Datasets:

Jingmei

/

Pandemic_Wiki

like 0

Chikungunya

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

Scarlet fever

Scarlet fever , also known as scarlatina , is an infectious disease caused by Streptococcus pyogenes , a Group A streptococcus (GAS). It most commonly affects children between five and 15 years of age. The signs and symptoms include a sore throat , fever, headache, swollen lymph nodes , and a characteristic rash. The face is flushed and the rash is red and blanching . It typically feels like sandpaper and the tongue may be red and bumpy. The rash occurs as a result of capillary damage by exotoxins produced by S.pyogenes . On darker-pigmented skin the rash may be hard to discern. Scarlet fever develops in a small number of people who have strep throat or streptococcal skin infections . The bacteria are usually spread by people coughing or sneezing. It can also be spread when a person touches an object that has the bacteria on it and then touches their mouth or nose. The diagnosis is typically confirmed by culturing swabs of the throat . There is no vaccine for scarlet fever. Prevention is by frequent handwashing , not sharing personal items, and staying away from other people when sick. The disease is treatable with antibiotics , which reduce symptoms and spread, and prevent most complications. Outcomes with scarlet fever are typically good if treated. Long-term complications as a result of scarlet fever include kidney disease , rheumatic fever , and arthritis. In the early 20th century it was a leading cause of death in children, but even before the Second World War and the introduction of antibiotics, its severity was already declining, perhaps due to better living conditions, the introduction of better control measures, or a decline in the virulence of the bacteria. In recent years, there have been signs of antibiotic resistance ; there was an outbreak in Hong Kong in 2011 and in the UK in 2014, and occurrence of the disease rose by 68% in the UK between 2014 and 2018. Research published in October 2020 showed that infection of the bacterium by three viruses has led to more virulent strains of the bacterium. Scarlet fever typically presents with a sudden onset of sore throat , fever, and malaise . Headache, nausea, vomiting and abdominal pain may also be present. Scarlet fever usually follows from a group A streptococcal infection that involves a strep throat such as streptococcal tonsillitis or more usually streptococcal pharyngitis . Often these can present together known as pharyngotonsillitis . The signs and symptoms are therefore those of a strep throat but these are followed by the inclusion of the characteristic widespread rash . The rash usually appears one to two days later but may appear before or up to seven days following feeling ill. It generally hurts to swallow. However, not all cases present with a fever, the degree of tiredness may vary, the sore throat and tongue changes might be slight or absent, and the rash can be patchy rather than diffuse in some. [ page needed ] Cough, hoarseness, runny nose, diarrhea, and conjunctivitis are typically absent in scarlet fever; such symptoms indicate what is more likely a viral infection. Strep throat is usually associated with fatigue and a fever of over 39 °C (102.2 °F). The tonsils may appear red and enlarged and are typically covered in exudate . The throat may be red with small red spots on the roof of the mouth . The uvula can look red and swollen. 30% to 60% of cases have associated enlarged and tender lymph nodes in the neck. During the first two days of illness the tongue may have a whitish coating from which red swollen papillae protrude, giving the appearance of a "white strawberry tongue". After four to five days when the white coating sheds it becomes a "red strawberry tongue". The symptomatic appearance of the tongue is part of the rash that is characteristic of scarlet fever. The characteristic rash has been denoted as "scarlatiniform", and it appears as a diffuse redness of the skin with small bumps resembling goose bumps. It typically appears as small flat spots on the neck or torso before developing into small bumps that spread to the arms and legs. It tends to feel rough like sandpaper. The cheeks might look flushed with a pale area around the mouth. The scarlet fever rash generally looks red on white and pale skin, and might be difficult to visualise on brown or black skin, in whom the bumps are typically larger, the skin less like sandpaper, and the perioral pallor less obvious. The palms and soles are spared. The reddened skin blanches when pressure is applied to it. The skin may feel itchy, but is not painful. A more intense redness on the inside of skin folds and creases might be noticed. These are lines of petechiae , appearing as pink/red areas located in arm pits and elbow pits. It takes around a week for the main rash to disappear. This may be followed by several weeks of peeling of the skin of typically fingers and toes. The desquamation process usually begins on the face and progresses downward on the body. Sometimes, this peeling is the only sign that scarlet fever occurred. If the case of scarlet fever is uncomplicated, recovery from the fever and clinical symptoms, other than the process of desquamation, occurs in 5–10 days. After the desquamation, the skin will be left with a sunburned appearance. Children younger than five years old may have atypical presentations. Children younger than 3 years old can present with nasal congestion and a lower grade fever. Infants may present with symptoms of increased irritability and decreased appetite. The complications, which can arise from scarlet fever when left untreated or inadequately treated, can be divided into two categories: suppurative and nonsuppurative. Suppurative complications: These are rare complications that arise either from direct spread to structures that are close to the primary site of infection, or spread through the lymphatic system or blood. In the first case, scarlet fever may spread to the pharynx. Possible problems from this method of spread include peritonsillar or retropharyngeal abscesses, cellulitis , mastoiditis , or sinusitis . [ citation needed ] In the second case, the streptococcal infection may spread through the lymphatic system or the blood to areas of the body further away from the pharynx. A few examples of the many complications that can arise from those methods of spread include endocarditis , pneumonia , or meningitis . Nonsuppurative complications: These complications arise from certain subtypes of group A streptococci that cause an autoimmune response in the body through what has been termed molecular mimicry . In these cases, the antibodies which the person's immune system developed to attack the group A streptococci are also able to attack the person's own tissues. The following complications result, depending on which tissues in the person's body are targeted by those antibodies. Strep throat is usually associated with fatigue and a fever of over 39 °C (102.2 °F). The tonsils may appear red and enlarged and are typically covered in exudate . The throat may be red with small red spots on the roof of the mouth . The uvula can look red and swollen. 