developed from a throat swab of an infected patient taken April 3. On November 12, 2013, US scientists at Novavax, Inc. announced their successful clinical testing of an H7N9 vaccine in the New England Journal of Medicine. They had previously described the development, manufacture, and efficacy in mice of an A/Anhui/1/13 (H7N9) viruslike particle (VLP) vaccine produced in insect cells with the use of recombinant baculovirus. The vaccine combined the HA and neuraminidase (NA) of A/Anhui/1/13 with the matrix 1 protein (M1) of A/Indonesia/5/05. The study enrolled 284 adults (≥18 years of age) in a randomized, observer-blinded, placebo-controlled clinical trial of this vaccine. The Centers for Disease Control and Prevention (CDC) began sequencing and development of a vaccine as routine procedure for any new transgenic virus. The CDC and vaccine manufacturers are developing a candidate virus to be used in vaccine manufacturing if there is widespread transmission. On September 18, 2013, NIH announced that researchers have begun testing an investigational H7N9 influenza vaccine in humans. Two Phase II trials are collecting data about the safety of the vaccine, immune system responses to different vaccine dosages, both with and without adjuvants. Healthy adults 19 to 64 years of age will be enrolled in the two studies. The inactivated-virus vaccine was made with H7N9 virus that was isolated in Shanghai, China. Adjuvants are being tested with the vaccine to determine if an adequate immune response can be produced. In addition, during a pandemic, adjuvants may be used as part of a "dose-sparing strategy". In response to a request from the CDC and the Biomedical Advanced Research and Development Authority , following the unprecedented immediate release of the H7N9 flu virus gene sequences from the first human cases, by scientists at the China CDC through the GISAID Initiative, the J. Craig Venter Institute , and Synthetic Genomics Vaccines, Inc. began working with Novartis to synthesize the genes of the new viral strain, and supplied these synthesized genes to the CDC. The scientific community has praised China for its transparency and rapid response to the outbreak of H7N9. In an editorial on April 24, 2013, the journal Nature said "China deserves credit for its rapid response to the outbreaks of H7N9 avian influenza, and its early openness in the reporting and sharing of data." This, in spite of initial worries by Chinese scientists and officials that they might lose credit for their work in isolating and sequencing the novel H7N9 virus, after learning that pharmaceutical company Novartis and the J. Craig Venter Institute had used their sequences to develop US-funded H7N9 vaccine without offering to collaborate with the Chinese team, according to Nature. They believed, the usage of their data was initially not handled in the spirit of the GISAID sharing mechanism, which requires scientists who use the sequences to credit and propose collaboration with those who deposited the data in GISAID. Nature cited a Chinese official who concluded that this situation was quickly mitigated once communication channels were opened and the parties agreed to collaborate, thanks to GISAID president Peter Bogner . Despite concerns that vaccination of poultry against the H5N1 avian influenza virus over the last decade might have made it harder for Chinese veterinary technicians to spot the recent spread of the H7N9 virus, China's Agriculture Ministry defended its policy of large-scale vaccination of poultry against the earlier bird flu strain, saying that it was not interfering with its efforts now to identify the emerging H7N9 virus. On April 15, 2013, the RIWI Corporation, led by researcher Neil Seeman of the University of Toronto released data on 7,016 Chinese "fresh" (i.e. non-panel based) Internet users – with a 24.08% response rate – over 20 hours. The level of contagion awareness was 31% in Beijing, 38% in Hangzhou, 33% in Nanjing, 40% in Shanghai, 52% in Ürümqi, and 28% in Zhengzhou (Chi Square; P = 0.05). The result far exceeds that of other internet surveys, suggesting an intense relevancy of interest and sense of urgency related to the current disease outbreak in the minds of average Chinese citizens. In April 2013, Shanghai's health ministry ordered culling of birds after pigeon samples collected at the Huhuai wholesale agricultural products market in Songjiang District of Shanghai showed H7N9 On April 4, 2013, Shanghai authorities closed a live-poultry-trading zone and began slaughtering all birds. Poultry trading areas in two other areas of the Minhang district were also closed. On April 6, 2013, all Shanghai live poultry markets closed temporarily in response to the H7N9 found in the pigeon samples. The same day, Hangzhou also closed its live poultry markets. After gene sequence analysis, the national avian flu reference laboratory concluded that the strain of the H7N9 virus found on pigeons was highly congenic with those found on persons infected with H7N9 virus, the ministry said. On April 22, 2013, Forbes quoted Chinese state media reporting $2.7 billion in poultry industry losses. When January 2014 brought a dramatic increase in reports of disease, the Chinese government responded by halting live poultry trading in three cities in Zhejiang province where 49 cases and 12 deaths had been reported. In addition, live poultry trading in Shanghai was halted for three months. In Hong Kong, authorities reacted to the discovery of H7N9 in live chickens from the province of Guangdong by suspending imports of fresh poultry from mainland China for 21 days, culling 20,000 chickens, and other measures in an effort to control the spread of the virus. On February 18, 2014, it was announced that the Chinese government would extend the ban for four months. The health minister also said that they plan to prevent diseased birds from entering the market by setting up a facility where imported poultry can be quarantined to ensure they are disease-free. In April 2013, Shanghai's health ministry ordered culling of birds after pigeon samples collected at the Huhuai wholesale agricultural products market in Songjiang District of Shanghai showed H7N9 On April 4, 2013, Shanghai authorities closed a live-poultry-trading zone and began slaughtering all birds. Poultry trading areas in two other areas of the Minhang district were also closed. On April 6, 2013, all Shanghai live poultry markets closed temporarily in response to the H7N9 found in the pigeon samples. The same day, Hangzhou also closed its live poultry markets. After gene sequence analysis, the national avian flu reference laboratory concluded that the strain of the H7N9 virus found on pigeons was highly congenic with those found on persons infected with H7N9 virus, the ministry said. On April 22, 2013, Forbes quoted Chinese state media reporting $2.7 billion in poultry industry losses. When January 2014 brought a dramatic increase in reports of disease, the Chinese government responded by halting live poultry trading in three cities in Zhejiang province where 49 cases and 12 deaths had been reported. In addition, live poultry trading in Shanghai was halted for three months. In Hong Kong, authorities reacted to the discovery of H7N9 in live chickens from the province of Guangdong by suspending imports of fresh poultry from mainland China for 21 days, culling 20,000 chickens, and other measures in an effort to control the spread of the virus. On February 18, 2014, it was announced that the Chinese government would extend the ban for four months. The health minister also said that they plan to prevent diseased birds from entering the market by setting up a facility where imported poultry can be quarantined to ensure they are disease-free. The WHO did not advise against travel to China at that point in time, as there was no evidence of human-to-human transmission of the virus. On April 9, 2013, the Centers for Disease Control and Prevention (CDC) activated its Emergency Operations Center (EOC) in Atlanta at Level II, the second-highest level of alert. Activation was prompted because the novel H7N9 avian influenza virus has never been seen before in animals or humans and because reports from China have linked it to severe human disease. EOC activation will "ensure that internal connections are developed and maintained and that CDC staff are kept informed and up to date with regard to the changing situation." On April 10, 2013, the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA) spelled out bio-safety guidance for handling the H7N9 virus. They stated that work with live cultures must be conducted in biosafety level 3 (BSL-3) containment. They also said that studies growing H7N9 virus should not be done in labs that culture human influenza viruses and that personnel should not have contact with susceptible animals for 5 days after handling H7N9 samples. Malaysia announced that it would temporarily ban Chinese chicken imports. Vietnam announced that it would temporarily ban Chinese poultry imports. All hospitals were informed to remain vigilant, and to notify Singapore's Ministry of Health (MOH) immediately of any suspected cases of avian influenza in individuals who have recently returned from affected areas in China. MOH advised returning travellers from affected areas in China (Shanghai, Anhui, Jiangsu, and Zhejiang) to look out for signs and symptoms of respiratory illness, such as fever and cough, and seek early medical attention if they are ill with such symptoms. MOH also advised individuals to inform their doctors of their travel history, should they develop these symptoms after returning to Singapore. On 3 April 2013, the Executive Yuan activated Taiwan's Central Epidemic Command Center (CECC) in response to the epidemic in mainland China. The Executive Yuan deactivated the CECC for H7N9 influenza on 11 April 2014. During this period, 24 meetings were convened with representatives from 24 central government agencies including the Council of Agriculture, the Ministry of Transportation and Communications, and the Ministry of Education, along with 22 city and county governments. Meetings were attended by regional commanding officers and deputy commanding officers of the Communicable Disease Control Network. On 17 May 2013, a ban became effective on the slaughtering of live poultry at traditional wet markets, which eliminated the risk of animal-to-human transmission of avian influenza.

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Pandemic influenza

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Influenza A virus subtype H2N3

H2N3 is a subtype of the influenza A virus . Its name derives from the forms of the two kinds of proteins on the surface of its coat, hemagglutinin (H) and neuraminidase (N). H2N3 viruses can infect birds and mammals .According to research published by the US National Institutes of Health , the triple reassortant H2N3 virus isolated from diseased pigs in the United States in 2006 is pathogenic for certain mammals without prior adaptation and transmits among swine and ferrets . Adaptation, in the H2 hemagglutinin derived from an avian virus, includes the ability to bind to the mammalian receptor, a significant prerequisite for infection of mammals, in particular humans, which poses a big concern for public health . Researchers investigated the pathogenic potential of swine H2N3 in Cynomolgus macaques , a surrogate model for human influenza infection. In contrast to human H2N2 virus, which served as a control and largely caused mild pneumonia similar to seasonal influenza A viruses, the swine H2N3 virus was more pathogenic causing severe pneumonia in nonhuman primates. Both viruses replicated in the entire respiratory tract, but only swine H2N3 could be isolated from lung tissue on day 6 post infection. All animals cleared the infection whereas swine H2N3 infected macaques still presented with pathologic changes indicative of chronic pneumonia at day 14 post infection. Swine H2N3 virus was also detected to significantly higher titers in nasal and oral swabs indicating the potential for animal-to-animal transmission. Blood plasma levels of Interleukin 6 (IL-6), Interleukin 8 , monocyte chemotactic protein-1 and Interferon-gamma were significantly increased in swine H2N3 compared to human H2N2 infected animals supporting the previously published notion of increased IL-6 levels being a potential marker for severe influenza infections. Researchers concluded the swine H2N3 virus represents a threat to humans with the potential for causing a larger outbreak in a non-immune or partially immune population. Furthermore, surveillance efforts in farmed pig populations need to become an integral part of any epidemic and pandemic influenza preparedness.

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Pandemic influenza

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1626 influenza pandemic

In 1626 an influenza pandemic spread from Asia to Europe, Africa, North America, and South America during the first such pandemic of the seventeenth century.Pandemic influenza yet again spread from Anatolia to Europe and Africa through the bustling, international ports of Constantinople . [ citation needed ]In Europe it started in the southern part of the continent, beginning in Italy and nations bordering the Ottoman Empire. European chronicler surnamed Donius, possibly J. B. Donius, described the outbreak in Italy: "The year 1626 is recent in memory, for which winter began with a greatest influence not only in Rome but all of Italy affected together. This was strongly due to the Borcæ wind that followed the southern winds, which stirred up dangerous and corrupt illnesses that were ridiculously called Castrone." Donius, like many physicians before the discovery of pathogens, attributed the cause of the generalized outbreaks of respiratory illness to climate. Influenza diffused throughout Italy. An epidemic hit the Spanish galleys stationed at the port of Genoa . Physicians in England were by then aware that "Colds" occurred in varying degrees, attributing most sudden respiratory illnesses to "humors" affecting the lungs. European chronicler surnamed Donius, possibly J. B. Donius, described the outbreak in Italy: "The year 1626 is recent in memory, for which winter began with a greatest influence not only in Rome but all of Italy affected together. This was strongly due to the Borcæ wind that followed the southern winds, which stirred up dangerous and corrupt illnesses that were ridiculously called Castrone." Donius, like many physicians before the discovery of pathogens, attributed the cause of the generalized outbreaks of respiratory illness to climate. Influenza diffused throughout Italy. An epidemic hit the Spanish galleys stationed at the port of Genoa . Physicians in England were by then aware that "Colds" occurred in varying degrees, attributing most sudden respiratory illnesses to "humors" affecting the lungs. By 1627 the flu had reached epidemic levels in North America. Flu then spread to the West Indies and South America . Patients who were bled suffered far higher mortality rates than patients who weren't. In The Poore Mans Talent (c. 1623), a then-popular book by Thomas Lodge dispensing home remedies for common ailments, treatments include lozenges, broths, and oily, vaporous ointments for "Colds" that arises with a "general alteration and hott fevour..."

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Pandemic influenza

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COVID-19 pandemic

>10% 3–10% 1–3% 0.3–1% 0.1–0.3% 0.03–0.1% 0–0.03% None or no data The COVID-19 pandemic , also known as the coronavirus pandemic , is a global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identified in an outbreak in Wuhan , the capital of Hubei , China, in December 2019, before it spread to other areas of Asia, and then worldwide in early 2020. The World Health Organization (WHO) declared the outbreak a public health emergency of international concern (PHEIC) on 30 January 2020, and assessed the outbreak had become a pandemic on 11 March 2020. The WHO ended the PHEIC on 5 May 2023. As of 22 April 2024 , the pandemic has caused 7,044,637 confirmed deaths, making it the fifth- deadliest pandemic or epidemic in history . COVID-19 symptoms range from asymptomatic to deadly, but most commonly include fever, sore throat , nocturnal cough , and fatigue. Transmission of the virus is often through airborne particles . Mutations have produced many strains (variants) with varying degrees of infectivity and virulence . COVID-19 vaccines were widely deployed in various countries beginning in December 2020. Treatments include novel antiviral drugs and symptom control. Common mitigation measures during the public health emergency included travel restrictions , lockdowns , business restrictions and closures, workplace hazard controls , mask mandates , quarantines, testing systems, and contact tracing of the infected. The pandemic caused severe social and economic disruption around the world, including the largest global recession since the Great Depression . Widespread supply shortages , including food shortages , were caused by supply chain disruptions and panic buying . Reduced human activity led to an unprecedented temporary decrease in pollution . Educational institutions and public areas were partially or fully closed in many jurisdictions, and many events were cancelled or postponed during 2020 and 2021. Telework became much more common for white-collar workers as the pandemic evolved. Misinformation circulated through social media and mass media , and political tensions intensified . The pandemic raised issues of racial and geographic discrimination , health equity , and the balance between public health imperatives and individual rights.In epidemiology , a pandemic is defined as "an epidemic occurring over a very wide area, crossing international boundaries, and usually affecting a large number of people". During the COVID-19 pandemic, as with other pandemics, the meaning of this term has been challenged. During the initial outbreak in Wuhan , the virus and disease were commonly referred to as "coronavirus", "Wuhan coronavirus", "the coronavirus outbreak" and the "Wuhan coronavirus outbreak", with the disease sometimes called "Wuhan pneumonia ". In January 2020, the WHO recommended 2019-nCoV and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma . WHO finalized the official names COVID-19 and SARS-CoV-2 on 11 February 2020. Tedros Adhanom Ghebreyesus explained: CO for corona , VI for virus , D for disease and 19 for when the outbreak was first identified (31 December 2019). WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications. WHO named variants of concern and variants of interest using Greek letters . The initial practice of naming them according to where the variants were identified (e.g. Delta began as the "Indian variant") is no longer common. A more systematic naming scheme reflects the variant's PANGO lineage (e.g., Omicron 's lineage is B.1.1.529) and is used for other variants. SARS-CoV-2 is a virus closely related to bat coronaviruses , pangolin coronaviruses, and SARS-CoV . The first known outbreak (the 2019–2020 COVID-19 outbreak in mainland China ) started in Wuhan , Hubei, China, in December 2019. Many early cases were linked to people who had visited the Huanan Seafood Wholesale Market there, but it is possible that human-to-human transmission began earlier. Molecular clock analysis suggests that the first cases were likely to have been between October and November 2019. The scientific consensus is that the virus is most likely of a zoonotic origin, from bats or another closely related mammal. While other explanations such as speculations that SARS-CoV-2 was accidentally released from a laboratory have been proposed, these are not supported by evidence. Official "case" counts refer to the number of people who have been tested for COVID-19 and whose test has been confirmed positive according to official protocols whether or not they experienced symptomatic disease. Due to the effect of sampling bias , studies which obtain a more accurate number by extrapolating from a random sample have consistently found that total infections considerably exceed the reported case counts. Many countries, early on, had official policies to not test those with only mild symptoms. The strongest risk factors for severe illness are obesity, complications of diabetes , anxiety disorders, and the total number of conditions. During the start of the COVID-19 pandemic it was not clear whether young people were less likely to be infected, or less likely to develop symptoms and be tested. A retrospective cohort study in China found that children and adults were just as likely to be infected. Among more thorough studies, preliminary results from 9 April 2020, found that in Gangelt , the centre of a major infection cluster in Germany, 15 percent of a population sample tested positive for antibodies . Screening for COVID-19 in pregnant women in New York City , and blood donors in the Netherlands, found rates of positive antibody tests that indicated more infections than reported. Seroprevalence -based estimates are conservative as some studies show that persons with mild symptoms do not have detectable antibodies. Initial estimates of the basic reproduction number (R 0 ) for COVID-19 in January 2020 were between 1.4 and 2.5, but a subsequent analysis claimed that it may be about 5.7 (with a 95 percent confidence interval of 3.8 to 8.9). In December 2021, the number of cases continued to climb due to several factors, including new COVID-19 variants. As of that 28 December, 282,790,822 individuals worldwide had been confirmed as infected. As of 14 April 2022 [ update ] , over 500 million cases were confirmed globally. Most cases are unconfirmed, with the Institute for Health Metrics and Evaluation estimating the true number of cases as of early 2022 to be in the billions. As of 10 March 2023 , more than 6.88 million deaths had been attributed to COVID-19. The first confirmed death was in Wuhan on 9 January 2020. These numbers vary by region and over time, influenced by testing volume, healthcare system quality, treatment options, government response, time since the initial outbreak, and population characteristics, such as age, sex, and overall health. Multiple measures are used to quantify mortality. Official death counts typically include people who died after testing positive. Such counts exclude deaths without a test. Conversely, deaths of people who died from underlying conditions following a positive test may be included. Countries such as Belgium include deaths from suspected cases, including those without a test, thereby increasing counts. Official death counts have been claimed to underreport the actual death toll, because excess mortality (the number of deaths in a period compared to a long-term average) data show an increase in deaths that is not explained by COVID-19 deaths alone. Using such data, estimates of the true number of deaths from COVID-19 worldwide have included a range from 18.2 to 33.5 million (≈27.4 million) by 18 November 2023 by The Economist , as well as over 18.5 million by 1 April 2023 by the Institute for Health Metrics and Evaluation and ≈18.2 million (earlier) deaths between 1 January 2020, and 31 December 2021, by a comprehensive international study. Such deaths include deaths due to healthcare capacity constraints and priorities, as well as reluctance to seek care (to avoid possible infection). Further research may help distinguish the proportions directly caused by COVID-19 from those caused by indirect consequences of the pandemic. In May 2022, the WHO estimated the number of excess deaths by the end of 2021 to be 14.9 million compared to 5.4 million reported COVID-19 deaths, with the majority of the unreported 9.5 million deaths believed to be direct deaths due the virus, rather than indirect deaths. Some deaths were because people with other conditions could not access medical services . A December 2022 WHO study estimated excess deaths from the pandemic during 2020 and 2021, again concluding ≈14.8 million excess early deaths occurred, reaffirming and detailing their prior calculations from May as well as updating them, addressing criticisms. These numbers do not include measures like years of potential life lost and may make the pandemic 2021's leading cause of death . The time between symptom onset and death ranges from 6 to 41 days, typically about 14 days. Mortality rates increase as a function of age. People at the greatest mortality risk are the elderly and those with underlying conditions. The infection fatality ratio (IFR) is the cumulative number of deaths attributed to the disease divided by the cumulative number of infected individuals (including asymptomatic and undiagnosed infections and excluding vaccinated infected individuals). It is expressed in percentage points. Other studies refer to this metric as the infection fatality risk . In November 2020, a review article in Nature reported estimates of population-weighted IFRs for various countries, excluding deaths in elderly care facilities, and found a median range of 0.24% to 1.49%. IFRs rise as a function of age (from 0.002% at age 10 and 0.01% at age 25, to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85). These rates vary by a factor of ≈10,000 across the age groups. For comparison, the IFR for middle-aged adults is two orders of magnitude higher than the annualised risk of a fatal automobile accident and much higher than the risk of dying from seasonal influenza . In December 2020, a systematic review and meta-analysis estimated that population-weighted IFR was 0.5% to 1% in some countries (France, Netherlands, New Zealand, and Portugal), 1% to 2% in other countries (Australia, England, Lithuania, and Spain), and about 2.5% in Italy. This study reported that most of the differences reflected corresponding differences in the population's age structure and the age-specific pattern of infections. There have also been reviews that have compared the fatality rate of this pandemic with prior pandemics, such as MERS-CoV. For comparison the infection mortality rate of seasonal flu in the United States is 0.1%, which is 13 times lower than COVID-19. Another metric in assessing death rate is the case fatality ratio (CFR), [lower-alpha 1] which is the ratio of deaths to diagnoses. This metric can be misleading because of the delay between symptom onset and death and because testing focuses on symptomatic individuals. Based on Johns Hopkins University statistics, the global CFR is 1.02 percent ( 6,881,955 deaths for 676,609,955 cases) as of 10 March 2023 . The number varies by region and has generally declined over time. SARS-CoV-2 is a virus closely related to bat coronaviruses , pangolin coronaviruses, and SARS-CoV . The first known outbreak (the 2019–2020 COVID-19 outbreak in mainland China ) started in Wuhan , Hubei, China, in December 2019. Many early cases were linked to people who had visited the Huanan Seafood Wholesale Market there, but it is possible that human-to-human transmission began earlier. Molecular clock analysis suggests that the first cases were likely to have been between October and November 2019. The scientific consensus is that the virus is most likely of a zoonotic origin, from bats or another closely related mammal. While other explanations such as speculations that SARS-CoV-2 was accidentally released from a laboratory have been proposed, these are not supported by evidence. Official "case" counts refer to the number of people who have been tested for COVID-19 and whose test has been confirmed positive according to official protocols whether or not they experienced symptomatic disease. Due to the effect of sampling bias , studies which obtain a more accurate number by extrapolating from a random sample have consistently found that total infections considerably exceed the reported case counts. Many countries, early on, had official policies to not test those with only mild symptoms. The strongest risk factors for severe illness are obesity, complications of diabetes , anxiety disorders, and the total number of conditions. During the start of the COVID-19 pandemic it was not clear whether young people were less likely to be infected, or less likely to develop symptoms and be tested. A retrospective cohort study in China found that children and adults were just as likely to be infected. Among more thorough studies, preliminary results from 9 April 2020, found that in Gangelt , the centre of a major infection cluster in Germany, 15 percent of a population sample tested positive for antibodies . Screening for COVID-19 in pregnant women in New York City , and blood donors in the Netherlands, found rates of positive antibody tests that indicated more infections than reported. Seroprevalence -based estimates are conservative as some studies show that persons with mild symptoms do not have detectable antibodies. Initial estimates of the basic reproduction number (R 0 ) for COVID-19 in January 2020 were between 1.4 and 2.5, but a subsequent analysis claimed that it may be about 5.7 (with a 95 percent confidence interval of 3.8 to 8.9). In December 2021, the number of cases continued to climb due to several factors, including new COVID-19 variants. As of that 28 December, 282,790,822 individuals worldwide had been confirmed as infected. As of 14 April 2022 [ update ] , over 500 million cases were confirmed globally. Most cases are unconfirmed, with the Institute for Health Metrics and Evaluation estimating the true number of cases as of early 2022 to be in the billions. As of 10 March 2023 , more than 6.88 million deaths had been attributed to COVID-19. The first confirmed death was in Wuhan on 9 January 2020. These numbers vary by region and over time, influenced by testing volume, healthcare system quality, treatment options, government response, time since the initial outbreak, and population characteristics, such as age, sex, and overall health. Multiple measures are used to quantify mortality. Official death counts typically include people who died after testing positive. Such counts exclude deaths without a test. Conversely, deaths of people who died from underlying conditions following a positive test may be included. Countries such as Belgium include deaths from suspected cases, including those without a test, thereby increasing counts. Official death counts have been claimed to underreport the actual death toll, because excess mortality (the number of deaths in a period compared to a long-term average) data show an increase in deaths that is not explained by COVID-19 deaths alone. Using such data, estimates of the true number of deaths from COVID-19 worldwide have included a range from 18.2 to 33.5 million (≈27.4 million) by 18 November 2023 by The Economist , as well as over 18.5 million by 1 April 2023 by the Institute for Health Metrics and Evaluation and ≈18.2 million (earlier) deaths between 1 January 2020, and 31 December 2021, by a comprehensive international study. Such deaths include deaths due to healthcare capacity constraints and priorities, as well as reluctance to seek care (to avoid possible infection). Further research may help distinguish the proportions directly caused by COVID-19 from those caused by indirect consequences of the pandemic. In May 2022, the WHO estimated the number of excess deaths by the end of 2021 to be 14.9 million compared to 5.4 million reported COVID-19 deaths, with the majority of the unreported 9.5 million deaths believed to be direct deaths due the virus, rather than indirect deaths. Some deaths were because people with other conditions could not access medical services . A December 2022 WHO study estimated excess deaths from the pandemic during 2020 and 2021, again concluding ≈14.8 million excess early deaths occurred, reaffirming and detailing their prior calculations from May as well as updating them, addressing criticisms. These numbers do not include measures like years of potential life lost and may make the pandemic 2021's leading cause of death . The time between symptom onset and death ranges from 6 to 41 days, typically about 14 days. Mortality rates increase as a function of age. People at the greatest mortality risk are the elderly and those with underlying conditions. The infection fatality ratio (IFR) is the cumulative number of deaths attributed to the disease divided by the cumulative number of infected individuals (including asymptomatic and undiagnosed infections and excluding vaccinated infected individuals). It is expressed in percentage points. Other studies refer to this metric as the infection fatality risk . In November 2020, a review article in Nature reported estimates of population-weighted IFRs for various countries, excluding deaths in elderly care facilities, and found a median range of 0.24% to 1.49%. IFRs rise as a function of age (from 0.002% at age 10 and 0.01% at age 25, to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85). These rates vary by a factor of ≈10,000 across the age groups. For comparison, the IFR for middle-aged adults is two orders of magnitude higher than the annualised risk of a fatal automobile accident and much higher than the risk of dying from seasonal influenza . In December 2020, a systematic review and meta-analysis estimated that population-weighted IFR was 0.5% to 1% in some countries (France, Netherlands, New Zealand, and Portugal), 1% to 2% in other countries (Australia, England, Lithuania, and Spain), and about 2.5% in Italy. This study reported that most of the differences reflected corresponding differences in the population's age structure and the age-specific pattern of infections. There have also been reviews that have compared the fatality rate of this pandemic with prior pandemics, such as MERS-CoV. For comparison the infection mortality rate of seasonal flu in the United States is 0.1%, which is 13 times lower than COVID-19. Another metric in assessing death rate is the case fatality ratio (CFR), [lower-alpha 1] which is the ratio of deaths to diagnoses. This metric can be misleading because of the delay between symptom onset and death and because testing focuses on symptomatic individuals. Based on Johns Hopkins University statistics, the global CFR is 1.02 percent ( 6,881,955 deaths for 676,609,955 cases) as of 10 March 2023 . The number varies by region and has generally declined over time. The infection fatality ratio (IFR) is the cumulative number of deaths attributed to the disease divided by the cumulative number of infected individuals (including asymptomatic and undiagnosed infections and excluding vaccinated infected individuals). It is expressed in percentage points. Other studies refer to this metric as the infection fatality risk . In November 2020, a review article in Nature reported estimates of population-weighted IFRs for various countries, excluding deaths in elderly care facilities, and found a median range of 0.24% to 1.49%. IFRs rise as a function of age (from 0.002% at age 10 and 0.01% at age 25, to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85). These rates vary by a factor of ≈10,000 across the age groups. For comparison, the IFR for middle-aged adults is two orders of magnitude higher than the annualised risk of a fatal automobile accident and much higher than the risk of dying from seasonal influenza . In December 2020, a systematic review and meta-analysis estimated that population-weighted IFR was 0.5% to 1% in some countries (France, Netherlands, New Zealand, and Portugal), 1% to 2% in other countries (Australia, England, Lithuania, and Spain), and about 2.5% in Italy. This study reported that most of the differences reflected corresponding differences in the population's age structure and the age-specific pattern of infections. There have also been reviews that have compared the fatality rate of this pandemic with prior pandemics, such as MERS-CoV. For comparison the infection mortality rate of seasonal flu in the United States is 0.1%, which is 13 times lower than COVID-19. Another metric in assessing death rate is the case fatality ratio (CFR), [lower-alpha 1] which is the ratio of deaths to diagnoses. This metric can be misleading because of the delay between symptom onset and death and because testing focuses on symptomatic individuals. Based on Johns Hopkins University statistics, the global CFR is 1.02 percent ( 6,881,955 deaths for 676,609,955 cases) as of 10 March 2023 . The number varies by region and has generally declined over time. Several variants have been named by WHO and labelled as a variant of concern (VoC) or a variant of interest (VoI). Many of these variants have shared the more infectious D614G . As of May 2023, the WHO had downgraded all variants of concern to previously circulating as these were no longer detected in new infections. Sub-lineages of the Omicron variant (BA.1 – BA.5) were considered separate VoCs by the WHO until they were downgraded in March 2023 as no longer widely circulating. Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste , nasal congestion and runny nose , cough, muscle pain , sore throat , fever, diarrhoea , and breathing difficulties . People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum , shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhoea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of cases. The disease is mainly transmitted via the respiratory route when people inhale droplets and small airborne particles (that form an aerosol ) that infected people exhale as they breathe, talk, cough, sneeze, or sing. Infected people are more likely to transmit COVID-19 when they are physically close to other non-infected individuals. However, infection can occur over longer distances, particularly indoors. SARS‑CoV‑2 belongs to the broad family of viruses known as coronaviruses . It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment. Coronaviruses infect humans, other mammals, including livestock and companion animals, and avian species. Human coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS, fatality rate ≈34%). SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E , NL63 , OC43 , HKU1 , MERS-CoV , and the original SARS-CoV . The standard method of testing for presence of SARS-CoV-2 is a nucleic acid test , which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab ; however, a nasal swab or sputum sample may also be used. The WHO has published several testing protocols for the disease. Preventive measures to reduce the chances of infection include getting vaccinated, staying at home or spending more time outdoors, avoiding crowded places, keeping distance from others, wearing a mask in public, ventilating indoor spaces, managing potential exposure durations, washing hands with soap and water often and for at least twenty seconds, practicing good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands. Those diagnosed with COVID-19 or who believe they may be infected are advised by healthcare authorities to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items. A COVID-19 vaccine is intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID-19 ). Prior to the COVID-19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic and severe illness. The COVID-19 vaccines are widely credited for their role in reducing the severity and death caused by COVID-19. As of March 2023, more than 5.5 billion people had received one or more doses (11.8 billion in total) in over 197 countries. The Oxford-AstraZeneca vaccine was the most widely used. According to a June 2022 study, COVID-19 vaccines prevented an additional 14.4 million to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. On 8 November 2022, the first recombinant protein-based COVID-19 vaccine (Novavax's booster Nuvaxovid ) was authorized for use in adults in the United Kingdom. It has subsequently received endorsement/authorization from the WHO, US, European Union, and Australia. On 12 November 2022, the WHO released its Global Vaccine Market Report. The report indicated that "inequitable distribution is not unique to COVID-19 vaccines"; countries that are not economically strong struggle to obtain vaccines. On 14 November 2022, the first inhalable vaccine was introduced, developed by Chinese biopharmaceutical company CanSino Biologics , in the city of Shanghai, China. For the first two years of the pandemic, no specific and effective treatment or cure was available. In 2021, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) approved the oral antiviral protease inhibitor , Paxlovid (nirmatrelvir plus the HIV antiviral ritonavir ), to treat adult patients. FDA later gave it an EUA. Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), adequate intake of oral fluids and rest. Good personal hygiene and a healthy diet are also recommended. Supportive care in severe cases includes treatment to relieve symptoms , fluid therapy , oxygen support and prone positioning , and medications or devices to support other affected vital organs. More severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is recommended to reduce mortality. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure. Existing drugs such as hydroxychloroquine , lopinavir/ritonavir , and ivermectin are not recommended by US or European health authorities, as there is no good evidence they have any useful effect. The antiviral remdesivir is available in the US, Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for use with mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy. The severity of COVID-19 varies. It may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold . In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to intensive care units (ICU). Between 5% and 50% of COVID-19 patients experience long COVID , a condition characterized by long-term consequences persisting after the typical convalescence period of the disease. The most commonly reported clinical presentations are fatigue and memory problems, as well as malaise , headaches, shortness of breath , loss of smell, muscle weakness , low fever and cognitive dysfunction . Several variants have been named by WHO and labelled as a variant of concern (VoC) or a variant of interest (VoI). Many of these variants have shared the more infectious D614G . As of May 2023, the WHO had downgraded all variants of concern to previously circulating as these were no longer detected in new infections. Sub-lineages of the Omicron variant (BA.1 – BA.5) were considered separate VoCs by the WHO until they were downgraded in March 2023 as no longer widely circulating. Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste , nasal congestion and runny nose , cough, muscle pain , sore throat , fever, diarrhoea , and breathing difficulties . People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum , shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhoea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of cases. The disease is mainly transmitted via the respiratory route when people inhale droplets and small airborne particles (that form an aerosol ) that infected people exhale as they breathe, talk, cough, sneeze, or sing. Infected people are more likely to transmit COVID-19 when they are physically close to other non-infected individuals. However, infection can occur over longer distances, particularly indoors. SARS‑CoV‑2 belongs to the broad family of viruses known as coronaviruses . It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment. Coronaviruses infect humans, other mammals, including livestock and companion animals, and avian species. Human coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS, fatality rate ≈34%). SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E , NL63 , OC43 , HKU1 , MERS-CoV , and the original SARS-CoV . The standard method of testing for presence of SARS-CoV-2 is a nucleic acid test , which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab ; however, a nasal swab or sputum sample may also be used. The WHO has published several testing protocols for the disease. Preventive measures to reduce the chances of infection include getting vaccinated, staying at home or spending more time outdoors, avoiding crowded places, keeping distance from others, wearing a mask in public, ventilating indoor spaces, managing potential exposure durations, washing hands with soap and water often and for at least twenty seconds, practicing good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands. Those diagnosed with COVID-19 or who believe they may be infected are advised by healthcare authorities to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items. A COVID-19 vaccine is intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID-19 ). Prior to the COVID-19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic and severe illness. The COVID-19 vaccines are widely credited for their role in reducing the severity and death caused by COVID-19. As of March 2023, more than 5.5 billion people had received one or more doses (11.8 billion in total) in over 197 countries. The Oxford-AstraZeneca vaccine was the most widely used. According to a June 2022 study, COVID-19 vaccines prevented an additional 14.4 million to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. On 8 November 2022, the first recombinant protein-based COVID-19 vaccine (Novavax's booster Nuvaxovid ) was authorized for use in adults in the United Kingdom. It has subsequently received endorsement/authorization from the WHO, US, European Union, and Australia. On 12 November 2022, the WHO released its Global Vaccine Market Report. The report indicated that "inequitable distribution is not unique to COVID-19 vaccines"; countries that are not economically strong struggle to obtain vaccines. On 14 November 2022, the first inhalable vaccine was introduced, developed by Chinese biopharmaceutical company CanSino Biologics , in the city of Shanghai, China. A COVID-19 vaccine is intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 ( COVID-19 ). Prior to the COVID-19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic and severe illness. The COVID-19 vaccines are widely credited for their role in reducing the severity and death caused by COVID-19. As of March 2023, more than 5.5 billion people had received one or more doses (11.8 billion in total) in over 197 countries. The Oxford-AstraZeneca vaccine was the most widely used. According to a June 2022 study, COVID-19 vaccines prevented an additional 14.4 million to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. On 8 November 2022, the first recombinant protein-based COVID-19 vaccine (Novavax's booster Nuvaxovid ) was authorized for use in adults in the United Kingdom. It has subsequently received endorsement/authorization from the WHO, US, European Union, and Australia. On 12 November 2022, the WHO released its Global Vaccine Market Report. The report indicated that "inequitable distribution is not unique to COVID-19 vaccines"; countries that are not economically strong struggle to obtain vaccines. On 14 November 2022, the first inhalable vaccine was introduced, developed by Chinese biopharmaceutical company CanSino Biologics , in the city of Shanghai, China. For the first two years of the pandemic, no specific and effective treatment or cure was available. In 2021, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) approved the oral antiviral protease inhibitor , Paxlovid (nirmatrelvir plus the HIV antiviral ritonavir ), to treat adult patients. FDA later gave it an EUA. Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), adequate intake of oral fluids and rest. Good personal hygiene and a healthy diet are also recommended. Supportive care in severe cases includes treatment to relieve symptoms , fluid therapy , oxygen support and prone positioning , and medications or devices to support other affected vital organs. More severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is recommended to reduce mortality. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure. Existing drugs such as hydroxychloroquine , lopinavir/ritonavir , and ivermectin are not recommended by US or European health authorities, as there is no good evidence they have any useful effect. The antiviral remdesivir is available in the US, Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for use with mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy. The severity of COVID-19 varies. It may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold . In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to intensive care units (ICU). Between 5% and 50% of COVID-19 patients experience long COVID , a condition characterized by long-term consequences persisting after the typical convalescence period of the disease. The most commonly reported clinical presentations are fatigue and memory problems, as well as malaise , headaches, shortness of breath , loss of smell, muscle weakness , low fever and cognitive dysfunction . Many countries attempted to slow or stop the spread of COVID-19 by recommending, mandating or prohibiting behaviour changes, while others relied primarily on providing information. Measures ranged from public advisories to stringent lockdowns. Outbreak control strategies are divided into elimination and mitigation. Experts differentiate between elimination strategies (known as " zero-COVID ") that aim to completely stop the spread of the virus within the community, and mitigation strategies (commonly known as " flattening the curve ") that attempt to lessen the effects of the virus on society, but which still tolerate some level of transmission within the community. These initial strategies can be pursued sequentially or simultaneously during the acquired immunity phase through natural and vaccine-induced immunity . Nature reported in 2021 that 90 percent of researchers who responded to a survey "think that the coronavirus will become endemic ". Containment is undertaken to stop an outbreak from spreading into the general population. Infected individuals are isolated while they are infectious. The people they have interacted with are contacted and isolated for long enough to ensure that they are either not infected or no longer contagious. Screening is the starting point for containment. Screening is done by checking for symptoms to identify infected individuals, who can then be isolated or offered treatment. The Zero-COVID strategy involves using public health measures such as contact tracing , mass testing , border quarantine , lockdowns and mitigation software to stop community transmission of COVID-19 as soon as it is detected, with the goal of getting the area back to zero detected infections and resuming normal economic and social activities. Successful containment or suppression reduces Rt to less than 1. Should containment fail, efforts focus on mitigation: measures taken to slow the spread and limit its effects on the healthcare system and society. Successful mitigation delays and decreases the epidemic peak, known as "flattening the epidemic curve ". This decreases the risk of overwhelming health services and provides more time for developing vaccines and treatments. Individual behaviour changed in many jurisdictions. Many people worked from home instead of at their traditional workplaces. Non-pharmaceutical interventions that may reduce spread include personal actions such as wearing face masks , self-quarantine, and hand hygiene ; community measures aimed at reducing interpersonal contacts such as closing workplaces and schools and cancelling large gatherings; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such as surface cleaning. More drastic actions, such as quarantining entire populations and strict travel bans have been attempted in various jurisdictions. The Chinese and Australian government approaches have included many lockdowns and are widely considered the most strict. The New Zealand government response included the most severe travel restrictions. As part of its K-Quarantine program, South Korea introduced mass screening and localised quarantines, and issued alerts on the movements of infected individuals. The Singaporean government's response included so-called " circuit breaker lockdowns " and financial support for those affected while also imposing large fines for those who broke quarantine. Contact tracing attempts to identify recent contacts of newly infected individuals, and to screen them for infection; the traditional approach is to request a list of contacts from infectees, and then telephone or visit the contacts. Contact tracing was widely used during the Western African Ebola virus epidemic in 2014. Another approach is to collect location data from mobile devices to identify those who have come in significant contact with infectees, which prompted privacy concerns. On 10 April 2020, Google and Apple announced an initiative for privacy-preserving contact tracing. In Europe and in the US, Palantir Technologies initially provided COVID-19 tracking services. WHO described increasing capacity and adapting healthcare as a fundamental mitigation. The ECDC and WHO's European regional office issued guidelines for hospitals and primary healthcare services for shifting resources at multiple levels, including focusing laboratory services towards testing, cancelling elective procedures, separating and isolating patients, and increasing intensive care capabilities by training personnel and increasing ventilators and beds. The pandemic drove widespread adoption of telehealth . Due to supply chain capacity limitations, some manufacturers began 3D printing material such as nasal swabs and ventilator parts. In one example, an Italian startup received legal threats due to alleged patent infringement after reverse-engineering and printing one hundred requested ventilator valves overnight. Individuals and groups of makers created and shared open source designs, and manufacturing devices using locally sourced materials, sewing, and 3D printing. Millions of face shields , protective gowns, and masks were made. Other ad hoc medical supplies included shoe covers, surgical caps, powered air-purifying respirators , and hand sanitizer . Novel devices were created such as ear savers , non-invasive ventilation helmets, and ventilator splitters. In July 2021, several experts expressed concern that achieving herd immunity may not be possible because Delta can transmit among vaccinated individuals. CDC published data showing that vaccinated people could transmit Delta, something officials believed was less likely with other variants. Consequently, WHO and CDC encouraged vaccinated people to continue with non-pharmaceutical interventions such as masking, social distancing, and quarantining if exposed. Containment is undertaken to stop an outbreak from spreading into the general population. Infected individuals are isolated while they are infectious. The people they have interacted with are contacted and isolated for long enough to ensure that they are either not infected or no longer contagious. Screening is the starting point for containment. Screening is done by checking for symptoms to identify infected individuals, who can then be isolated or offered treatment. The Zero-COVID strategy involves using public health measures such as contact tracing , mass testing , border quarantine , lockdowns and mitigation software to stop community transmission of COVID-19 as soon as it is detected, with the goal of getting the area back to zero detected infections and resuming normal economic and social activities. Successful containment or suppression reduces Rt to less than 1. Should containment fail, efforts focus on mitigation: measures taken to slow the spread and limit its effects on the healthcare system and society. Successful mitigation delays and decreases the epidemic peak, known as "flattening the epidemic curve ". This decreases the risk of overwhelming health services and provides more time for developing vaccines and treatments. Individual behaviour changed in many jurisdictions. Many people worked from home instead of at their traditional workplaces. Non-pharmaceutical interventions that may reduce spread include personal actions such as wearing face masks , self-quarantine, and hand hygiene ; community measures aimed at reducing interpersonal contacts such as closing workplaces and schools and cancelling large gatherings; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such as surface cleaning. More drastic actions, such as quarantining entire populations and strict travel bans have been attempted in various jurisdictions. The Chinese and Australian government approaches have included many lockdowns and are widely considered the most strict. The New Zealand government response included the most severe travel restrictions. As part of its K-Quarantine program, South Korea introduced mass screening and localised quarantines, and issued alerts on the movements of infected individuals. The Singaporean government's response included so-called " circuit breaker lockdowns " and financial support for those affected while also imposing large fines for those who broke quarantine. Contact tracing attempts to identify recent contacts of newly infected individuals, and to screen them for infection; the traditional approach is to request a list of contacts from infectees, and then telephone or visit the contacts. Contact tracing was widely used during the Western African Ebola virus epidemic in 2014. Another approach is to collect location data from mobile devices to identify those who have come in significant contact with infectees, which prompted privacy concerns. On 10 April 2020, Google and Apple announced an initiative for privacy-preserving contact tracing. In Europe and in the US, Palantir Technologies initially provided COVID-19 tracking services. Non-pharmaceutical interventions that may reduce spread include personal actions such as wearing face masks , self-quarantine, and hand hygiene ; community measures aimed at reducing interpersonal contacts such as closing workplaces and schools and cancelling large gatherings; community engagement to encourage acceptance and participation in such interventions; as well as environmental measures such as surface cleaning. More drastic actions, such as quarantining entire populations and strict travel bans have been attempted in various jurisdictions. The Chinese and Australian government approaches have included many lockdowns and are widely considered the most strict. The New Zealand government response included the most severe travel restrictions. As part of its K-Quarantine program, South Korea introduced mass screening and localised quarantines, and issued alerts on the movements of infected individuals. The Singaporean government's response included so-called " circuit breaker lockdowns " and financial support for those affected while also imposing large fines for those who broke quarantine. Contact tracing attempts to identify recent contacts of newly infected individuals, and to screen them for infection; the traditional approach is to request a list of contacts from infectees, and then telephone or visit the contacts. Contact tracing was widely used during the Western African Ebola virus epidemic in 2014. Another approach is to collect location data from mobile devices to identify those who have come in significant contact with infectees, which prompted privacy concerns. On 10 April 2020, Google and Apple announced an initiative for privacy-preserving contact tracing. In Europe and in the US, Palantir Technologies initially provided COVID-19 tracking services. WHO described increasing capacity and adapting healthcare as a fundamental mitigation. The ECDC and WHO's European regional office issued guidelines for hospitals and primary healthcare services for shifting resources at multiple levels, including focusing laboratory services towards testing, cancelling elective procedures, separating and isolating patients, and increasing intensive care capabilities by training personnel and increasing ventilators and beds. The pandemic drove widespread adoption of telehealth . Due to supply chain capacity limitations, some manufacturers began 3D printing material such as nasal swabs and ventilator parts. In one example, an Italian startup received legal threats due to alleged patent infringement after reverse-engineering and printing one hundred requested ventilator valves overnight. Individuals and groups of makers created and shared open source designs, and manufacturing devices using locally sourced materials, sewing, and 3D printing. Millions of face shields , protective gowns, and masks were made. Other ad hoc medical supplies included shoe covers, surgical caps, powered air-purifying respirators , and hand sanitizer . Novel devices were created such as ear savers , non-invasive ventilation helmets, and ventilator splitters. Due to supply chain capacity limitations, some manufacturers began 3D printing material such as nasal swabs and ventilator parts. In one example, an Italian startup received legal threats due to alleged patent infringement after reverse-engineering and printing one hundred requested ventilator valves overnight. Individuals and groups of makers created and shared open source designs, and manufacturing devices using locally sourced materials, sewing, and 3D printing. Millions of face shields , protective gowns, and masks were made. Other ad hoc medical supplies included shoe covers, surgical caps, powered air-purifying respirators , and hand sanitizer . Novel devices were created such as ear savers , non-invasive ventilation helmets, and ventilator splitters. In July 2021, several experts expressed concern that achieving herd immunity may not be possible because Delta can transmit among vaccinated individuals. CDC published data showing that vaccinated people could transmit Delta, something officials believed was less likely with other variants. Consequently, WHO and CDC encouraged vaccinated people to continue with non-pharmaceutical interventions such as masking, social distancing, and quarantining if exposed. The outbreak was discovered in Wuhan in November 2019. It is possible that human-to-human transmission was happening before the discovery. Based on a retrospective analysis starting from December 2019, the number of cases in Hubei gradually increased, reaching 60 by 20 December and at least 266 by 31 December. A pneumonia cluster was observed on 26 December and treated by Chinese pulmonologist Zhang Jixian . She informed the Wuhan Jianghan CDC on 27 December. After analyzing pneumonia patient samples, a genetic sequencing company named Vision Medicals reported the discovery of a novel coronavirus to the China CDC (CCDC) on 28 December. On 30 December, a test report from CapitalBio Medlab addressed to Wuhan Central Hospital reported an erroneous positive result for SARS , causing doctors there to alert authorities. Eight of those doctors, including Li Wenliang (who was also punished on 3 January), were later admonished by the police for spreading false rumours. Director of the Emergency Department at the Central Hospital of Wuhan, Ai Fen, was also reprimanded. That evening, Wuhan Municipal Health Commission (WMHC) issued a notice about "the treatment of pneumonia of unknown cause". The next day, WMHC made the announcement public, confirming 27 cases —enough to trigger an investigation. On 31 December, the WHO office in China was notified about the cluster of unknown pneumonia cases and immediately launched an investigation. Official Chinese sources claimed that the early cases were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020, CCDC director George Gao initially ruled out the market as a possible origin, as animal samples collected there had tested negative. On 11 January, WHO was notified by the Chinese National Health Commission that the outbreak was associated with exposures in the market, and that China had identified a new type of coronavirus, which it isolated on 7 January. Initially, the number of cases doubled approximately every seven and a half days. In early and mid-January, the virus spread to other Chinese provinces , helped by the Chinese New Year migration . Wuhan was a transport hub and major rail interchange. On 10 January, the virus' genome was shared publicly. A retrospective study published in March found that 6,174 people had reported symptoms by 20 January. A 24 January report indicated human transmission was likely occurring, and recommended personal protective equipment for health workers. It also advocated testing, given the outbreak's "pandemic potential". On 31 January, the first published modelling study warned of inevitable "independent self-sustaining outbreaks in major cities globally" and called for "large-scale public health interventions." On 30 January, 7,818 infections had been confirmed, leading WHO to declare the outbreak a Public Health Emergency of International Concern (PHEIC). On 11 March, WHO announced its assessment that the situation could be characterized as a pandemic. By 31 January, Italy indicated its first confirmed infections had occurred, in two tourists from China. On 19 March, Italy overtook China as the country with the most reported deaths. By 26 March, the United States had overtaken China and Italy as the country with the highest number of confirmed infections. Genomic analysis indicated that the majority of New York 's confirmed infections came from Europe, rather than directly from Asia. Testing of prior samples revealed a person who was infected in France on 27 December 2019 and a person in the United States who died from the disease on 6 February. In October, WHO reported that one in ten people around the world may have been infected, or 780 million people, while only 35 million infections had been confirmed. On 9 November, Pfizer released trial results for a candidate vaccine, showing a 90 percent effectiveness in preventing infection. That day, Novavax submitted an FDA Fast Track application for their vaccine. On 14 December, Public Health England reported that a variant had been discovered in the UK's southeast, predominantly in Kent . The variant, later named Alpha , showed changes to the spike protein that could make the virus more infectious. As of 13 December, 1,108 infections had been confirmed in the UK. On 4 February 2020, US Secretary of Health and Human Services Alex Azar waived liability for vaccine manufacturers in all cases except those involving "willful misconduct". On 2 January, the Alpha variant, first discovered in the UK, had been identified in 33 countries. On 6 January, the Gamma variant was first identified in Japanese travellers returning from Brazil. On 29 January, it was reported that the Novavax vaccine was 49 percent effective against the Beta variant in a clinical trial in South Africa. The CoronaVac vaccine was reported to be 50.4 percent effective in a Brazil clinical trial. On 12 March, several countries stopped using the Oxford-AstraZeneca COVID-19 vaccine - due to blood clotting problems, specifically cerebral venous sinus thrombosis (CVST). On 20 March, the WHO and European Medicines Agency found no link to thrombosis , leading several countries to resume administering the vaccine. In March WHO reported that an animal host was the most likely origin, without ruling out other possibilities. The Delta variant was first identified in India. In mid-April, the variant was first detected in the UK and two months later it had become a full-fledged third wave in the country, forcing the government to delay reopening that was originally scheduled for June. On 10 November, Germany advised against the Moderna vaccine for people under 30, due to a possible association with myocarditis . On 24 November, the Omicron variant was detected in South Africa; a few days later the World Health Organization declared it a VoC (variant of concern). The new variant is more infectious than the Delta variant. On 1 January, Europe passed 100 million cases amidst a surge in the Omicron variant . Later that month, the WHO recommended the rheumatoid arthritis drug Baricitinib for severe or critical patients. It also recommended the monoclonal antibody Sotrovimab in patients with non-severe disease, but only those who are at highest risk of hospitalization. On 24 January, the Institute for Health Metrics and Evaluation estimated that about 57% of the world's population had been infected by COVID-19. By 6 March, it was reported that the total worldwide death count had surpassed 6 million people. By 6 July, Omicron subvariants BA.4 and BA.5 had spread worldwide. WHO Director-General Tedros Ghebreyesus stated on 14 September 2022, that "[The world has] never been in a better position to end the pandemic", citing the lowest number of weekly reported deaths since March 2020. He continued, "We are not there yet. But the end is in sight—we can see the finish line". On 21 October, the United States surpassed 99 million cases of COVID-19, the most cases of any country. By 30 October, the worldwide daily death toll was 424, the lowest since 385 deaths were reported on 12 March 2020. 