30% to 60% of cases have associated enlarged and tender lymph nodes in the neck. During the first two days of illness the tongue may have a whitish coating from which red swollen papillae protrude, giving the appearance of a "white strawberry tongue". After four to five days when the white coating sheds it becomes a "red strawberry tongue". The symptomatic appearance of the tongue is part of the rash that is characteristic of scarlet fever. The characteristic rash has been denoted as "scarlatiniform", and it appears as a diffuse redness of the skin with small bumps resembling goose bumps. It typically appears as small flat spots on the neck or torso before developing into small bumps that spread to the arms and legs. It tends to feel rough like sandpaper. The cheeks might look flushed with a pale area around the mouth. The scarlet fever rash generally looks red on white and pale skin, and might be difficult to visualise on brown or black skin, in whom the bumps are typically larger, the skin less like sandpaper, and the perioral pallor less obvious. The palms and soles are spared. The reddened skin blanches when pressure is applied to it. The skin may feel itchy, but is not painful. A more intense redness on the inside of skin folds and creases might be noticed. These are lines of petechiae , appearing as pink/red areas located in arm pits and elbow pits. It takes around a week for the main rash to disappear. This may be followed by several weeks of peeling of the skin of typically fingers and toes. The desquamation process usually begins on the face and progresses downward on the body. Sometimes, this peeling is the only sign that scarlet fever occurred. If the case of scarlet fever is uncomplicated, recovery from the fever and clinical symptoms, other than the process of desquamation, occurs in 5–10 days. After the desquamation, the skin will be left with a sunburned appearance. Children younger than five years old may have atypical presentations. Children younger than 3 years old can present with nasal congestion and a lower grade fever. Infants may present with symptoms of increased irritability and decreased appetite. The complications, which can arise from scarlet fever when left untreated or inadequately treated, can be divided into two categories: suppurative and nonsuppurative. Suppurative complications: These are rare complications that arise either from direct spread to structures that are close to the primary site of infection, or spread through the lymphatic system or blood. In the first case, scarlet fever may spread to the pharynx. Possible problems from this method of spread include peritonsillar or retropharyngeal abscesses, cellulitis , mastoiditis , or sinusitis . [ citation needed ] In the second case, the streptococcal infection may spread through the lymphatic system or the blood to areas of the body further away from the pharynx. A few examples of the many complications that can arise from those methods of spread include endocarditis , pneumonia , or meningitis . Nonsuppurative complications: These complications arise from certain subtypes of group A streptococci that cause an autoimmune response in the body through what has been termed molecular mimicry . In these cases, the antibodies which the person's immune system developed to attack the group A streptococci are also able to attack the person's own tissues. The following complications result, depending on which tissues in the person's body are targeted by those antibodies. Strep throat spreads by close contact among people, via respiratory droplets (for example, saliva or nasal discharge). A person in close contact with another person infected with group A streptococcal pharyngitis has a 35% chance of becoming infected. One in ten children who are infected with group A streptococcal pharyngitis will develop scarlet fever. The rash of scarlet fever, which is what differentiates this disease from an isolated group A strep pharyngitis (or strep throat), is caused by specific strains of group A streptococcus that produce a streptococcal pyrogenic exotoxin , which is mainly responsible for the skin manifestation of the infection. These toxin-producing strains cause scarlet fever in people who do not already have antitoxin antibodies . Streptococcal pyrogenic exotoxins – SPEs A, B, C. and F have been identified. The pyrogenic exotoxins, also called erythrogenic toxins , cause the erythematous rash of scarlet fever. The strains of group A streptococcus that cause scarlet fever need specific bacteriophages for there to be pyrogenic exotoxin production. Specifically, bacteriophage T12 is responsible for the production of speA. Streptococcal Pyrogenic Exotoxin A, speA, is the one most commonly associated with cases of scarlet fever that are complicated by the immune-mediated sequelae of acute rheumatic fever and post-streptococcal glomerulonephritis. These toxins are also known as " superantigens " because they can cause an extensive immune response by activating some of the cells that are mainly responsible for the person's immune system. Although the body responds to the toxins it encounters by making antibodies, those antibodies will only protect against that particular subset of toxins. They will not necessarily completely protect a person from future group A streptococcal infections, because there are 12 different pyrogenic exotoxins that may be produced by the disease, and future infections may produce a different subset of those toxins. The disease is caused by secretion of pyrogenic exotoxins by the infecting Streptococcus bacteria. Streptococcal pyrogenic exotoxin A ( speA ) is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates into the streptococcal genome from where the toxin is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome. The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses . It has a double-stranded DNA genome and on morphological grounds appears to be a member of the Siphoviridae . The speA gene was cloned and sequenced in 1986. It is 753 base pairs in length and encodes a 29.244 kilodalton (kDa) protein . The protein contains a putative 30-amino-acid signal peptide ; removal of the signal sequence gives a predicted molecular weight of 25.787 kDa for the secreted protein. Both a promoter and a ribosome binding site ( Shine-Dalgarno sequence ) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon . The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1. [ citation needed ] Streptococcal phages other than T12 may also carry the speA gene. The disease is caused by secretion of pyrogenic exotoxins by the infecting Streptococcus bacteria. Streptococcal pyrogenic exotoxin A ( speA ) is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates into the streptococcal genome from where the toxin is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome. The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses . It has a double-stranded DNA genome and on morphological grounds appears to be a member of the Siphoviridae . The speA gene was cloned and sequenced in 1986. It is 753 base pairs in length and encodes a 29.244 kilodalton (kDa) protein . The protein contains a putative 30-amino-acid signal peptide ; removal of the signal sequence gives a predicted molecular weight of 25.787 kDa for the secreted protein. Both a promoter and a ribosome binding site ( Shine-Dalgarno sequence ) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon . The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1. [ citation needed ] Streptococcal phages other than T12 may also carry the speA gene. Although the presentation of scarlet fever can be clinically diagnosed, further testing may be required to distinguish it from other illnesses. Also, history of a recent exposure to someone with strep throat can be useful in diagnosis. There are two methods used to confirm suspicion of scarlet fever; rapid antigen detection test and throat culture . The rapid antigen detection test is a very specific test but not very sensitive. This means that if the result is positive (indicating that the group A strep antigen was detected and therefore confirming that the person has a group A strep pharyngitis), then it is appropriate to treat the people with scarlet fever with antibiotics. But, if the rapid antigen detection test is negative (indicating that they do not have group A strep pharyngitis), then a throat culture is required to confirm, as the first test could have yielded a false negative result. In the early 21st century, the throat culture is the current "gold standard" for diagnosis. Serologic testing seeks evidence of the antibodies that the body produces against the streptococcal infection, including antistreptolysin-O and antideoxyribonuclease B. It takes the body 2–3 weeks to make these antibodies, so this type of testing is not useful for diagnosing a current infection. But it is useful when assessing a person who may have one of the complications from a previous streptococcal infection. Throat cultures done after antibiotic therapy can show if the infection has been removed. These throat swabs, however, are not indicated, because up to 25% of properly treated individuals can continue to carry the streptococcal infection while being asymptomatic. Scarlet fever might appear similar to Kawasaki disease , which has a characteristic red but not white strawberry tongue, and staphylococcal scarlatina which does not have the strawberry tongue at all. Other conditions that might appear similar include impetigo , erysipelas , measles , chickenpox , and hand-foot-and-mouth disease , and may be distinguished by the pattern of symptoms. Scarlet fever might appear similar to Kawasaki disease , which has a characteristic red but not white strawberry tongue, and staphylococcal scarlatina which does not have the strawberry tongue at all. Other conditions that might appear similar include impetigo , erysipelas , measles , chickenpox , and hand-foot-and-mouth disease , and may be distinguished by the pattern of symptoms. One method is long-term use of antibiotics to prevent future group A streptococcal infections. This method is only indicated for people who have had complications like recurrent attacks of acute rheumatic fever or rheumatic heart disease. Antibiotics are limited in their ability to prevent these infections since there are a variety of subtypes of group A streptococci that can cause the infection. Although there are currently no vaccines available, the vaccine approach has a greater likelihood of effectively preventing group A streptococcal infections in the future because vaccine formulations can target multiple subtypes of the bacteria. A vaccine developed by George and Gladys Dick in 1924 was discontinued [ when? ] due to poor efficacy and the introduction of antibiotics. Difficulties in vaccine development include the considerable strain variety of group A streptococci present in the environment and the amount of time and number of people needed for appropriate trials for safety and efficacy of any potential vaccine. There have been several attempts to create a vaccine in the past few decades. These vaccines, which are still in the development phase, expose the person to proteins present on the surface of the group A streptococci to activate an immune response that will prepare the person to fight and prevent future infections. There used to be a diphtheria scarlet fever vaccine. It was, however, found not to be effective. This product was discontinued by the end of World War II. [ citation needed ]Antibiotics to combat the streptococcal infection are the mainstay of treatment for scarlet fever. Prompt administration of appropriate antibiotics decreases the length of illness. Peeling of the outer layer of skin, however, will happen despite treatment. One of the main goals of treatment is to prevent the child from developing one of the suppurative or nonsuppurative complications, especially acute rheumatic fever. As long as antibiotics are started within nine days, it is very unlikely for the child to develop acute rheumatic fever. Antibiotic therapy has not been shown to prevent the development of post-streptococcal glomerulonephritis. Another important reason for prompt treatment with antibiotics is the ability to prevent transmission of the infection between children. An infected individual is most likely to pass on the infection to another person during the first two weeks. A child is no longer contagious (able to pass the infection to another child) after 24 hours of antibiotics. The antibiotic of choice is Penicillin V which is taken by mouth. In countries without a liquid Penicillin V product, children unable to take tablets can be given amoxicillin which comes in a liquid form and is equally effective. Duration of treatment is 10 days. Benzathine penicillin G can be given as a one time intramuscular injection as another alternative if swallowing pills is not possible. If the person is allergic to the family of antibiotics which both penicillin and amoxicillin are a part of ( beta-lactam antibiotics ), a first generation cephalosporin is used. Cephalosporin antibiotics, however, can still cause adverse reactions in people whose allergic reaction to penicillin is a Type 1 Hypersensitivity reaction . In those cases it is appropriate to choose clindamycin or erythromycin instead. Tonsillectomy , although once a reasonable treatment for recurrent streptococcal pharyngitis, is not indicated, as a person can still be infected with group A streptococcus without their tonsils. A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin , but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade. About 60% of circulating strains of the group A streptococcus that cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, according to Professor Yuen Kwok-yung , head of Hong Kong University 's microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years. [ citation needed ] There was also an outbreak in the UK in 2014, and the National Health Service reported a 68% increase in the number of S. pyogenes identified in laboratory reports between 2014 and 2018. New research published in October 2020 indicates that the bacterium appears to be getting more robust after being infected with viruses, specifically the North-East Asian serotype M12 (emm12) (group A Streptococcus, GAS). They found three new genes, acquired from viruses, which cause development of " superantigens " targeting white blood cells , resulting in a more virulent strain of the bacterium. A vaccine that will protect against the 180 to 200 types of bacteria causing the disease has been worked on for over 20 years, but as of 2020 [ update ] a safe one had not yet been developed. A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin , but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade. About 60% of circulating strains of the group A streptococcus that cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, according to Professor Yuen Kwok-yung , head of Hong Kong University 's microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years. [ citation needed ] There was also an outbreak in the UK in 2014, and the National Health Service reported a 68% increase in the number of S. pyogenes identified in laboratory reports between 2014 and 2018. New research published in October 2020 indicates that the bacterium appears to be getting more robust after being infected with viruses, specifically the North-East Asian serotype M12 (emm12) (group A Streptococcus, GAS). They found three new genes, acquired from viruses, which cause development of " superantigens " targeting white blood cells , resulting in