17 November marked the three-year anniversary since health officials in China first detected COVID-19. On 11 November, the WHO reported that deaths since the month of February had dropped 90 percent. Director-General Tedros said this was "cause for optimism". On 3 December, the WHO indicated that, "at least 90% of the world's population has some level of immunity to Sars-CoV-2". In early December, China began lifting some of its most stringent lockdown measures. Subsequent data from China's health authorities revealed that 248 million people, nearly 18 percent of its population, had been infected in the first 20 days of that month. On 29 December, the US joined Italy, Japan, Taiwan and India in requiring negative COVID-19 test results from all people traveling from China due to the new surge in cases. The EU refused similar measures, stating that the BF7 omicron variant had already spread throughout Europe without becoming dominant. On 4 January 2023, the World Health Organization said the information shared by China during the recent surge in infections lacked data, such as hospitalization rates. On 10 January, the WHO's Europe office said the recent viral surge in China posed "no immediate threat." On 16 January, the WHO recommended that China monitor excess mortality to provide "a more comprehensive understanding of the impact of COVID-19." On 30 January, the three-year anniversary of the original declaration, the World Health Organization determined that COVID-19 still met the criteria for a public health emergency of international concern (PHEIC). On 19 March, WHO Director-General Tedros indicated he was "confident" the COVID-19 pandemic would cease to be a public health emergency by the end of the year. On 5 May, the WHO downgraded COVID-19 from being a global health emergency, though it continued to refer to it as a pandemic. The WHO does not make official declarations of when pandemics end. The decision came after Tedros convened with the International Health Regulations Emergency Committee, wherein the Committee noted that due to the decrease in deaths and hospitalisations, and the prevalence of vaccinations and the level of general immunity, it was time to remove the emergency designation and "transition to long-term management". Tedros agreed, and the WHO reduced the classification to an "established and ongoing health issue". In a press conference, Tedros remarked that the diminishing threat from COVID-19 had "allowed most countries to return to life as we knew it before COVID-19". In September the WHO said it had observed "concerning" trends in COVID-19 case numbers and hospitalisations, although analysis was hampered because many countries were no longer recording COVID-19 case statistics. In November 2023, in response to viral mutations and changing characteristics of infection, the WHO adjusted its treatment guidelines. Among other changes, remdesivir and molnupiravir were now recommended only for the most severe cases, and deuremidevir and ivermectin were recommended against. The outbreak was discovered in Wuhan in November 2019. It is possible that human-to-human transmission was happening before the discovery. Based on a retrospective analysis starting from December 2019, the number of cases in Hubei gradually increased, reaching 60 by 20 December and at least 266 by 31 December. A pneumonia cluster was observed on 26 December and treated by Chinese pulmonologist Zhang Jixian . She informed the Wuhan Jianghan CDC on 27 December. After analyzing pneumonia patient samples, a genetic sequencing company named Vision Medicals reported the discovery of a novel coronavirus to the China CDC (CCDC) on 28 December. On 30 December, a test report from CapitalBio Medlab addressed to Wuhan Central Hospital reported an erroneous positive result for SARS , causing doctors there to alert authorities. Eight of those doctors, including Li Wenliang (who was also punished on 3 January), were later admonished by the police for spreading false rumours. Director of the Emergency Department at the Central Hospital of Wuhan, Ai Fen, was also reprimanded. That evening, Wuhan Municipal Health Commission (WMHC) issued a notice about "the treatment of pneumonia of unknown cause". The next day, WMHC made the announcement public, confirming 27 cases —enough to trigger an investigation. On 31 December, the WHO office in China was notified about the cluster of unknown pneumonia cases and immediately launched an investigation. Official Chinese sources claimed that the early cases were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020, CCDC director George Gao initially ruled out the market as a possible origin, as animal samples collected there had tested negative. On 11 January, WHO was notified by the Chinese National Health Commission that the outbreak was associated with exposures in the market, and that China had identified a new type of coronavirus, which it isolated on 7 January. Initially, the number of cases doubled approximately every seven and a half days. In early and mid-January, the virus spread to other Chinese provinces , helped by the Chinese New Year migration . Wuhan was a transport hub and major rail interchange. On 10 January, the virus' genome was shared publicly. A retrospective study published in March found that 6,174 people had reported symptoms by 20 January. A 24 January report indicated human transmission was likely occurring, and recommended personal protective equipment for health workers. It also advocated testing, given the outbreak's "pandemic potential". On 31 January, the first published modelling study warned of inevitable "independent self-sustaining outbreaks in major cities globally" and called for "large-scale public health interventions." On 30 January, 7,818 infections had been confirmed, leading WHO to declare the outbreak a Public Health Emergency of International Concern (PHEIC). On 11 March, WHO announced its assessment that the situation could be characterized as a pandemic. By 31 January, Italy indicated its first confirmed infections had occurred, in two tourists from China. On 19 March, Italy overtook China as the country with the most reported deaths. By 26 March, the United States had overtaken China and Italy as the country with the highest number of confirmed infections. Genomic analysis indicated that the majority of New York 's confirmed infections came from Europe, rather than directly from Asia. Testing of prior samples revealed a person who was infected in France on 27 December 2019 and a person in the United States who died from the disease on 6 February. In October, WHO reported that one in ten people around the world may have been infected, or 780 million people, while only 35 million infections had been confirmed. On 9 November, Pfizer released trial results for a candidate vaccine, showing a 90 percent effectiveness in preventing infection. That day, Novavax submitted an FDA Fast Track application for their vaccine. On 14 December, Public Health England reported that a variant had been discovered in the UK's southeast, predominantly in Kent . The variant, later named Alpha , showed changes to the spike protein that could make the virus more infectious. As of 13 December, 1,108 infections had been confirmed in the UK. On 4 February 2020, US Secretary of Health and Human Services Alex Azar waived liability for vaccine manufacturers in all cases except those involving "willful misconduct". On 2 January, the Alpha variant, first discovered in the UK, had been identified in 33 countries. On 6 January, the Gamma variant was first identified in Japanese travellers returning from Brazil. On 29 January, it was reported that the Novavax vaccine was 49 percent effective against the Beta variant in a clinical trial in South Africa. The CoronaVac vaccine was reported to be 50.4 percent effective in a Brazil clinical trial. On 12 March, several countries stopped using the Oxford-AstraZeneca COVID-19 vaccine - due to blood clotting problems, specifically cerebral venous sinus thrombosis (CVST). On 20 March, the WHO and European Medicines Agency found no link to thrombosis , leading several countries to resume administering the vaccine. In March WHO reported that an animal host was the most likely origin, without ruling out other possibilities. The Delta variant was first identified in India. In mid-April, the variant was first detected in the UK and two months later it had become a full-fledged third wave in the country, forcing the government to delay reopening that was originally scheduled for June. On 10 November, Germany advised against the Moderna vaccine for people under 30, due to a possible association with myocarditis . On 24 November, the Omicron variant was detected in South Africa; a few days later the World Health Organization declared it a VoC (variant of concern). The new variant is more infectious than the Delta variant. On 1 January, Europe passed 100 million cases amidst a surge in the Omicron variant . Later that month, the WHO recommended the rheumatoid arthritis drug Baricitinib for severe or critical patients. It also recommended the monoclonal antibody Sotrovimab in patients with non-severe disease, but only those who are at highest risk of hospitalization. On 24 January, the Institute for Health Metrics and Evaluation estimated that about 57% of the world's population had been infected by COVID-19. By 6 March, it was reported that the total worldwide death count had surpassed 6 million people. By 6 July, Omicron subvariants BA.4 and BA.5 had spread worldwide. WHO Director-General Tedros Ghebreyesus stated on 14 September 2022, that "[The world has] never been in a better position to end the pandemic", citing the lowest number of weekly reported deaths since March 2020. He continued, "We are not there yet. But the end is in sight—we can see the finish line". On 21 October, the United States surpassed 99 million cases of COVID-19, the most cases of any country. By 30 October, the worldwide daily death toll was 424, the lowest since 385 deaths were reported on 12 March 2020. 17 November marked the three-year anniversary since health officials in China first detected COVID-19. On 11 November, the WHO reported that deaths since the month of February had dropped 90 percent. Director-General Tedros said this was "cause for optimism". On 3 December, the WHO indicated that, "at least 90% of the world's population has some level of immunity to Sars-CoV-2". In early December, China began lifting some of its most stringent lockdown measures. Subsequent data from China's health authorities revealed that 248 million people, nearly 18 percent of its population, had been infected in the first 20 days of that month. On 29 December, the US joined Italy, Japan, Taiwan and India in requiring negative COVID-19 test results from all people traveling from China due to the new surge in cases. The EU refused similar measures, stating that the BF7 omicron variant had already spread throughout Europe without becoming dominant. On 4 January 2023, the World Health Organization said the information shared by China during the recent surge in infections lacked data, such as hospitalization rates. On 10 January, the WHO's Europe office said the recent viral surge in China posed "no immediate threat." On 16 January, the WHO recommended that China monitor excess mortality to provide "a more comprehensive understanding of the impact of COVID-19." On 30 January, the three-year anniversary of the original declaration, the World Health Organization determined that COVID-19 still met the criteria for a public health emergency of international concern (PHEIC). On 19 March, WHO Director-General Tedros indicated he was "confident" the COVID-19 pandemic would cease to be a public health emergency by the end of the year. On 5 May, the WHO downgraded COVID-19 from being a global health emergency, though it continued to refer to it as a pandemic. The WHO does not make official declarations of when pandemics end. The decision came after Tedros convened with the International Health Regulations Emergency Committee, wherein the Committee noted that due to the decrease in deaths and hospitalisations, and the prevalence of vaccinations and the level of general immunity, it was time to remove the emergency designation and "transition to long-term management". Tedros agreed, and the WHO reduced the classification to an "established and ongoing health issue". In a press conference, Tedros remarked that the diminishing threat from COVID-19 had "allowed most countries to return to life as we knew it before COVID-19". In September the WHO said it had observed "concerning" trends in COVID-19 case numbers and hospitalisations, although analysis was hampered because many countries were no longer recording COVID-19 case statistics. In November 2023, in response to viral mutations and changing characteristics of infection, the WHO adjusted its treatment guidelines. Among other changes, remdesivir and molnupiravir were now recommended only for the most severe cases, and deuremidevir and ivermectin were recommended against. National reactions ranged from strict lockdowns to public education campaigns. WHO recommended that curfews and lockdowns should be short-term measures to reorganise, regroup, rebalance resources, and protect the health care system. As of 26 March 2020, 1.7 billion people worldwide were under some form of lockdown. This increased to 3.9 billion people by the first week of April—more than half the world's population . In several countries, protests rose against restrictions such as lockdowns. A February 2021 study found that protests against restrictions were likely to directly increase the spread of the virus. As of the end of 2021, Asia's peak had come at the same time and at the same level as the world as a whole, in May 2021. However, cumulatively they had experienced only half of the global average in cases. China opted for containment, instituting strict lockdowns to eliminate viral spread. The vaccines distributed in China included the BIBP , WIBP , and CoronaVac . It was reported on 11 December 2021, that China had vaccinated 1.162 billion of its citizens, or 82.5% of the total population of the country against COVID-19. China's large-scale adoption of zero-COVID had largely contained the first waves of infections of the disease. When the waves of infections due to the Omicron variant followed, China was almost alone in pursuing the strategy of zero-Covid to combat the spread of the virus in 2022. Lockdown continued to be employed in November to combat a new wave of cases; however, protests erupted in cities across China over the country's stringent measures, and in December that year, the country relaxed its zero-COVID policy. On 20 December 2022, the Chinese State Council narrowed its definition of what would be counted as a COVID-19 death to include solely respiratory failure, which led to skepticism by health experts of the government's total death count at a time when hospitals reported being overwhelmed with cases following the abrupt discontinuation of zero-COVID. The first case in India was reported on 30 January 2020. India ordered a nationwide lockdown starting 24 March 2020, with a phased unlock beginning 1 June 2020. Six cities accounted for around half of reported cases— Mumbai , Delhi , Ahmedabad , Chennai , Pune and Kolkata . Post-lockdown, the Government of India introduced a contact tracking app called Aarogya Setu to help authorities manage contact tracing and vaccine distribution. India's vaccination program was considered to be the world's largest and most successful with over 90% of citizens getting the first dose and another 65% getting the second dose. A second wave hit India in April 2021, straining healthcare services. On 21 October 2021, it was reported that the country had surpassed 1 billion vaccinations. Iran reported its first confirmed cases on 19 February 2020, in Qom . Early measures included the cancellation/closure of concerts and other cultural events, Friday prayers, and school and university campuses. Iran became a centre of the pandemic in February 2020. More than ten countries had traced their outbreaks to Iran by 28 February, indicating a more severe outbreak than the 388 reported cases. The Iranian Parliament closed, after 23 of its 290 members tested positive on 3 March 2020. At least twelve sitting or former Iranian politicians and government officials had died by 17 March 2020. By August 2021, the pandemic's fifth wave peaked, with more than 400 deaths in 1 day. COVID-19 was confirmed in South Korea on 20 January 2020. Military bases were quarantined after tests showed three infected soldiers. South Korea introduced what was then considered the world's largest and best-organised screening programme, isolating infected people, and tracing and quarantining contacts. Screening methods included mandatory self-reporting by new international arrivals through mobile application, combined with drive-through testing, and increasing testing capability to 20,000 people/day. Despite some early criticisms, South Korea's programme was considered a success in controlling the outbreak without quarantining entire cities. The COVID-19 pandemic arrived in Europe with its first confirmed case in Bordeaux , France , on 24 January 2020, and subsequently spread widely across the continent. By 17 March 2020, every country in Europe had confirmed a case, and all had reported at least one death, with the exception of Vatican City . Italy was the first European nation to experience a major outbreak in early 2020, becoming the first country worldwide to introduce a national lockdown . By 13 March 2020, the World Health Organization (WHO) declared Europe the epicentre of the pandemic and it remained so until the WHO announced it had been overtaken by South America on 22 May. By 18 March 2020, more than 250 million people were in lockdown in Europe. Despite deployment of COVID-19 vaccines , Europe became the pandemic's epicentre once again in late 2021. The Italian outbreak began on 31 January 2020, when two Chinese tourists tested positive for SARS-CoV-2 in Rome. Cases began to rise sharply, which prompted the government to suspend flights to and from China and declare a state of emergency. On 22 February 2020, the Council of Ministers announced a new decree-law to contain the outbreak, which quarantined more than 50,000 people in northern Italy. On 4 March, the Italian government ordered schools and universities closed as Italy reached a hundred deaths. Sport was suspended completely for at least one month. On 11 March, Italian Prime Minister Giuseppe Conte closed down nearly all commercial activity except supermarkets and pharmacies. On 19 April, the first wave ebbed, as 7-day deaths declined to 433. On 13 October, the Italian government again issued restrictive rules to contain the second wave. On 10 November, Italy surpassed 1 million confirmed infections. On 23 November, it was reported that the second wave of the virus had led some hospitals to stop accepting patients. The virus was first confirmed to have spread to Spain on 31 January 2020, when a German tourist tested positive for SARS-CoV-2 on La Gomera in the Canary Islands. Post-hoc genetic analysis has shown that at least 15 strains of the virus had been imported, and community transmission began by mid-February. On 29 March, it was announced that, beginning the following day, all non-essential workers were ordered to remain at home for the next 14 days. The number of cases increased again in July in a number of cities including Barcelona , Zaragoza and Madrid , which led to reimposition of some restrictions but no national lockdown. By September 2021, Spain was one of the countries with the highest percentage of its population vaccinated (76% fully vaccinated and 79% with the first dose). Italy is ranked second at 75%. Sweden differed from most other European countries in that it mostly remained open. Per the Swedish constitution , the Public Health Agency of Sweden has autonomy that prevents political interference and the agency favoured remaining open. The Swedish strategy focused on longer-term measures, based on the assumption that after lockdown the virus would resume spreading, with the same result. By the end of June, Sweden no longer had excess mortality . Devolution in the United Kingdom meant that each of its four countries developed its own response. England's restrictions were shorter-lived than the others. The UK government started enforcing social distancing and quarantine measures on 18 March 2020. On 16 March, Prime Minister Boris Johnson advised against non-essential travel and social contact, praising work from home and avoiding venues such as pubs, restaurants, and theatres. On 20 March, the government ordered all leisure establishments to close, and promised to prevent unemployment. On 23 March, Johnson banned gatherings and restricted non-essential travel and outdoor activity. Unlike previous measures, these restrictions were enforceable by police through fines and dispersal of gatherings. Most non-essential businesses were ordered to close. On 24 April 2020, it was reported that a promising vaccine trial had begun in England; the government pledged more than £50 million towards research. On 16 April 2020, it was reported that the UK would have first access to the Oxford vaccine, due to a prior contract; should the trial be successful, some 30 million doses would be available. On 2 December 2020, the UK became the first developed country to approve the Pfizer vaccine; 800,000 doses were immediately available for use. In August 2022 it was reported that viral infection cases had declined in the UK. The virus arrived in the United States on 13 January 2020. Cases were reported in all North American countries after Saint Kitts and Nevis confirmed a case on 25 March, and in all North American territories after Bonaire confirmed a case on 16 April. Per Our World in Data , 103,436,829 confirmed cases have been reported in the United States with 1,184,883 deaths, the most of any country, and the nineteenth-highest per capita worldwide. COVID-19 is the deadliest pandemic in US history ; it was the third-leading cause of death in the US in 2020, behind heart disease and cancer. From 2019 to 2020, US life expectancy dropped by 3 years for Hispanic Americans, 2.9 years for African Americans, and 1.2 years for white Americans. These effects have persisted as US deaths due to COVID-19 in 2021 exceeded those in 2020. In the United States, COVID-19 vaccines became available under emergency use in December 2020, beginning the national vaccination program . The first COVID-19 vaccine was officially approved by the Food and Drug Administration on 23 August 2021. By 18 November 2022, while cases in the U.S. had declined, COVID variants BQ.1/BQ.1.1 had become dominant in the country. In March 2020, as cases of community transmission were confirmed across Canada , all of its provinces and territories declared states of emergency. Provinces and territories, to varying degrees, implemented school and daycare closures, prohibitions on gatherings, closures of non-essential businesses and restrictions on entry. Canada severely restricted its border access, barring travellers from all countries with some exceptions. Cases surged across Canada, notably in the provinces of British Columbia , Alberta , Quebec and Ontario , with the formation of the Atlantic Bubble , a travel-restricted area of the country (formed of the four Atlantic provinces ). Vaccine passports were adopted in all provinces and two of the territories. Per a report on 11 November 2022, Canadian health authorities saw a surge in influenza, while COVID-19 was expected to rise during winter. The COVID-19 pandemic was confirmed to have reached South America on 26 February 2020, when Brazil confirmed a case in São Paulo . By 3 April, all countries and territories in South America had recorded at least one case. On 13 May 2020, it was reported that Latin America and the Caribbean had reported over 400,000 cases of COVID-19 infection with 23,091 deaths. On 22 May 2020, citing the rapid increase of infections in Brazil , the World Health Organization WHO declared South America the epicentre of the pandemic. As of 16 July 2021, South America had recorded 34,359,631 confirmed cases and 1,047,229 deaths from COVID-19. Due to a shortage of testing and medical facilities, it is believed that the outbreak is far larger than the official numbers show. The virus was confirmed to have spread to Brazil on 25 February 2020, when a man from São Paulo who had traveled to Italy tested positive for the virus. The disease had spread to every federative unit of Brazil by 21 March. On 19 June 2020, the country reported its one millionth case and nearly 49,000 reported deaths. One estimate of under-reporting was 22.62% of total reported