a more virulent strain of the bacterium. A vaccine that will protect against the 180 to 200 types of bacteria causing the disease has been worked on for over 20 years, but as of 2020 [ update ] a safe one had not yet been developed. Scarlet fever occurs equally in both males and females. Children are most commonly infected, typically between 5–15 years old. Although streptococcal infections can happen at any time of year, infection rates peak in the winter and spring months, typically in colder climates. The morbidity and mortality of scarlet fever has declined since the 18th and 19th centuries when there were epidemics of this disease. Around 1900 the mortality rate in multiple places reached 25%. The improvement in prognosis can be attributed to the use of penicillin in the treatment of this disease. The frequency of scarlet fever cases has also been declining over the past century. There have been several reported outbreaks of the disease in various countries in the past decade. The reason for these increases remains unclear in the medical community. Between 2013 and 2016 population rates of scarlet fever in England increased from 8.2 to 33.2 per 100,000 and hospital admissions for scarlet fever increased by 97%. Further increases in the reporting of scarlet fever cases have been noted in England during the 2021–2022 season (September to September) and so far also in the season 2022–2023. The World Health Organization has reported an increase in scarlet fever (and iGAS – invasive GAS cases) in England, and other European countries during this time. Increases have been reported in France and Ireland. In the US, cases of scarlet fever are not reported, but as of December 2022, the CDC was looking at a possible increase in the numbers of invasive GAS infections reported in children. In late December 2022, the CDC's Health Alert Network issued an advisory on the reported increases in invasive GAS infections. It is unclear when a description of this disease was first recorded. Hippocrates , writing around 400 BC, described the condition of a person with a reddened skin and fever. The first unambiguous description of the disease in the medical literature appeared in the 1553 book De Tumoribus praeter Naturam by the Sicilian anatomist and physician Giovanni Filippo Ingrassia , where he referred to it as rossalia . He also made a point to distinguish that this presentation had different characteristics from measles . It was redescribed by Johann Weyer during an epidemic in lower Germany between 1564 and 1565; he referred to it as scarlatina anginosa . The first unequivocal description of scarlet fever appeared in a book by Joannes Coyttarus of Poitiers , De febre purpura epidemiale et contagiosa libri duo , which was published in 1578 in Paris. Daniel Sennert of Wittenberg described the classical 'scarlatinal desquamation' in 1572 and was also the first to describe the early arthritis , scarlatinal dropsy , and ascites associated with the disease. [ citation needed ] In 1675 the term that has been commonly used to refer to scarlet fever, "scarlatina", was written by Thomas Sydenham , an English physician. In 1827, Richard Bright was the first to recognize the involvement of the renal system in scarlet fever. [ citation needed ] The association between streptococci and disease was first described in 1874 by Theodor Billroth , discussing people with skin infections. Billroth also coined the genus name Streptococcus . In 1884 Friedrich Julius Rosenbach edited the name to its current one, Streptococcus pyogenes, after further looking at the bacteria in the skin lesions. The organism was first cultured in 1883 by the German surgeon Friedrich Fehleisen from erysipelas lesions. [ citation needed ] Also in 1884, the German physician Friedrich Loeffler was the first to show the presence of streptococci in the throats of people with scarlet fever. Because not all people with pharyngeal streptococci developed scarlet fever, these findings remained controversial for some time. The association between streptococci and scarlet fever was confirmed by Alphonse Dochez and George and Gladys Dick in the early 1900s. Also in 1884, the world's first convalescent home for people with scarlet fever was opened at Brockley Hill, Stanmore, founded by Mary Wardell . Nil Filatov (in 1895) and Clement Dukes (in 1894) described an exanthematous disease which they thought was a form of rubella , but in 1900, Dukes described it as a separate illness which came to be known as Dukes' disease , Filatov's disease, or fourth disease. However, in 1979, Keith Powell identified it as in fact the same illness as the form of scarlet fever which is caused by staphylococcal exotoxin and is known as staphylococcal scalded skin syndrome . Scarlet fever serum from horses' blood was used in the treatment of children beginning in 1900 and reduced mortality rates significantly. In 1906, Austrian pediatrician Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever. Bacteriophages were discovered in 1915 by Frederick Twort . His work was overlooked and bacteriophages were later rediscovered by Felix d'Herelle in 1917. The specific association of scarlet fever with the group A streptococci had to await the development of Rebecca Lancefield 's streptococcal grouping scheme in the 1920s. George and Gladys Dick showed that cell-free filtrates could induce the erythematous reaction characteristic of scarlet fever, proving that this reaction was due to a toxin. Karelitz and Stempien discovered that extracts from human serum globulin and placental globulin can be used as lightening agents for scarlet fever and this was used later as the basis for the Dick test. The association of scarlet fever and bacteriophages was described in 1926 by Cantacuzène ( Ioan Cantacuzino ) and Bonciu. There was a widespread epidemic of scarlet fever in 1922. Amongst the victims of this epidemic was Agathe Whitehead . An antitoxin for scarlet fever was developed in 1924. The discovery of penicillin and its subsequent widespread use significantly reduced the mortality of this once-feared disease. The first toxin which causes this disease was cloned and sequenced in 1986 by Weeks and Ferretti. The incidence of scarlet fever was reported to be increasing in countries including England, Wales, South Korea, Vietnam, China, and Hong Kong in the 2010s; the cause had not been established as of 2018. Cases were also reported to be increasing after the easing of restrictions due to the COVID pandemic that started in 2020. The Dick test, developed in 1924 by George F. Dick and Gladys Dick , was used to identify those susceptible to scarlet fever. The Dick test involved injecting a diluted strain of the streptococci known to cause scarlet fever; a reaction in the skin at the injection site identified people susceptible to developing scarlet fever. The reaction could be seen four hours after the injection, but was more noticeable after 24 hours. If no reaction was seen in the skin, then the person was assumed not to be at risk from the disease, having developed immunity to it. The Dick test, developed in 1924 by George F. Dick and Gladys Dick , was used to identify those susceptible to scarlet fever. The Dick test involved injecting a diluted strain of the streptococci known to cause scarlet fever; a reaction in the skin at the injection site identified people susceptible to developing scarlet fever. The reaction could be seen four hours after the injection, but was more noticeable after 24 hours. If no reaction was seen in the skin, then the person was assumed not to be at risk from the disease, having developed immunity to it.

Wiki

Chikungunya

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

Waterborne disease

Waterborne diseases are conditions (meaning adverse effects on human health, such as death, disability, illness or disorders) : 47 caused by pathogenic micro-organisms that are transmitted by water . These diseases can be spread while bathing, washing, drinking water, or by eating food exposed to contaminated water. They are a pressing issue in rural areas amongst developing countries all over the world. While diarrhea and vomiting are the most commonly reported symptoms of waterborne illness, other symptoms can include skin, ear, respiratory, or eye problems. Lack of clean water supply, sanitation and hygiene (WASH) are major causes for the spread of waterborne diseases in a community. Therefore, reliable access to clean drinking water and sanitation is the main method to prevent waterborne diseases. Microorganisms causing diseases that characteristically are waterborne prominently include protozoa and bacteria , many of which are intestinal parasites , or invade the tissues or circulatory system through walls of the digestive tract. Various other waterborne diseases are caused by viruses . Yet other important classes of waterborne diseases are caused by metazoan parasites. Typical examples include certain Nematoda , that is to say "roundworms". As an example of waterborne Nematode infections, one important waterborne nematode disease is Dracunculiasis . It is acquired by swallowing water in which certain copepoda occur that act as vectors for the Nematoda. Anyone swallowing a copepod that happens to be infected with Nematode larvae in the genus Dracunculus , becomes liable to infection. The larvae cause guinea worm disease . Another class of waterborne metazoan pathogens are certain members of the Schistosomatidae , a family of blood flukes . They usually infect people that make skin contact with the water. Blood flukes are pathogens that cause Schistosomiasis of various forms, more or less seriously affecting hundreds of millions of people worldwide. The term waterborne disease is reserved largely for infections that predominantly are transmitted through contact with or consumption of microbially polluted water . Many infections may be transmitted by microbes or parasites that accidentally, possibly as a result of exceptional circumstances, have entered the water. However, the fact that there might be an occasional infection need not mean that it is useful to categorize the resulting disease as "waterborne". Nor is it common practice to refer to diseases such as malaria as "waterborne" just because mosquitoes have aquatic phases in their life cycles, or because treating the water they inhabit happens to be an effective strategy in control of the mosquitoes that are the vectors . [ citation needed ] A related term is "water-related disease" which is defined as "any significant or widespread adverse effects on human health, such as death, disability, illness or disorders, caused directly or indirectly by the condition, or changes in the quantity or quality of any water". : 47 Water-related diseases are grouped according to their transmission mechanism: water borne, water hygiene, water based, water related. : 47 The main transmission mode for waterborne diseases is ingestion of contaminated water. [ citation needed ]Lack of clean water supply, sanitation and hygiene (WASH) are major causes for the spread of waterborne diseases in a community. The fecal–oral route is a disease transmission pathway for waterborne diseases. [ citation needed ] Poverty also increases the risk of communities to be affected by waterborne diseases. For example, the economic level of a community impacts their ability to have access to clean water. Less developed countries might be more at risk for potential outbreaks of waterborne diseases but more developed regions also are at risk to waterborne disease outbreaks. Global climate change has increased the occurrence of some infectious diseases . Infectious diseases whose transmission is impacted by climate change include, for example, vector-borne diseases like dengue fever , malaria , tick-borne diseases , leishmaniasis , zika fever , chikungunya and Ebola . One mechanism contributing to increased disease transmission is that climate change is altering the geographic range and seasonality of the insects (or disease vectors ) that can carry the diseases. Scientists stated a clear observation in 2022: "the occurrence of climate-related food-borne and waterborne diseases has increased (very high confidence)." : 11Global climate change has increased the occurrence of some infectious diseases . Infectious diseases whose transmission is impacted by climate change include, for example, vector-borne diseases like dengue fever , malaria , tick-borne diseases , leishmaniasis , zika fever , chikungunya and Ebola . One mechanism contributing to increased disease transmission is that climate change is altering the geographic range and seasonality of the insects (or disease vectors ) that can carry the diseases. Scientists stated a clear observation in 2022: "the occurrence of climate-related