COVID-19 mortality in 2020. As of 22 April 2024 , Brazil, with 37,519,960 confirmed cases and 702,116 deaths, has the third-highest number of confirmed cases and second-highest death toll from COVID-19 in the world, behind only those of the United States and India . The COVID-19 pandemic was confirmed to have spread to Africa on 14 February 2020, with the first confirmed case announced in Egypt . The first confirmed case in sub-Saharan Africa was announced in Nigeria at the end of February 2020. Within three months, the virus had spread throughout the continent; Lesotho , the last African sovereign state to have remained free of the virus, reported its first case on 13 May 2020. By 26 May, it appeared that most African countries were experiencing community transmission, although testing capacity was limited. Most of the identified imported cases arrived from Europe and the United States rather than from China where the virus originated. Many preventive measures were implemented by different countries in Africa including travel restrictions, flight cancellations, and event cancellations. Despite fears, Africa reported lower death rates than other, more economically developed regions. In early June 2021, Africa faced a third wave of COVID infections with cases rising in 14 countries. By 4 July the continent recorded more than 251,000 new COVID cases, a 20% increase from the prior week and a 12% increase from the January peak. More than sixteen African countries, including Malawi and Senegal , recorded an uptick in new cases. The World Health Organization labelled it Africa's 'Worst Pandemic Week Ever'. In October 2022, WHO reported that most countries on the African continent will miss the goal of 70 percent vaccination by the end of 2022. The COVID-19 pandemic was confirmed to have reached Oceania on 25 January 2020, with the first confirmed case reported in Melbourne , Australia . It has since spread elsewhere in the region. Australia and New Zealand were praised for their handling of the pandemic in comparison to other Western nations, with New Zealand and each state in Australia wiping out all community transmission of the virus several times even after re-introduction into the community. As a result of the high transmissibility of the Delta variant, however, by August 2021, the Australian states of New South Wales and Victoria had conceded defeat in their eradication efforts. In early October 2021, New Zealand also abandoned its elimination strategy. In November and December, following vaccination efforts, the remaining states of Australia, excluding Western Australia, voluntarily gave up COVID-zero to open up state and international borders. The open borders allowed the Omicron Variant of COVID-19 to enter quickly and cases subsequently exceeded 120,000 a day. By early March 2022, with cases exceeding 1,000 a day, Western Australia conceded defeat in its eradication strategy and opened its borders. Despite record cases, Australian jurisdictions slowly removed restrictions such as close contact isolation, mask wearing and density limits by April 2022. On 9 September 2022 restrictions were significantly relaxed. The aircraft mask mandate was scrapped nationwide and daily reporting transitioned to weekly reporting. On 14 September, COVID-19 disaster payment for isolating persons was extended for mandatory isolation. By 22 September, all states had ended mask mandates on public transport, including in Victoria, where the mandate had lasted for approximately 800 days. On 30 September 2022, all Australian leaders declared the emergency response finished and announced the end of isolation requirements. These changes were due in part to high levels of 'hybrid immunity' and low case numbers. Due to its remoteness and sparse population, Antarctica was the last continent to have confirmed cases of COVID-19. The first cases were reported in December 2020, almost a year after the first cases of COVID-19 were detected in China. At least 36 people were infected in the first outbreak in 2020, with several other outbreaks taking place in 2021 and 2022. The United Nations Conference on Trade and Development (UNSC) was criticised for its slow response, especially regarding the UN's global ceasefire , which aimed to open up humanitarian access to conflict zones. The United Nations Security Council was criticized due to the inadequate manner in which it dealt with the COVID-19 pandemic, namely the poor ability to create international collaboration during this crisis. On 23 March 2020, United Nations Secretary-General António Manuel de Oliveira Guterres appealed for a global ceasefire ; 172 UN member states and observers signed a non-binding supporting statement in June, and the UN Security Council passed a resolution supporting it in July. On 29 September 2020, Guterres urged the International Monetary Fund to help certain countries via debt relief and also call for countries to increase contributions to develop vaccines. The WHO spearheaded initiatives such as the COVID-19 Solidarity Response Fund to raise money for the pandemic response, the UN COVID-19 Supply Chain Task Force , and the solidarity trial for investigating potential treatment options for the disease. The COVAX program, co-led by the WHO, GAVI , and the Coalition for Epidemic Preparedness Innovations (CEPI), aimed to accelerate the development, manufacture, and distribution of COVID-19 vaccines, and to guarantee fair and equitable access across the world. As of the end of 2021, Asia's peak had come at the same time and at the same level as the world as a whole, in May 2021. However, cumulatively they had experienced only half of the global average in cases. China opted for containment, instituting strict lockdowns to eliminate viral spread. The vaccines distributed in China included the BIBP , WIBP , and CoronaVac . It was reported on 11 December 2021, that China had vaccinated 1.162 billion of its citizens, or 82.5% of the total population of the country against COVID-19. China's large-scale adoption of zero-COVID had largely contained the first waves of infections of the disease. When the waves of infections due to the Omicron variant followed, China was almost alone in pursuing the strategy of zero-Covid to combat the spread of the virus in 2022. Lockdown continued to be employed in November to combat a new wave of cases; however, protests erupted in cities across China over the country's stringent measures, and in December that year, the country relaxed its zero-COVID policy. On 20 December 2022, the Chinese State Council narrowed its definition of what would be counted as a COVID-19 death to include solely respiratory failure, which led to skepticism by health experts of the government's total death count at a time when hospitals reported being overwhelmed with cases following the abrupt discontinuation of zero-COVID. The first case in India was reported on 30 January 2020. India ordered a nationwide lockdown starting 24 March 2020, with a phased unlock beginning 1 June 2020. Six cities accounted for around half of reported cases— Mumbai , Delhi , Ahmedabad , Chennai , Pune and Kolkata . Post-lockdown, the Government of India introduced a contact tracking app called Aarogya Setu to help authorities manage contact tracing and vaccine distribution. India's vaccination program was considered to be the world's largest and most successful with over 90% of citizens getting the first dose and another 65% getting the second dose. A second wave hit India in April 2021, straining healthcare services. On 21 October 2021, it was reported that the country had surpassed 1 billion vaccinations. Iran reported its first confirmed cases on 19 February 2020, in Qom . Early measures included the cancellation/closure of concerts and other cultural events, Friday prayers, and school and university campuses. Iran became a centre of the pandemic in February 2020. More than ten countries had traced their outbreaks to Iran by 28 February, indicating a more severe outbreak than the 388 reported cases. The Iranian Parliament closed, after 23 of its 290 members tested positive on 3 March 2020. At least twelve sitting or former Iranian politicians and government officials had died by 17 March 2020. By August 2021, the pandemic's fifth wave peaked, with more than 400 deaths in 1 day. COVID-19 was confirmed in South Korea on 20 January 2020. Military bases were quarantined after tests showed three infected soldiers. South Korea introduced what was then considered the world's largest and best-organised screening programme, isolating infected people, and tracing and quarantining contacts. Screening methods included mandatory self-reporting by new international arrivals through mobile application, combined with drive-through testing, and increasing testing capability to 20,000 people/day. Despite some early criticisms, South Korea's programme was considered a success in controlling the outbreak without quarantining entire cities. The COVID-19 pandemic arrived in Europe with its first confirmed case in Bordeaux , France , on 24 January 2020, and subsequently spread widely across the continent. By 17 March 2020, every country in Europe had confirmed a case, and all had reported at least one death, with the exception of Vatican City . Italy was the first European nation to experience a major outbreak in early 2020, becoming the first country worldwide to introduce a national lockdown . By 13 March 2020, the World Health Organization (WHO) declared Europe the epicentre of the pandemic and it remained so until the WHO announced it had been overtaken by South America on 22 May. By 18 March 2020, more than 250 million people were in lockdown in Europe. Despite deployment of COVID-19 vaccines , Europe became the pandemic's epicentre once again in late 2021. The Italian outbreak began on 31 January 2020, when two Chinese tourists tested positive for SARS-CoV-2 in Rome. Cases began to rise sharply, which prompted the government to suspend flights to and from China and declare a state of emergency. On 22 February 2020, the Council of Ministers announced a new decree-law to contain the outbreak, which quarantined more than 50,000 people in northern Italy. On 4 March, the Italian government ordered schools and universities closed as Italy reached a hundred deaths. Sport was suspended completely for at least one month. On 11 March, Italian Prime Minister Giuseppe Conte closed down nearly all commercial activity except supermarkets and pharmacies. On 19 April, the first wave ebbed, as 7-day deaths declined to 433. On 13 October, the Italian government again issued restrictive rules to contain the second wave. On 10 November, Italy surpassed 1 million confirmed infections. On 23 November, it was reported that the second wave of the virus had led some hospitals to stop accepting patients. The virus was first confirmed to have spread to Spain on 31 January 2020, when a German tourist tested positive for SARS-CoV-2 on La Gomera in the Canary Islands. Post-hoc genetic analysis has shown that at least 15 strains of the virus had been imported, and community transmission began by mid-February. On 29 March, it was announced that, beginning the following day, all non-essential workers were ordered to remain at home for the next 14 days. The number of cases increased again in July in a number of cities including Barcelona , Zaragoza and Madrid , which led to reimposition of some restrictions but no national lockdown. By September 2021, Spain was one of the countries with the highest percentage of its population vaccinated (76% fully vaccinated and 79% with the first dose). Italy is ranked second at 75%. Sweden differed from most other European countries in that it mostly remained open. Per the Swedish constitution , the Public Health Agency of Sweden has autonomy that prevents political interference and the agency favoured remaining open. The Swedish strategy focused on longer-term measures, based on the assumption that after lockdown the virus would resume spreading, with the same result. By the end of June, Sweden no longer had excess mortality . Devolution in the United Kingdom meant that each of its four countries developed its own response. England's restrictions were shorter-lived than the others. The UK government started enforcing social distancing and quarantine measures on 18 March 2020. On 16 March, Prime Minister Boris Johnson advised against non-essential travel and social contact, praising work from home and avoiding venues such as pubs, restaurants, and theatres. On 20 March, the government ordered all leisure establishments to close, and promised to prevent unemployment. On 23 March, Johnson banned gatherings and restricted non-essential travel and outdoor activity. Unlike previous measures, these restrictions were enforceable by police through fines and dispersal of gatherings. Most non-essential businesses were ordered to close. On 24 April 2020, it was reported that a promising vaccine trial had begun in England; the government pledged more than £50 million towards research. On 16 April 2020, it was reported that the UK would have first access to the Oxford vaccine, due to a prior contract; should the trial be successful, some 30 million doses would be available. On 2 December 2020, the UK became the first developed country to approve the Pfizer vaccine; 800,000 doses were immediately available for use. In August 2022 it was reported that viral infection cases had declined in the UK. The virus arrived in the United States on 13 January 2020. Cases were reported in all North American countries after Saint Kitts and Nevis confirmed a case on 25 March, and in all North American territories after Bonaire confirmed a case on 16 April. Per Our World in Data , 103,436,829 confirmed cases have been reported in the United States with 1,184,883 deaths, the most of any country, and the nineteenth-highest per capita worldwide. COVID-19 is the deadliest pandemic in US history ; it was the third-leading cause of death in the US in 2020, behind heart disease and cancer. From 2019 to 2020, US life expectancy dropped by 3 years for Hispanic Americans, 2.9 years for African Americans, and 1.2 years for white Americans. These effects have persisted as US deaths due to COVID-19 in 2021 exceeded those in 2020. In the United States, COVID-19 vaccines became available under emergency use in December 2020, beginning the national vaccination program . The first COVID-19 vaccine was officially approved by the Food and Drug Administration on 23 August 2021. By 18 November 2022, while cases in the U.S. had declined, COVID variants BQ.1/BQ.1.1 had become dominant in the country. In March 2020, as cases of community transmission were confirmed across Canada , all of its provinces and territories declared states of emergency. Provinces and territories, to varying degrees, implemented school and daycare closures, prohibitions on gatherings, closures of non-essential businesses and restrictions on entry. Canada severely restricted its border access, barring travellers from all countries with some exceptions. Cases surged across Canada, notably in the provinces of British Columbia , Alberta , Quebec and Ontario , with the formation of the Atlantic Bubble , a travel-restricted area of the country (formed of the four Atlantic provinces ). Vaccine passports were adopted in all provinces and two of the territories. Per a report on 11 November 2022, Canadian health authorities saw a surge in influenza, while COVID-19 was expected to rise during winter. The COVID-19 pandemic was confirmed to have reached South America on 26 February 2020, when Brazil confirmed a case in São Paulo . By 3 April, all countries and territories in South America had recorded at least one case. On 13 May 2020, it was reported that Latin America and the Caribbean had reported over 400,000 cases of COVID-19 infection with 23,091 deaths. On 22 May 2020, citing the rapid increase of infections in Brazil , the World Health Organization WHO declared South America the epicentre of the pandemic. As of 16 July 2021, South America had recorded 34,359,631 confirmed cases and 1,047,229 deaths from COVID-19. Due to a shortage of testing and medical facilities, it is believed that the outbreak is far larger than the official numbers show. The virus was confirmed to have spread to Brazil on 25 February 2020, when a man from São Paulo who had traveled to Italy tested positive for the virus. The disease had spread to every federative unit of Brazil by 21 March. On 19 June 2020, the country reported its one millionth case and nearly 49,000 reported deaths. One estimate of under-reporting was 22.62% of total reported COVID-19 mortality in 2020. As of 22 April 2024 , Brazil, with 37,519,960 confirmed cases and 702,116 deaths, has the third-highest number of confirmed cases and second-highest death toll from COVID-19 in the world, behind only those of the United States and India . The COVID-19 pandemic was confirmed to have spread to Africa on 14 February 2020, with the first confirmed case announced in Egypt . The first confirmed case in sub-Saharan Africa was announced in Nigeria at the end of February 2020. Within three months, the virus had spread throughout the continent; Lesotho , the last African sovereign state to have remained free of the virus, reported its first case on 13 May 2020. By 26 May, it appeared that most African countries were experiencing community transmission, although testing capacity was limited. Most of the identified imported cases arrived from Europe and the United States rather than from China where the virus originated. Many preventive measures were implemented by different countries in Africa including travel restrictions, flight cancellations, and event cancellations. Despite fears, Africa reported lower death rates than other, more economically developed regions. In early June 2021, Africa faced a third wave of COVID infections with cases rising in 14 countries. By 4 July the continent recorded more than 251,000 new COVID cases, a 20% increase from the prior week and a 12% increase from the January peak. More than sixteen African countries, including Malawi and Senegal , recorded an uptick in new cases. The World Health Organization labelled it Africa's 'Worst Pandemic Week Ever'. In October 2022, WHO reported that most countries on the African continent will miss the goal of 70 percent vaccination by the end of 2022. The COVID-19 pandemic was confirmed to have reached Oceania on 25 January 2020, with the first confirmed case reported in Melbourne , Australia . It has since spread elsewhere in the region. Australia and New Zealand were praised for their handling of the pandemic in comparison to other Western nations, with New Zealand and each state in Australia wiping out all community transmission of the virus several times even after re-introduction into the community. As a result of the high transmissibility of the Delta variant, however, by August 2021, the Australian states of New South Wales and Victoria had conceded defeat in their eradication efforts. In early October 2021, New Zealand also abandoned its elimination strategy. In November and December, following vaccination efforts, the remaining states of Australia, excluding Western Australia, voluntarily gave up COVID-zero to open up state and international borders. The open borders allowed the Omicron Variant of COVID-19 to enter quickly and cases subsequently exceeded 120,000 a day. By early March 2022, with cases exceeding 1,000 a day, Western Australia conceded defeat in its eradication strategy and opened its borders. Despite record cases, Australian jurisdictions slowly removed restrictions such as close contact isolation, mask wearing and density limits by April 2022. On 9 September 2022 restrictions were significantly relaxed. The aircraft mask mandate was scrapped nationwide and daily reporting transitioned to weekly reporting. On 14 September, COVID-19 disaster payment for isolating persons was extended for mandatory isolation. By 22 September, all states had ended mask mandates on public transport, including in Victoria, where the mandate had lasted for approximately 800 days. On 30 September 2022, all Australian leaders declared the emergency response finished and announced the end of isolation requirements. These changes were due in part to high levels of 'hybrid immunity' and low case numbers. Due to its remoteness and sparse population, Antarctica was the last continent to have confirmed cases of COVID-19. The first cases were reported in December 2020, almost a year after the first cases of COVID-19 were detected in China. At least 36 people were infected in the first outbreak in 2020, with several other outbreaks taking place in 2021 and 2022. The United Nations Conference on Trade and Development (UNSC) was criticised for its slow response, especially regarding the UN's global ceasefire , which aimed to open up humanitarian access to conflict zones. The United Nations Security Council was criticized due to the inadequate manner in which it dealt with the COVID-19 pandemic, namely the poor ability to create international collaboration during this crisis. On 23 March 2020, United Nations Secretary-General António Manuel de Oliveira Guterres appealed for a global ceasefire ; 172 UN member states and observers signed a non-binding supporting statement in June, and the UN Security Council passed a resolution supporting it in July. On 29 September 2020, Guterres urged the International Monetary Fund to help certain countries via debt relief and also call for countries to increase contributions to develop vaccines. The WHO spearheaded initiatives such as the COVID-19 Solidarity Response Fund to raise money for the pandemic response, the UN COVID-19 Supply Chain Task Force , and the solidarity trial for investigating potential treatment options for the disease. The COVAX program, co-led by the WHO, GAVI , and the Coalition for Epidemic Preparedness Innovations (CEPI), aimed to accelerate the development, manufacture, and distribution of COVID-19 vaccines, and to guarantee fair and equitable access across the world. The pandemic shook the world's economy, with especially severe economic damage in the United States, Europe and Latin America. A consensus report by American intelligence agencies in April 2021 concluded, "Efforts to contain and manage the virus have reinforced nationalist trends globally, as some states turned inward to protect their citizens and sometimes cast blame on marginalized groups." COVID-19 inflamed partisanship and polarisation around the world as bitter arguments exploded over how to respond. International trade was disrupted amid the formation of no-entry enclaves. The pandemic led many countries and regions to impose quarantines, entry bans, or other restrictions, either for citizens, recent travellers to affected areas, or for all travellers. Travel collapsed worldwide, damaging the travel sector. The effectiveness of travel restrictions was questioned as the virus spread across the world. One study found that travel restrictions only modestly affected the initial spread, unless combined with other infection prevention and control measures. Researchers concluded that "travel restrictions are most useful in the early and late phase of an epidemic" and "restrictions of travel from Wuhan unfortunately came too late". The European Union rejected the idea of suspending the Schengen free travel zone . Several countries repatriated their citizens and diplomatic staff from Wuhan and surrounding areas, primarily through charter flights . Canada, the United States, Japan, India, Sri Lanka, Australia, France, Argentina, Germany and Thailand were among the first to do so. Brazil and New Zealand evacuated their own nationals and others. On 14 March, South Africa repatriated 112 South Africans who tested negative, while four who showed symptoms were left behind. Pakistan declined to evacuate its citizens. On 15 February, the US announced it would evacuate Americans aboard the Diamond Princess cruise ship, and on 21 February, Canada evacuated 129 Canadians from the ship. In early March, the Indian government began repatriating its citizens from Iran. On 20 March, the United States began to withdraw some troops from Iraq. The pandemic led many countries and regions to impose quarantines, entry bans, or other restrictions, either for citizens, recent travellers to affected areas, or for all travellers. Travel collapsed worldwide, damaging the travel sector. The effectiveness of travel restrictions was questioned as the virus spread across the world. One study found that travel restrictions only modestly affected the initial spread, unless combined with other infection prevention and control measures. Researchers concluded that "travel restrictions are most useful in the early and late phase of an epidemic" and "restrictions of travel from Wuhan unfortunately came too late". The European Union rejected the idea of suspending the Schengen free travel zone . Several countries repatriated their citizens and diplomatic staff from Wuhan and surrounding areas, primarily through charter flights . Canada, the United States, Japan, India, Sri Lanka, Australia, France, Argentina, Germany and Thailand were among the first to do so. Brazil and New Zealand evacuated their own nationals and others. On 14 March, South Africa repatriated 112 South Africans who tested negative, while four who showed symptoms were left behind. Pakistan declined to evacuate its citizens. On 15 February, the US announced it would evacuate Americans aboard the Diamond Princess cruise ship, and on 21 February, Canada evacuated 129 Canadians from the ship. In early March, the Indian government began repatriating its citizens from Iran. On 20 March, the United States began to withdraw some troops from Iraq. The pandemic and responses to it damaged the global economy. On 27 February 2020, worries about the outbreak crushed US stock indexes, which posted their sharpest falls since 2008. Tourism collapsed due to travel restrictions, closing of public places including travel attractions, and advice of governments against travel. Airlines cancelled flights, while British regional airline Flybe collapsed. The