food-borne and waterborne diseases has increased (very high confidence)." : 11Reliable access to clean drinking water and sanitation is the main method to prevent waterborne diseases. The aim is to break the fecal–oral route of disease transmission. [ citation needed ]According to the World Health Organization , waterborne diseases account for an estimated 3.6% of the total DALY (disability- adjusted life year) global burden of disease , and cause about 1.5 million human deaths annually. The World Health Organization estimates that 58% of that burden, or 842,000 deaths per year, is attributable to a lack of safe drinking water supply, sanitation and hygiene (summarized as WASH ). The Waterborne Disease and Outbreak Surveillance System (WBDOSS) is the principal database used to identify the causative agents, deficiencies, water systems, and sources associated with waterborne disease and outbreaks in the United States. Since 1971, the Centers for Disease Control and Prevention (CDC) , the Council of State and Territorial Epidemiologists (CSTE), and the US Environmental Protection Agency (EPA) have maintained this surveillance system for collecting and reporting data on "waterborne disease and outbreaks associated with recreational water, drinking water, environmental, and undetermined exposures to water." "Data from WBDOSS have supported EPA efforts to develop drinking water regulations and have provided guidance for CDC's recreational water activities." WBDOSS relies on complete and accurate data from public health departments in individual states, territories, and other U.S. jurisdictions regarding waterborne disease and outbreak activity. In 2009, reporting to the WBDOSS transitioned from a paper form to the electronic National Outbreak Reporting System (NORS) . Annual or biennial surveillance reports of the data collected by the WBDOSS have been published in CDC reports from 1971 to 1984; since 1985, surveillance data have been published in the Morbidity and Mortality Weekly Report (MMWR) . WBDOSS and the public health community work together to look into the causes of contaminated water leading to waterborne disease outbreaks and maintaining those outbreaks. They do so by having the public health community investigating the outbreaks and WBDOSS receiving the reports. The Waterborne Disease and Outbreak Surveillance System (WBDOSS) is the principal database used to identify the causative agents, deficiencies, water systems, and sources associated with waterborne disease and outbreaks in the United States. Since 1971, the Centers for Disease Control and Prevention (CDC) , the Council of State and Territorial Epidemiologists (CSTE), and the US Environmental Protection Agency (EPA) have maintained this surveillance system for collecting and reporting data on "waterborne disease and outbreaks associated with recreational water, drinking water, environmental, and undetermined exposures to water." "Data from WBDOSS have supported EPA efforts to develop drinking water regulations and have provided guidance for CDC's recreational water activities." WBDOSS relies on complete and accurate data from public health departments in individual states, territories, and other U.S. jurisdictions regarding waterborne disease and outbreak activity. In 2009, reporting to the WBDOSS transitioned from a paper form to the electronic National Outbreak Reporting System (NORS) . Annual or biennial surveillance reports of the data collected by the WBDOSS have been published in CDC reports from 1971 to 1984; since 1985, surveillance data have been published in the Morbidity and Mortality Weekly Report (MMWR) . WBDOSS and the public health community work together to look into the causes of contaminated water leading to waterborne disease outbreaks and maintaining those outbreaks. They do so by having the public health community investigating the outbreaks and WBDOSS receiving the reports. Waterborne diseases can have a significant impact on the economy. People who are infected by a waterborne disease are usually confronted with related healthcare costs. This is especially the case in developing countries. On average, a family spends about 10% of the monthly households income per person infected. Waterborne diseases can have a significant impact on the economy. People who are infected by a waterborne disease are usually confronted with related healthcare costs. This is especially the case in developing countries. On average, a family spends about 10% of the monthly households income per person infected. Waterborne diseases were once wrongly explained by the miasma theory , the theory that bad air causes the spread of diseases. However, people started to find a correlation between water quality and waterborne diseases, which led to different water purification methods, such as sand filtering and chlorinating their drinking water. Founders of microscopy , Antonie van Leeuwenhoek and Robert Hooke , used the newly invented microscope to observe for the first time small material particles that were suspended in the water, laying the groundwork for the future understanding of waterborne pathogens and waterborne diseases.