cruise line industry was hard hit, and train stations and ferry ports closed. International mail stopped or was delayed. The retail sector faced reductions in store hours or closures. Retailers in Europe and Latin America faced traffic declines of 40 percent. North America and Middle East retailers saw a 50–60 percent drop. Shopping centres faced a 33–43 percent drop in foot traffic in March compared to February. Mall operators around the world coped by increasing sanitation, installing thermal scanners to check the temperature of shoppers, and cancelling events. Hundreds of millions of jobs were lost, including more than 40 million jobs in the US. According to a report by Yelp , about 60% of US businesses that closed will stay shut permanently. The International Labour Organization (ILO) reported that the income generated in the first nine months of 2020 from work across the world dropped by 10.7 percent, or $3.5 trillion. Pandemic fears led to panic buying , emptying groceries of essentials such as food, toilet paper, and bottled water. Panic buying stemmed from perceived threat, perceived scarcity, fear of the unknown, coping behaviour and social psychological factors (e.g. social influence and trust). Supply shortages were due to disruption to factory and logistic operations; shortages were worsened by supply chain disruptions from factory and port shutdowns, and labour shortages. Shortages continued as managers underestimated the speed of economic recovery after the initial economic crash. The technology industry, in particular, warned of delays from underestimates of semiconductor demand for vehicles and other products. According to WHO Secretary-General Tedros Ghebreyesus, demand for personal protective equipment (PPE) rose one hundredfold, pushing prices up twentyfold. PPE stocks were exhausted everywhere. In September 2021, the World Bank reported that food prices remained generally stable and the supply outlook remained positive. However, the poorest countries witnessed a sharp increase in food prices, reaching the highest level since the pandemic began. The Agricultural Commodity Price Index stabilized in the third quarter but remained 17% higher than in January 2021. By contrast, petroleum products were in surplus at the beginning of the pandemic, as demand for gasoline and other products collapsed due to reduced commuting and other trips. The 2021 global energy crisis was driven by a global surge in demand as the world economy recovered. Energy demand was particularly strong in Asia. The performing arts and cultural heritage sectors were profoundly affected by the pandemic. Both organisations' and individuals' operations have been impacted globally. By March 2020, across the world and to varying degrees, museums, libraries, performance venues, and other cultural institutions had been indefinitely closed with their exhibitions, events and performances cancelled or postponed. A 2021 UNESCO report estimated ten million job losses worldwide in the culture and creative industries. Some services continued through digital platforms, such as live streaming concerts or web-based arts festivals. The pandemic affected political systems, causing suspensions of legislative activities, isolations or deaths of politicians, and rescheduled elections. Although they developed broad support among epidemiologists, NPIs (non-pharmaceutical interventions) were controversial in many countries. Intellectual opposition came primarily from other fields, along with heterodox epidemiologists. The pandemic (and the response of Brazilian politicians to it) led to widespread panic, confusion, and pessimism in Brazil. When questioned regarding record deaths in the country in April 2020, Brazilian President Jair Bolsonaro said "So what? I'm sorry. What do you want me to do about it?" Bolsonaro disregarded WHO-recommended mitigation techniques and instead downplayed the risks of the virus , promoted increased economic activity, spread misinformation about the efficacy of masks, vaccines and public health measures, and distributed unproven treatments including hydroxychloroquine and ivermectin . A series of federal health ministers resigned or were dismissed after they refused to implement Bolsonaro's policies. Disagreements between federal and state governments led to a chaotic and delayed response to the rapid spread of the virus, exacerbated by preexisting social and economic disparities in the country. Employment, investment and valuation of the Brazilian real plummeted to record lows. Brazil was also heavily affected by the Delta and Omicron variants. At the height of the outbreak in the spring of 2021, 3,000+ Brazilians were dying per day. Bolsonaro's loss to Lula da Silva in the 2022 presidential election is widely credited to the former's mishandling of the pandemic . Multiple provincial-level administrators of the Chinese Communist Party (CCP) were dismissed over their handling of quarantine measures. Some commentators claimed this move was intended to protect CCP General Secretary Xi Jinping . The US intelligence community claimed that China intentionally under-reported its COVID-19 caseload. The Chinese government maintained that it acted swiftly and transparently. Journalists and activists in China who reported on the pandemic were detained by authorities, including Zhang Zhan , who was arrested and tortured. In early March 2020, the Italian government criticised the EU's lack of solidarity with Italy. On 22 March 2020, after a phone call with Italian Prime Minister Giuseppe Conte , Russian President Vladimir Putin ordered the Russian army to send military medics, disinfection vehicles, and other medical equipment to Italy. In early April, Norway and EU states like Romania and Austria started to offer help by sending medical personnel and disinfectant, and European Commission President Ursula von der Leyen offered an official apology to the country . Beginning in mid-April 2020, protestors objected to government-imposed business closures and restrictions on personal movement and assembly. Simultaneously, essential workers protested unsafe conditions and low wages by participating in a brief general strike . Some political analysts claimed that the pandemic contributed to President Donald Trump 's 2020 defeat. The COVID-19 pandemic in the United States prompted calls for the United States to adopt social policies common in other wealthy countries, including universal health care , universal child care , paid sick leave , and higher levels of funding for public health. The Kaiser Family Foundation estimated that preventable hospitalizations of unvaccinated Americans in the second half of 2021 cost US$13.8 billion. There were also protest in regards to vaccine mandates in the United States. In January 2022, the US Supreme Court struck down an OSHA rule that mandated vaccination or a testing regimen for all companies with greater than 100 employees. The number of journalists imprisoned or detained increased worldwide; some detentions were related to the pandemic. The planned NATO " Defender 2020 " military exercise in Germany, Poland and the Baltic states , the largest NATO war exercise since the end of the Cold War , was held on a reduced scale. The Iranian government was heavily affected by the virus, which infected some two dozen parliament members and political figures. Iran President Hassan Rouhani wrote a public letter to world leaders asking for help on 14 March 2020, due to a lack of access to international markets. Saudi Arabia, which had launched a military intervention in Yemen in March 2015, declared a ceasefire. Diplomatic relations between Japan and South Korea worsened. South Korea criticised Japan's "ambiguous and passive quarantine efforts" after Japan announced travellers from South Korea must quarantine for two weeks. South Korean society was initially polarised on President Moon Jae-in 's response to the crisis; many Koreans signed petitions calling for Moon's impeachment or praising his response. Some countries passed emergency legislation. Some commentators expressed concern that it could allow governments to strengthen their grip on power. In Hungary, the parliament voted to allow Prime Minister Viktor Orbán to rule by decree indefinitely, suspend parliament and elections, and punish those deemed to have spread false information. In countries such as Egypt , Turkey , and Thailand , opposition activists and government critics were arrested for allegedly spreading fake news . In India, journalists criticising the government's response were arrested or issued warnings by police and authorities. The pandemic disrupted food systems worldwide, hitting at a time when hunger and undernourishment were rising- an estimated 690 million people lacked food security in 2019. Food access fell – driven by falling incomes, lost remittances, and disruptions to food production. In some cases, food prices rose. The pandemic and its accompanying lockdowns and travel restrictions slowed movement of food aid. According to the WHO, 811 million people were undernourished in 2020, "likely related to the fallout of COVID-19". The pandemic impacted educational systems in many countries. Many governments temporarily closed educational institutions, often replaced by online education . Other countries, such as Sweden, kept their schools open. As of September 2020, approximately 1.077 billion learners were affected due to school closures. School closures impacted students, teachers, and families with far-reaching economic and societal consequences. They shed light on social and economic issues, including student debt , digital learning , food insecurity, and homelessness , as well as access to childcare , health care, housing, internet, and disability services . The impact was more severe for disadvantaged children. The Higher Education Policy Institute reported that around 63% of students claimed worsened mental health as a result of the pandemic. The pandemic impacted global health for many conditions. Hospital visits fell. Visits for heart attack symptoms declined by 38% in the US and 40% in Spain. The head of cardiology at the University of Arizona said, "My worry is some of these people are dying at home because they're too scared to go to the hospital." People with strokes and appendicitis were less likely to seek treatment. Medical supply shortages impacted many people. The pandemic impacted mental health , increasing anxiety , depression, and post-traumatic stress disorder , affecting healthcare workers, patients and quarantined individuals. In late 2022, during the first northern hemisphere autumn and winter seasons following the widespread relaxation of global public health measures, North America and Europe experienced a surge in respiratory viruses and coinfections in both adults and children. This formed the beginnings of the 2022–2023 pediatric care crisis and what some experts have termed a " tripledemic " of seasonal influenza, Respiratory Syncytial Virus (RSV) , and SARS-CoV-2 throughout North America. In the United Kingdom, pediatric infections also began to spike beyond pre-pandemic levels, albeit with different illnesses, such as Group A streptococcal infection and resultant scarlet fever . As of mid-December 2022, 19 children in the UK had died due to Strep A and the wave of infections had begun to spread into North America and Mainland Europe. The B/Yamagata lineage of influenza B might have become extinct in 2020/2021 due to COVID-19 pandemic measures. There have been no naturally occurring cases confirmed since March 2020. In 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. The pandemic and the reaction to it positively affected the environment and climate as a result of reduced human activity. During the " anthropause ", fossil fuel use decreased, resource consumption declined, and waste disposal improved, generating less pollution. Planned air travel and vehicle transportation declined. In China, lockdowns and other measures resulted in a 26% decrease in coal consumption, and a 50% reduction in nitrogen oxides emissions. In 2020, a worldwide study on mammalian wildlife responses to human presence during COVID lockdowns found complex patterns of animal behavior. Carnivores were generally less active when humans were around, while herbivores in developed areas were more active. Among other findings, this suggested that herbivores may view humans as a shield against predators, highlighting the importance of location and human presence history in understanding wildlife responses to changes in human activity in a given area. A wide variety of largely mammalian species, both captive and wild, have been shown to be susceptible to SARS-CoV-2, with some encountering a particularly high degree of fatal outcomes. In particular, both farmed and wild mink have developed highly symptomatic and severe COVID-19 infections, with a mortality rate as high as 35–55% according to one study. White-tailed deer , on the other hand, have largely avoided severe outcomes but have effectively become natural reservoirs of the virus, with large numbers of free-ranging deer infected throughout the US and Canada, including approximately 80% of Iowa 's wild deer herd. An August 2023 study appeared to confirm the status of white-tailed deer as a disease reservoir, noting that the viral evolution of SARS-CoV-2 in deer occurs at triple the rate of its evolution in humans and that infection rates remained high, even in areas rarely frequented by humans. Heightened prejudice, xenophobia , and racism toward people of Chinese and East Asian descent were documented around the world. Reports from February 2020, when most confirmed cases were confined to China, cited racist sentiments about Chinese people 'deserving' the virus. Individuals of Asian descent in Europe and North America reported increasing instances of racially-motivated abuse and assaults as a result of the pandemic. US President Donald Trump was criticised for referring to SARS-CoV-2 as the "Chinese Virus" and "Kung Flu", terms which were condemned as being racist and xenophobic. Age-based discrimination against older adults increased during the pandemic. This was attributed to their perceived vulnerability and subsequent physical and social isolation measures, which, coupled with their reduced social activity, increased dependency on others. Similarly, limited digital literacy left the elderly more vulnerable to isolation, depression, and loneliness. In a correspondence published in The Lancet in 2021, German epidemiologist Günter Kampf described the harmful effects of "inappropriate stigmatisation of unvaccinated people, who include our patients, colleagues, and other fellow citizens", noting the evidence that vaccinated individuals play a large role in transmission. American bioethicist Arthur Caplan responded to Kampf, writing "Criticising [the unvaccinated] who... wind up in hospitals and morgues in huge numbers, put stress on finite resources, and prolong the pandemic... is not stigmatising, it is deserved moral condemnation." In January 2022, Amnesty International urged Italy to change their anti-COVID-19 restrictions to avoid discrimination against unvaccinated people, saying that "the government must continue to ensure that the entire population can enjoy its fundamental rights." The restrictions included mandatory vaccination over the age of 50, and mandatory vaccination to use public transport. The pandemic triggered massive changes in behaviour, from increased Internet commerce to cultural changes in the workplace. Online retailers in the US posted $791.70 billion in sales in 2020, an increase of 32.4% from $598.02 billion the year before. Home delivery orders increased, while indoor restaurant dining shut down due to lockdown orders or low sales. Hackers, cybercriminals and scammers took advantage of the changes to launch new online attacks. Education in some countries temporarily shifted from physical attendance to video conferencing. Massive layoffs shrank the airline, travel, hospitality, and other industries. Despite most corporations implementing measures to address COVID-19 in the workplace, a poll from Catalyst found that as many as 68% of employees around the world felt that these policies were only performative and "not genuine". The pandemic led to a surge in remote work . According to a Gallup poll , only 4% of US employees were fully remote before the pandemic, compared to 43% in May 2020. Among white collar workers, that shift was more pronounced, with 6% increasing to 65% in the same period. That trend continued in later stages of the pandemic, with many workers choosing to remain remote even after workplaces reopened. Many Nordic, European, and Asian companies increased their recruitment of international remote workers even as the pandemic waned, partially to save on labor costs. This also led to a talent drain in the global south and in remote areas in the global north. High cost of living and dense urban areas also lost office real estate value due to remote worker exodus. By May 2023, due to increasing layoffs and concerns over productivity, some white collar workplaces in the US had resorted to performance review penalties and indirect incentives (e.g. donations to charity) to encourage workers to return to the office. A 2021 study noted that the COVID-19 pandemic had increased interest in epidemics and infectious diseases among both historians and the general public. Prior to the pandemic, these topics were usually overlooked by "general" history and only received attention in the history of medicine . Many comparisons were made between the COVID-19 and 1918 influenza pandemics , including the development of anti-mask movements, the widespread promotion of misinformation and the impact of socioeconomic disparities . In some areas, religious groups exacerbated the spread of the virus, through large gatherings and the dissemination of misinformation. Some religious leaders decried what they saw as violations of religious freedom. In other cases, religious identity was a beneficial factor for health, increasing compliance with public health measures and protecting against the negative effects of isolation on mental wellbeing. The pandemic and responses to it damaged the global economy. On 27 February 2020, worries about the outbreak crushed US stock indexes, which posted their sharpest falls since 2008. Tourism collapsed due to travel restrictions, closing of public places including travel attractions, and advice of governments against travel. Airlines cancelled flights, while British regional airline Flybe collapsed. The cruise line industry was hard hit, and train stations and ferry ports closed. International mail stopped or was delayed. The retail sector faced reductions in store hours or closures. Retailers in Europe and Latin America faced traffic declines of 40 percent. North America and Middle East retailers saw a 50–60 percent drop. Shopping centres faced a 33–43 percent drop in foot traffic in March compared to February. Mall operators around the world coped by increasing sanitation, installing thermal scanners to check the temperature of shoppers, and cancelling events. Hundreds of millions of jobs were lost, including more than 40 million jobs in the US. According to a report by Yelp , about 60% of US businesses that closed will stay shut permanently. The International Labour Organization (ILO) reported that the income generated in the first nine months of 2020 from work across the world dropped by 10.7 percent, or $3.5 trillion. Pandemic fears led to panic buying , emptying groceries of essentials such as food, toilet paper, and bottled water. Panic buying stemmed from perceived threat, perceived scarcity, fear of the unknown, coping behaviour and social psychological factors (e.g. social influence and trust). Supply shortages were due to disruption to factory and logistic operations; shortages were worsened by supply chain disruptions from factory and port shutdowns, and labour shortages. Shortages continued as managers underestimated the speed of economic recovery after the initial economic crash. The technology industry, in particular, warned of delays from underestimates of semiconductor demand for vehicles and other products. According to WHO Secretary-General Tedros Ghebreyesus, demand for personal protective equipment (PPE) rose one hundredfold, pushing prices up twentyfold. PPE stocks were exhausted everywhere. In September 2021, the World Bank reported that food prices remained generally stable and the supply outlook remained positive. However, the poorest countries witnessed a sharp increase in food prices, reaching the highest level since the pandemic began. The Agricultural Commodity Price Index stabilized in the third quarter but remained 17% higher than in January 2021. By contrast, petroleum products were in surplus at the beginning of the pandemic, as demand for gasoline and other products collapsed due to reduced commuting and other trips. The 2021 global energy crisis was driven by a global surge in demand as the world economy recovered. Energy demand was particularly strong in Asia. Pandemic fears led to panic buying , emptying groceries of essentials such as food, toilet paper, and bottled water. Panic buying stemmed from perceived threat, perceived scarcity, fear of the unknown, coping behaviour and social psychological factors (e.g. social influence and trust). Supply shortages were due to disruption to factory and logistic operations; shortages were worsened by supply chain disruptions from factory and port shutdowns, and labour shortages. Shortages continued as managers underestimated the speed of economic recovery after the initial economic crash. The technology industry, in particular, warned of delays from underestimates of semiconductor demand for vehicles and other products. According to WHO Secretary-General Tedros Ghebreyesus, demand for personal protective equipment (PPE) rose one hundredfold, pushing prices up twentyfold. PPE stocks were exhausted everywhere. In September 2021, the World Bank reported that food prices remained generally stable and the supply outlook remained positive. However, the poorest countries witnessed a sharp increase in food prices, reaching the highest level since the pandemic began. The Agricultural Commodity Price Index stabilized in the third quarter but remained 17% higher than in January 2021. By contrast, petroleum products were in surplus at the beginning of the pandemic, as demand for gasoline and other products collapsed due to reduced commuting and other trips. The 2021 global energy crisis was driven by a global surge in demand as the world economy recovered. Energy demand was particularly strong in Asia. The performing arts and cultural heritage sectors were profoundly affected by the pandemic. Both organisations' and individuals' operations have been impacted globally. By March 2020, across the world and to varying degrees, museums, libraries, performance venues, and other cultural institutions had been indefinitely closed with their exhibitions, events and performances cancelled or postponed. A 2021 UNESCO report estimated ten million job losses worldwide in the culture and creative industries. Some services continued through digital platforms, such as live streaming concerts or web-based arts festivals. The pandemic affected political systems, causing suspensions of legislative activities, isolations or deaths of politicians, and rescheduled elections. Although they developed broad support among epidemiologists, NPIs (non-pharmaceutical interventions) were controversial in many countries. Intellectual opposition came primarily from other fields, along with heterodox epidemiologists. The pandemic (and the response of Brazilian politicians to it) led to widespread panic, confusion, and pessimism in Brazil. When questioned regarding record deaths in the country in April 2020, Brazilian President Jair Bolsonaro said "So what? I'm sorry. What do you want me to do about it?" Bolsonaro disregarded WHO-recommended mitigation techniques and instead downplayed the risks of the virus , promoted increased economic activity, spread misinformation about the efficacy of masks, vaccines and public health measures, and distributed unproven treatments including hydroxychloroquine and ivermectin . A series of federal health ministers resigned or were dismissed after they refused to implement Bolsonaro's policies. Disagreements between federal and state governments led to a chaotic and delayed response to the rapid spread of the virus, exacerbated by preexisting social and economic disparities in the country. Employment, investment and valuation of the Brazilian real plummeted to record lows. Brazil was also heavily affected by the Delta and Omicron variants. At the height of the outbreak in the spring of 2021, 3,000+ Brazilians were dying per day. Bolsonaro's loss to Lula da Silva in the 2022 presidential election is widely credited to the former's mishandling of the pandemic . Multiple provincial-level administrators of the Chinese Communist Party (CCP) were dismissed over their handling of quarantine measures. Some commentators claimed this move was intended to protect CCP General Secretary Xi Jinping . The US intelligence community claimed that China intentionally under-reported its COVID-19 caseload. The Chinese government maintained that it acted swiftly and transparently. Journalists and activists in China who reported on the pandemic were detained by authorities, including Zhang Zhan , who was arrested and tortured. In early March 2020, the Italian government criticised the EU's lack of solidarity with Italy. On 22 March 2020, after a phone call with Italian Prime Minister Giuseppe Conte , Russian President Vladimir Putin ordered the Russian army to send military medics, disinfection vehicles, and other medical equipment to Italy. In early April, Norway and EU states like Romania and Austria started to offer help by sending medical personnel and disinfectant, and European Commission President Ursula von der Leyen offered an official apology to the country . Beginning in mid-April 2020, protestors objected to government-imposed business closures and restrictions on personal movement and assembly. Simultaneously, essential workers protested unsafe conditions and low wages by participating in a brief general strike . Some political analysts claimed that the pandemic contributed to President Donald Trump 's 2020 defeat. The COVID-19 pandemic in the United States prompted calls for the United States to adopt social policies common in other wealthy countries, including universal health care , universal child care , paid sick leave , and higher levels of funding for public health. The Kaiser Family Foundation estimated that preventable hospitalizations of unvaccinated Americans in the second half of 2021 cost US$13.8 billion. There were also protest in regards to vaccine mandates in the United States. In January 2022, the US Supreme Court struck down an OSHA rule that mandated vaccination or a testing regimen for all companies with greater than 100 employees. The number of journalists imprisoned or detained increased worldwide; some detentions were related to the pandemic. The planned NATO " Defender 2020 " military exercise in Germany, Poland and the Baltic states , the largest NATO war exercise since the end of the Cold War , was held on a reduced scale. The Iranian government was heavily affected by the virus, which infected some two dozen parliament members and political figures. Iran President Hassan Rouhani wrote a public letter to world leaders asking for help on 14 March 2020, due to a lack of access to international markets. Saudi Arabia, which had launched a military intervention in Yemen in March 2015, declared a ceasefire. Diplomatic relations between Japan and South Korea worsened. South Korea criticised Japan's "ambiguous and passive quarantine efforts" after Japan announced travellers from South Korea must quarantine for two weeks. South Korean society was initially polarised on President Moon Jae-in 's response to the crisis; many Koreans signed petitions calling for Moon's impeachment or praising his response. Some countries passed emergency legislation. Some commentators expressed concern that it could allow governments to strengthen their grip on power. In Hungary, the parliament voted to allow Prime Minister Viktor Orbán to rule by decree indefinitely, suspend parliament and elections, and punish those deemed to have spread false information. In countries such as Egypt , Turkey , and Thailand , opposition activists and government critics were arrested for allegedly spreading fake news . In India, journalists criticising the government's response were arrested or issued warnings by police and authorities. The pandemic (and the response of Brazilian politicians to it) led to widespread panic, confusion, and pessimism in Brazil. When questioned regarding record deaths in the country in April 2020, Brazilian President Jair Bolsonaro said "So what? I'm sorry. What do you want me to do about it?" Bolsonaro disregarded WHO-recommended mitigation techniques and instead downplayed the risks of the virus , promoted increased economic activity, spread misinformation about the efficacy of masks, vaccines and public health measures, and distributed unproven treatments including hydroxychloroquine and ivermectin . A series of federal health ministers resigned or were dismissed after they refused to implement Bolsonaro's policies. Disagreements between federal and state governments led to a chaotic and delayed response to the rapid spread of the virus, exacerbated by preexisting social and economic disparities in the country. Employment, investment and valuation of the Brazilian real plummeted to record lows. Brazil was also heavily affected by the Delta and Omicron variants. At the height of the outbreak in the spring of 2021, 3,000+ Brazilians were dying per day. Bolsonaro's loss to Lula da Silva in the 2022 presidential election is widely credited to the former's mishandling of the pandemic . Multiple provincial-level administrators of the Chinese Communist Party (CCP) were dismissed over their handling of quarantine measures. Some commentators claimed this move was intended to protect CCP General Secretary Xi Jinping . The US intelligence community claimed that China intentionally under-reported its COVID-19 caseload. The Chinese government maintained that it acted swiftly and transparently. Journalists and activists in China who reported on the pandemic were detained by authorities, including Zhang Zhan , who was arrested and tortured. In early March 2020, the Italian government criticised the EU's lack of solidarity with Italy. On 22 March 2020, after a phone call with Italian Prime Minister Giuseppe Conte , Russian President Vladimir Putin ordered the Russian army to send military medics, disinfection vehicles, and other medical equipment to Italy. In early April, Norway and EU states like Romania and Austria started to offer help by sending medical personnel and disinfectant, and European Commission President Ursula von der Leyen offered an official apology to the country . Beginning in mid-April 2020, protestors objected to government-imposed business closures and restrictions on personal movement and assembly. Simultaneously, essential workers protested unsafe conditions and low wages by participating in a brief general strike . Some political analysts claimed that the pandemic contributed to President Donald Trump 's 2020 defeat. The COVID-19 pandemic in the United States prompted calls for the United States to adopt social policies common in other wealthy countries, including universal health care , universal child care , paid sick leave , and higher levels of funding for public health. The Kaiser Family Foundation estimated that preventable hospitalizations of unvaccinated Americans in the second half of 2021 cost US$13.8 billion. There were also protest in regards to vaccine mandates in the United States. In January 2022, the US Supreme Court struck down an OSHA rule that mandated vaccination or a testing regimen for all companies with greater than 100 employees. The number of journalists imprisoned or detained increased worldwide; some detentions were related to the pandemic. The planned NATO " Defender 2020 " military exercise in Germany, Poland and the Baltic states , the largest NATO war exercise since the end of the Cold War , was held on a reduced scale. The Iranian government was heavily affected by the virus, which infected some two dozen parliament members and political figures. Iran President Hassan Rouhani wrote a public letter to world leaders asking for help on 14 March 2020, due to a lack of access to international markets. Saudi Arabia, which had launched a military intervention in Yemen in March 2015, declared a ceasefire. Diplomatic relations between Japan and South Korea worsened. South Korea criticised Japan's "ambiguous and passive quarantine efforts" after Japan announced travellers from South Korea must quarantine for two weeks. South Korean society was initially polarised on President Moon Jae-in 's response to the crisis; many Koreans signed petitions calling for Moon's impeachment or praising his response. Some countries passed emergency legislation. Some commentators expressed concern that it could allow governments to strengthen their grip on power. In Hungary, the parliament voted to allow Prime Minister Viktor Orbán to rule by decree indefinitely, suspend parliament and elections, and punish those deemed to have spread false information. In countries such as Egypt , Turkey , and Thailand , opposition activists and government critics were arrested for allegedly spreading fake news . In India, journalists criticising the government's response were arrested or issued warnings by police and authorities. The pandemic disrupted food systems worldwide, hitting at a time when hunger and undernourishment were rising- an estimated 690 million people lacked food security in 2019. Food access fell – driven by falling incomes, lost remittances, and disruptions to food production. In some cases, food prices rose. The pandemic and its accompanying lockdowns and travel restrictions slowed movement of food aid. According to the WHO, 811 million people were undernourished in 2020, "likely related to the fallout of COVID-19". The pandemic impacted educational systems in many countries. Many governments temporarily closed educational institutions, often replaced by online education . Other countries, such as Sweden, kept their schools open. As of September 2020, approximately 1.077 billion learners were affected due to school closures. School closures impacted students, teachers, and families with far-reaching economic and societal consequences. They shed light on social and economic issues, including student debt , digital learning , food insecurity, and homelessness , as well as access to childcare , health care, housing, internet, and disability services . The impact was more severe for disadvantaged children. The Higher Education Policy Institute reported that around 63% of students claimed worsened mental health as a result of the pandemic. The pandemic impacted global health for many conditions. Hospital visits fell. Visits for heart attack symptoms declined by 38% in the US and 40% in Spain. The head of cardiology at the University of Arizona said, "My worry is some of these people are dying at home because they're too scared to go to the hospital." People with strokes and appendicitis were less likely to seek treatment. Medical supply shortages impacted many people. The pandemic impacted mental health , increasing anxiety , depression, and post-traumatic stress disorder , affecting healthcare workers, patients and quarantined individuals. In late 2022, during the first northern hemisphere autumn and winter seasons following the widespread relaxation of global public health measures, North America and Europe experienced a surge in respiratory viruses and coinfections in both adults and children. This formed the beginnings of the 2022–2023 pediatric care crisis and what some experts have termed a " tripledemic " of seasonal influenza, Respiratory Syncytial Virus (RSV) , and SARS-CoV-2 throughout North America. In the United Kingdom, pediatric infections also began to spike beyond pre-pandemic levels, albeit with different illnesses, such as Group A streptococcal infection and resultant scarlet fever . As of mid-December 2022, 19 children in the UK had died due to Strep A and the wave of infections had begun to spread into North America and Mainland Europe. The B/Yamagata lineage of influenza B might have become extinct in 2020/2021 due to COVID-19 pandemic measures. There have been no naturally occurring cases confirmed since March 2020. In 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine , reducing the number of lineages targeted by the vaccine from four to three. The pandemic and the reaction to it positively affected the environment and climate as a result of reduced human activity. During the " anthropause ", fossil fuel use decreased, resource consumption declined, and waste disposal improved, generating less pollution. Planned air travel and vehicle transportation declined. In China, lockdowns and other measures resulted in a 26% decrease in coal consumption, and a 50% reduction in nitrogen oxides emissions. In 2020, a worldwide study on mammalian wildlife responses to human presence during COVID lockdowns found complex patterns of animal behavior. Carnivores were generally less active when humans were around, while herbivores in developed areas were more active. Among other findings, this suggested that herbivores may view humans as a shield against predators, highlighting the importance of location and human presence history in understanding wildlife responses to changes in human activity in a given area. A wide variety of largely mammalian species, both captive and wild, have been shown to be susceptible to SARS-CoV-2, with some encountering a particularly high degree of fatal outcomes. In particular, both farmed and wild mink have developed highly symptomatic and severe COVID-19 infections, with a mortality rate as high as 35–55% according to one study. White-tailed deer , on the other hand, have largely avoided severe outcomes but have effectively become natural reservoirs of the virus, with large numbers of free-ranging deer infected throughout the US and Canada, including approximately 80% of Iowa 's wild deer herd. An August 2023 study appeared to confirm the status of white-tailed deer as a disease reservoir, noting that the viral evolution of SARS-CoV-2 in deer occurs at triple the rate of its evolution in humans and that infection rates remained high, even in areas rarely frequented by humans. Heightened prejudice, xenophobia , and racism toward people of Chinese and East Asian descent were documented around the world. Reports from February 2020, when most confirmed cases were confined to China, cited racist sentiments about Chinese people 'deserving' the virus. Individuals of Asian descent in Europe and North America reported increasing instances of racially-motivated abuse and assaults as a result of the pandemic. US President Donald Trump was criticised for referring to SARS-CoV-2 as the "Chinese Virus" and "Kung Flu", terms which were condemned as being racist and xenophobic. Age-based discrimination against older adults increased during the pandemic. This was attributed to their perceived vulnerability and subsequent physical and social isolation measures, which, coupled with their reduced social activity, increased dependency on others. Similarly, limited digital literacy left the elderly more vulnerable to isolation, depression, and loneliness. In a correspondence published in The Lancet in 2021, German epidemiologist Günter Kampf described the harmful effects of "inappropriate stigmatisation of unvaccinated people, who include our patients, colleagues, and other fellow citizens", noting the evidence that vaccinated individuals play a large role in transmission. American bioethicist Arthur Caplan responded to Kampf, writing "Criticising [the unvaccinated] who... wind up in hospitals and morgues in huge numbers, put stress on finite resources, and prolong the pandemic... is not stigmatising, it is deserved moral condemnation." In January 2022, Amnesty International urged Italy to change their anti-COVID-19 restrictions to avoid discrimination against unvaccinated people, saying that "the government must continue to ensure that the entire population can enjoy its fundamental rights." The restrictions included mandatory vaccination over the age of 50, and mandatory vaccination to use public transport. The pandemic triggered massive changes in behaviour, from increased Internet commerce to cultural changes in the workplace. Online retailers in the US posted $791.70 billion in sales in 2020, an increase of 32.4% from $598.02 billion the year before. Home delivery orders increased, while indoor restaurant dining shut down due to lockdown orders or low sales. Hackers, cybercriminals and scammers took advantage of the changes to launch new online attacks. Education in some countries temporarily shifted from physical attendance to video conferencing. Massive layoffs shrank the airline, travel, hospitality, and other industries. Despite most corporations implementing measures to address COVID-19 in the workplace, a poll from Catalyst found that as many as 68% of employees around the world felt that these policies were only performative and "not genuine". The pandemic led to a surge in remote work . According to a Gallup poll , only 4% of US employees were fully remote before the pandemic, compared to 43% in May 2020. Among white collar workers, that shift was more pronounced, with 6% increasing to 65% in the same period. That trend continued in later stages of the pandemic, with many workers choosing to remain remote even after workplaces reopened. Many Nordic, European, and Asian companies increased their recruitment of international remote workers even as the pandemic waned, partially to save on labor costs. This also led to a talent drain in the global south and in remote areas in the global north. High cost of living and dense urban areas also lost office real estate value due to remote worker exodus. By May 2023, due to increasing layoffs and concerns over productivity, some white collar workplaces in the US had resorted to performance review penalties and indirect incentives (e.g. donations to charity) to encourage workers to return to the office. A 2021 study noted that the COVID-19 pandemic had increased interest in epidemics and infectious diseases among both historians and the general public. Prior to the pandemic, these topics were usually overlooked by "general" history and only received attention in the history of medicine . Many comparisons were made between the COVID-19 and 1918 influenza pandemics , including the development of anti-mask movements, the widespread promotion of misinformation and the impact of socioeconomic disparities . In some areas, religious groups exacerbated the spread of the virus, through large gatherings and the dissemination of misinformation. Some religious leaders decried what they saw as violations of religious freedom. In other cases, religious identity was a beneficial factor for health, increasing compliance with public health measures and protecting against the negative effects of isolation on mental wellbeing. Some news organizations removed their online paywalls for some or all of their pandemic-related articles and posts. Many scientific publishers provided pandemic-related journal articles to the public free of charge as part of the National Institutes of Health's COVID-19 Public Health Emergency Initiative. According to one estimate from researchers at the University of Rome, 89.5% of COVID-19-related papers were open access, compared to an average of 48.8% for the ten most deadly human diseases. The share of papers published on preprint servers prior to peer review increased dramatically. Misinformation and conspiracy theories about the pandemic have been widespread; they travel through mass media , social media and text messaging. In March 2020, WHO declared an " infodemic " of incorrect information. Cognitive biases , such as confirmation bias , are linked to conspiracy beliefs, including COVID-19 vaccine hesitancy . Misinformation and conspiracy theories about the pandemic have been widespread; they travel through mass media , social media and text messaging. In March 2020, WHO declared an " infodemic " of incorrect information. Cognitive biases , such as confirmation bias , are linked to conspiracy beliefs, including COVID-19 vaccine hesitancy . The COVID-19 pandemic had a major impact on popular culture. It was included in the narratives of ongoing pre-pandemic television series and become a central narrative in new ones, with mixed results. Writing for The New York Times about the then-upcoming BBC sitcom Pandemonium on 16 December 2020, David Segal asked, "Are we ready to laugh about Covid-19? Or rather, is there anything amusing, or recognizable in a humorous way, about life during a plague, with all of its indignities and setbacks, not to mention its rituals and rules." The pandemic had driven some people to seek peaceful escapism in media, while others were drawn towards fictional pandemics (e.g. zombie apocalypses ) as an alternate form of escapism. Common themes have included contagion , isolation and loss of control . Many drew comparisons to the fictional film Contagion (2011), praising its accuracies while noting some differences, such as the lack of an orderly vaccine rollout. As people turned to music to relieve emotions evoked by the pandemic, Spotify listenership showed that classical, ambient and children's genres grew, while pop, country and dance remained relatively stable. On 5 May 2023, the WHO declared that the pandemic was no longer a public health emergency of international concern . This led several media outlets to incorrectly report that this meant the pandemic was "over". The WHO commented to Full Fact that it was unlikely to declare the pandemic over "in the near future" and mentioned cholera , which it considers to have continued to be a pandemic since 1961 . The WHO does not have an official category for pandemics or make declarations of when pandemics start or end. In June 2023, Hans Kluge , director of the WHO in Europe, commented that "While the international public health emergency may have ended, the pandemic certainly has not". The WHO in Europe launched a transition plan to manage the public health response to COVID-19 in the coming years and prepare for possible future emergencies. In June 2022, an article in Human Genomics said that the pandemic was still "raging", but that "now is the time to explore the transition from the pandemic to the endemic phase." A March 2022 review declared the transition to endemic status to be "inevitable". A June 2022 review predicted that the virus that causes COVID-19 would become the fifth endemic seasonal coronavirus, alongside four other human coronaviruses . A February 2023 review of the four common cold coronaviruses concluded that the virus would become seasonal and, like the common cold, cause less severe disease for most people. As of 2023 [ update ] the transition to endemic COVID-19 may take years or decades. In June 2022, an article in Human Genomics said that the pandemic was still "raging", but that "now is the time to explore the transition from the pandemic to the endemic phase." A March 2022 review declared the transition to endemic status to be "inevitable". A June 2022 review predicted that the virus that causes COVID-19 would become the fifth endemic seasonal coronavirus, alongside four other human coronaviruses . A February 2023 review of the four common cold coronaviruses concluded that the virus would become seasonal and, like the common cold, cause less severe disease for most people. As of 2023 [ update ] the transition to endemic COVID-19 may take years or decades. Despite strong economic rebounds following the initial lockdowns in early 2020, towards the latter phases of the pandemic, many countries began to experience long-term economic effects. Several countries saw high inflation rates which had global impacts, particularly in developing countries. Some economic impacts such as supply chain and trade operations were seen as more permanent as the pandemic exposed major weaknesses in these systems. In Australia, the pandemic caused an increase in occupational burnout in 2022. During the pandemic, a large percentage of workers in Canada came to prefer working from home, which had an impact on the traditional work model. Some corporations made efforts to force workers to return to work on-site, while some embraced the idea. There was a "travel boom" causing air travel to recover at rates faster than anticipated, and the aviation industry became profitable in 2023 for the first time since 2019, before the pandemic. However, economic issues meant some predicted that the boom would begin to slow down. Business travel on airlines was still below pre-pandemic levels and is predicted not to recover. An increase in excess deaths from underlying causes not related to COVID-19 has been largely blamed on systematic issues causing delays in health care and screening during the pandemic, which has resulted in an increase of non-COVID-19 related deaths. During the pandemic, millions of children missed out on vaccinations as countries focused efforts on combating COVID-19. Efforts were made to increase vaccination rates among children in low-income countries . These efforts were successful in increasing vaccination rates for some diseases, though the UN noted that post-pandemic measles vaccinations were still falling behind. Some of the decrease in immunization was driven by an increase in mistrust of public health officials. This was seen in both low-income and high-income countries. Several African countries saw a decline in vaccinations due to misinformation around the pandemic flowing into other areas. Immunization rates have yet to recover in the United States and the United Kingdom. Despite strong economic rebounds following the initial lockdowns in early 2020, towards the latter phases of the pandemic, many countries began to experience long-term economic effects. Several countries saw high inflation rates which had global impacts, particularly in developing countries. Some economic impacts such as supply chain and trade operations were seen as more permanent as the pandemic exposed major weaknesses in these systems. In Australia, the pandemic caused an increase in occupational burnout in 2022. During the pandemic, a large percentage of workers in Canada came to prefer working from home, which had an impact on the traditional work model. Some corporations made efforts to force workers to return to work on-site, while some embraced the idea. There was a "travel boom" causing air travel to recover at rates faster than anticipated, and the aviation industry became profitable in 2023 for the first time since 2019, before the pandemic. However, economic issues meant some predicted that the boom would begin to slow down. Business travel on airlines was still below pre-pandemic levels and is predicted not to recover. An increase in excess deaths from underlying causes not related to COVID-19 has been largely blamed on systematic issues causing delays in health care and screening during the pandemic, which has resulted in an increase of non-COVID-19 related deaths. During the pandemic, millions of children missed out on vaccinations as countries focused efforts on combating COVID-19. Efforts were made to increase vaccination rates among children in low-income countries . These efforts were successful in increasing vaccination rates for some diseases, though the UN noted that post-pandemic measles vaccinations were still falling behind. Some of the decrease in immunization was driven by an increase in mistrust of public health officials. This was seen in both low-income and high-income countries. Several African countries saw a decline in vaccinations due to misinformation around the pandemic flowing into other areas. Immunization rates have yet to recover in the United States and the United Kingdom.

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Pandemic influenza

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United States influenza statistics by flu season

US influenza statistics by flu season . From the Centers for Disease Control and Prevention page called "Disease Burden of Flu": "Each year CDC estimates the burden of influenza in the U.S. CDC uses modeling to estimate the number of flu illnesses, medical visits, hospitalizations, and deaths related to flu that occurred in a given season. The methods used to calculate these estimates are described on CDC's webpage, How CDC Estimates the Burden of Seasonal Flu in the U.S. " The tables below include the latest available years the CDC has provided on their website. UI = uncertainty interval . Row numbers are static. Other columns are sortable. This allows ranking of any column. * 2019 to 2020 season is a preliminary estimate.UI = uncertainty interval . Row numbers are static. Other columns are sortable. This allows ranking of any column. * 2019 to 2020 season is a preliminary estimate.

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Pandemic influenza

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Canine influenza

Canine influenza ( dog flu ) is influenza occurring in canine animals. Canine influenza is caused by varieties of influenzavirus A , such as equine influenza virus H3N8 , which was discovered to cause disease in canines in 2004. Because of the lack of previous exposure to this virus, dogs have no natural immunity to it. Therefore, the disease is rapidly transmitted between individual dogs. Canine influenza may be endemic in some regional dog populations of the United States. It is a disease with a high morbidity (incidence of symptoms) but a low incidence of death . A newer form was identified in Asia during the 2000s and has since caused outbreaks in the US as well. It is a mutation of H3N2 that adapted from its avian influenza origins. Vaccines have been developed for both strains. The two strains of Type A influenza virus found in canines are A(H3N2) and A(H3N8). Over time, there has been a discovery of sources of transmissions, identification of specific symptoms and the creation of vaccines. The highly contagious equine influenza A virus subtype H3N8 was found to have been the cause of Greyhound race dog fatalities from a respiratory illness at a Florida racetrack in January 2004. The exposure and transfer apparently occurred at horse-racing tracks, where dog racing had also occurred. This was the first evidence of an influenza A virus causing disease in dogs. However, serum collected from racing Greyhounds between 1984 and 2004 and tested for canine influenza virus (CIV) in 2007 had positive tests going as far back as 1999. CIV possibly caused some of the respiratory disease outbreaks at tracks between 1999 and 2003. H3N8 was also responsible for a major dog-flu outbreak in New York state in all breeds of dogs. From January to May 2005, outbreaks occurred at 20 racetracks in 10 states ( Arizona , Arkansas , Colorado , Florida, Iowa , Kansas , Massachusetts , Rhode Island , Texas , and West Virginia ). As of August 2006, dog flu has been confirmed in 22 U.S. states, including pet dogs in Wyoming, California, Connecticut, Delaware, and Hawaii. Three areas in the United States may now be considered endemic for CIV due to continuous waves of cases: New York, southern Florida, and northern Colorado/southern Wyoming. No evidence shows the virus can be transferred to people, cats, or other species. H5N1 ( avian influenza ) was also shown to cause death in one dog in Thailand , following ingestion of an infected duck . The H3N2 virus made its first appearance in Canada at the start of 2018, following the importation of two unknowingly infected canines from South Korea. In 2006-2007 canine H3N2 first had reports in South Korea and was thought to be transferred to dogs from avian origins ( avian influenza H3N2). It was not until 2015 that the canine H3N2 strain was discovered in the United States after there was an outbreak of dogs having respiratory infections in Chicago. As canine H3N2 influenza began to spread through the United States, in 2016 cats in an Indiana began to show symptoms of the disease as well, it is believed they were infected by coming in to contact with sick dogs. Following this incidence, reports of the virus possibly spreading, with two other canines reporting alarming symptoms, were made public. By March 5th, 25 cases of infection were reportedly spread, although the number is thought to be closer to approximately 100. Influenza A viruses are enveloped , negative sense , single-stranded RNA viruses . Genome analysis has shown that H3N8 was transferred from horses to dogs and then adapted to dogs through point mutations in the genes . The incubation period is two to five days, and viral shedding may occur for seven to ten days following the onset of symptoms. It does not induce a persistent carrier state. [ citation needed ] In late 2022, together with Bordetella bronchiseptica and other respiratory pathogens, the H3N2 canine flu virus experienced a surge in canine infections. This was partially due to increased human travel and reopened offices following the relaxation of COVID-19 pandemic public health measures, leading to large numbers of dogs being placed together in kennels and doggy day care centers. Changing pet ownership behaviors also led to overcrowded animal shelters, which had been emptied at the height of the pandemic. The infection of canine influenza can be transmitted from animal to animal and almost all dogs that come in contact with the virus will contract it. This makes canine influenza most common among dogs but can also be transmitted to cats in a shelter or a household. Canine influenza is an airborne disease , when a dog coughs or sneezes they secrete respiratory droplets that are then inhaled by other animals causing infection. Kennels, dog parks, grooming parlors, and things alike are high risk areas for infections. About 80% of infected dogs with H3N8 show symptoms, usually mild (the other 20% have subclinical infections ), and the fatality rate for Greyhounds in early outbreaks was 5 to 8%, although the overall fatality rate in the general pet and shelter population is probably less than 1%. Most animals infected with canine influenza will show symptoms such as coughing, runny nose, fever, lethargy, eye discharge, and a reduced appetite lasting anywhere from 2-3 weeks. Symptoms of the mild form include a cough that lasts for 10 to 30 days and possibly a greenish nasal discharge. Dogs with the more severe form may have a high fever and pneumonia . Pneumonia in these dogs is not caused by the influenza virus, but by secondary bacterial infections. The fatality rate of dogs that develop pneumonia secondary to canine influenza can reach 50% if not given proper treatment. Necropsies in dogs that die from the disease have revealed severe hemorrhagic pneumonia and evidence of vasculitis . The presence of an upper respiratory tract infection in a dog that has been vaccinated for the other major causes of kennel cough increases suspicion of infection with canine influenza, especially in areas where the disease has been documented. A serum sample from a dog suspected of having canine influenza can be submitted to a laboratory that performs PCR tests for this virus. In June 2009, the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) approved the first canine influenza vaccine. This veterinarian provided vaccine help fight the infection and are preventative measures for dogs who are constantly facing exposure of the H3N8 and H3N2 strain. This vaccine must be given twice initially with a two-week break, then annually thereafter. A second form of canine influenza was first identified during 2006 in South Korea and southern China. The virus is an H3N2 variant that adapted from its avian influenza origins. An outbreak in the US was first reported in the Chicago area during 2015. Outbreaks were reported in several US states during the spring and summer of 2015 and had been reported in 25 states by late 2015. As of April 2015, the question of whether vaccination against the earlier strain offered protection had not been resolved. The US Department of Agriculture granted conditional approval for a canine H3N2-protective vaccine in December 2015. In March 2016, researchers reported that this strain had infected cats and suggested that it may be transmitted between them. The H3N2 virus as a stand-alone virus is deemed harmless to humans. According to the Windsor-Essex County Health Unit, it is only when the H3N2 virus strain combines with a human strain of flu, "those strains could combine to create a new virus." The possibility of this is unlikely; however, if an infected dog contracts a human flu, there stands a slight chance.

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