Wiki

Chikungunya

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

Pathogen

In biology , a pathogen ( Greek : πάθος , pathos "suffering", "passion" and -γενής , -genēs "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent , or simply a germ . The term pathogen came into use in the 1880s. Typically, the term pathogen is used to describe an infectious microorganism or agent, such as a virus, bacterium, protozoan , prion , viroid , or fungus. Small animals, such as helminths and insects, can also cause or transmit disease. However, these animals are usually referred to as parasites rather than pathogens. The scientific study of microscopic organisms, including microscopic pathogenic organisms, is called microbiology , while parasitology refers to the scientific study of parasites and the organisms that host them. There are several pathways through which pathogens can invade a host. The principal pathways have different episodic time frames, but soil has the longest or most persistent potential for harboring a pathogen. Diseases in humans that are caused by infectious agents are known as pathogenic diseases. Not all diseases are caused by pathogens, such as black lung from exposure to the pollutant coal dust , genetic disorders like sickle cell disease , and autoimmune diseases like lupus .Pathogenicity is the potential disease-causing capacity of pathogens, involving a combination of infectivity (pathogen's ability to infect hosts) and virulence (severity of host disease). Koch's postulates are used to establish causal relationships between microbial pathogens and diseases. Whereas meningitis can be caused by a variety of bacterial, viral, fungal, and parasitic pathogens, cholera is only caused by some strains of Vibrio cholerae . Additionally, some pathogens may only cause disease in hosts with an immunodeficiency . These opportunistic infections often involve hospital-acquired infections among patients already combating another condition. Infectivity involves pathogen transmission through direct contact with the bodily fluids or airborne droplets of infected hosts, indirect contact involving contaminated areas/items, or transfer by living vectors like mosquitos and ticks . The basic reproduction number of an infection is the expected number of subsequent cases it is likely to cause through transmission. Virulence involves pathogens extracting host nutrients for their survival, evading host immune systems by producing microbial toxins and causing immunosuppression . Optimal virulence describes a theorized equilibrium between a pathogen spreading to additional hosts to parasitize resources, while lowering their virulence to keep hosts living for vertical transmission to their offspring. Algae are single-celled eukaryotes that are generally non-pathogenic. Green algae from the genus Prototheca lack chlorophyll and are known to cause the disease protothecosis in humans, dogs, cats, and cattle, typically involving the soil-associated species Prototheca wickerhami . Bacteria are single-celled prokaryotes that range in size from 0.15 and 700 μM. While the vast majority are either harmless or beneficial to their hosts, such as members of the human gut microbiome that support digestion, a small percentage are pathogenic and cause infectious diseases. Bacterial virulence factors include adherence factors to attach to host cells, invasion factors supporting entry into host cells, capsules to prevent opsonization and phagocytosis , toxins, and siderophores to acquire iron. The bacterial disease tuberculosis , primarily caused by Mycobacterium tuberculosis , has one of the highest disease burdens , killing 1.6 million people in 2021, mostly in Africa and Southeast Asia. Bacterial pneumonia is primarily caused by Streptococcus pneumoniae , Staphylococcus aureus , Klebsiella pneumoniae , and Haemophilus influenzae . Foodborne illnesses typically involve Campylobacter , Clostridium perfringens , Escherichia coli , Listeria monocytogenes , and Salmonella . Other infectious diseases caused by pathogenic bacteria include tetanus , typhoid fever , diphtheria , and leprosy . Fungi are eukaryotic organisms that can function as pathogens. There are approximately 300 known fungi that are pathogenic to humans, including Candida albicans , which is the most common cause of thrush , and Cryptococcus neoformans , which can cause a severe form of meningitis . Typical fungal spores are 4.7 μm long or smaller. Prions are misfolded proteins that transmit their abnormal folding pattern to other copies of the protein without using nucleic acids . Besides obtaining prions from others, these misfolded proteins arise from genetic differences, either due to family history or sporadic mutations. Plants uptake prions from contaminated soil and transport them into their stem and leaves, potentially transmitting the prions to herbivorous animals . Additionally, wood, rocks, plastic, glass, cement, stainless steel, and aluminum have been shown binding, retaining, and releasing prions, showcasing that the proteins resist environmental degradation. Prions are best known for causing transmissible spongiform encephalopathy (TSE) diseases like Creutzfeldt–Jakob disease (CJD), variant Creutzfeldt–Jakob disease (vCJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia (FFI), and kuru in humans. While prions are typically viewed as pathogens that cause protein amyloid fibers to accumulate into neurodegenerative plaques, Susan Lindquist led research showing that yeast use prions to pass on evolutionarily beneficial traits. Not to be confused with virusoids or viruses, viroids are the smallest known infectious pathogens. Viroids are small single-stranded, circular RNA that are only known to cause plant diseases, such as the potato spindle tuber viroid that affects various agricultural crops. Viroid RNA is not protected by a protein coat, and it does not encode any proteins, only acting as a ribozyme to catalyze other biochemical reactions. Viruses are generally between 20-200 nm in diameter. For survival and replication, viruses inject their genome into host cells, insert those genes into the host genome, and hijack the host's machinery to produce hundreds of new viruses until the cell bursts open to release them for additional infections. The lytic cycle describes this active state of rapidly killing hosts, while the lysogenic cycle describes potentially hundreds of years of dormancy while integrated in the host genome. Alongside the taxonomy organized by the International Committee on Taxonomy of Viruses (ICTV), the Baltimore classification separates viruses by seven classes of mRNA production: Protozoans are single-celled eukaryotes that feed on microorganisms and organic tissues. Many protozoans act as pathogenic parasites to cause diseases like malaria , amoebiasis , giardiasis , toxoplasmosis , cryptosporidiosis , trichomoniasis , Chagas disease , leishmaniasis , African trypanosomiasis (sleeping sickness), Acanthamoeba keratitis , and primary amoebic meningoencephalitis (naegleriasis). Parasitic worms (helminths) are macroparasites that can be seen by the naked eye. Worms live and feed in their living host, acquiring nutrients and shelter in the digestive tract or bloodstream of their host. They also manipulate the host's immune system by secreting immunomodulatory products which allows them to live in their host for years. Helminthiasis is the generalized term for parasitic worm infections, which typically involve roundworms , tapeworms , and flatworms . Algae are single-celled eukaryotes that are generally non-pathogenic. Green algae from the genus Prototheca lack chlorophyll and are known to cause the disease protothecosis in humans, dogs, cats, and cattle, typically involving the soil-associated species Prototheca wickerhami . Bacteria are single-celled prokaryotes that range in size from 0.15 and 700 μM. While the vast majority are either harmless or beneficial to their hosts, such as members of the human gut microbiome that support digestion, a small percentage are pathogenic and cause infectious diseases. Bacterial virulence factors include adherence factors to attach to host cells, invasion factors supporting entry into host cells, capsules to prevent opsonization and phagocytosis , toxins, and siderophores to acquire iron. The bacterial disease tuberculosis , primarily caused by Mycobacterium tuberculosis , has one of the highest disease burdens , killing 1.6 million people in 2021, mostly in Africa and Southeast Asia. Bacterial pneumonia is primarily caused by Streptococcus pneumoniae , Staphylococcus aureus , Klebsiella pneumoniae , and Haemophilus influenzae . Foodborne illnesses typically involve Campylobacter , Clostridium perfringens , Escherichia coli , Listeria monocytogenes , and Salmonella . Other infectious diseases caused by pathogenic bacteria include tetanus , typhoid fever , diphtheria , and leprosy . Fungi are eukaryotic organisms that can function as pathogens. There are approximately 300 known fungi that are pathogenic to humans, including Candida albicans , which is the most common cause of thrush , and Cryptococcus neoformans , which can cause a severe form of meningitis . Typical fungal spores are 4.7 μm long or smaller. Prions are misfolded proteins that transmit their abnormal folding pattern to other copies of the protein without using nucleic acids . Besides obtaining prions from others, these misfolded proteins arise from genetic differences, either due to family history or sporadic mutations. Plants uptake prions from contaminated soil and transport them into their stem and leaves, potentially transmitting the prions to herbivorous animals . Additionally, wood, rocks, plastic, glass, cement, stainless steel, and aluminum have been shown binding, retaining, and releasing prions, showcasing that the proteins resist environmental degradation. Prions are best known for causing transmissible spongiform encephalopathy (TSE) diseases like Creutzfeldt–Jakob disease (CJD), variant Creutzfeldt–Jakob disease (vCJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia (FFI), and kuru in humans. While prions are typically viewed as pathogens that cause protein amyloid fibers to accumulate into neurodegenerative plaques, Susan Lindquist led research showing that yeast use prions to pass on evolutionarily beneficial traits. Not to be confused with virusoids or viruses, viroids are the smallest known infectious pathogens. Viroids are small single-stranded, circular RNA that are only known to cause plant diseases, such as the potato spindle tuber viroid that affects various agricultural crops. Viroid RNA is not protected by a protein coat, and it does not encode any proteins, only acting as a ribozyme to catalyze other biochemical reactions. Viruses are generally between 20-200 nm in diameter. For survival and replication, viruses inject their genome into host cells, insert those genes into the host genome, and hijack the host's machinery to produce hundreds of new viruses until the cell bursts open to release them for additional infections. The lytic cycle describes this active state of rapidly killing hosts, while the lysogenic cycle describes potentially hundreds of years of dormancy while integrated in the host genome. Alongside the taxonomy organized by the International Committee on Taxonomy of Viruses (ICTV), the Baltimore classification separates viruses by seven classes of mRNA production: Protozoans are single-celled eukaryotes that feed on microorganisms and organic tissues. Many protozoans act as pathogenic parasites to cause diseases like malaria , amoebiasis , giardiasis , toxoplasmosis , cryptosporidiosis , trichomoniasis , Chagas disease , leishmaniasis , African trypanosomiasis (sleeping sickness), Acanthamoeba keratitis , and primary amoebic meningoencephalitis (naegleriasis). Parasitic worms (helminths) are macroparasites that can be seen by the naked eye. Worms live and feed in their living host, acquiring nutrients and shelter in the digestive tract or bloodstream of their host. They also manipulate the host's immune system by secreting immunomodulatory products which allows them to live in their host for years. Helminthiasis is the generalized term for parasitic worm infections, which typically involve roundworms , tapeworms , and flatworms . While bacteria are typically viewed as pathogens, they serve as hosts to bacteriophage viruses (commonly known as phages). The bacteriophage life cycle involves the viruses injecting their genome into bacterial cells, inserting those genes into the bacterial genome, and hijacking the bacteria's machinery to produce hundreds of new phages until the cell bursts open to release them for additional infections. Typically, bacteriophages are only capable of infecting a specific species or strain. Streptococcus pyogenes uses a Cas9 nuclease to cleave foreign DNA matching the Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR ) associated with bacteriophages, removing the viral genes to avoid infection. This mechanism has been modified for artificial CRISPR gene editing . Plants can play host to a wide range of pathogen types, including viruses, bacteria, fungi, nematodes, and even other plants. Notable plant viruses include the papaya ringspot virus , which has caused millions of dollars of damage to farmers in Hawaii and Southeast Asia, and the tobacco mosaic virus which caused scientist Martinus Beijerinck to coin the term "virus" in 1898. Bacterial plant pathogens cause leaf spots, blight, and rot in many plant species. The most common bacterial pathogens for plants are Pseudomonas syringae and Ralstonia solanacearum , which cause leaf browning and other issues in potatoes, tomatoes, and bananas. Fungi are another major pathogen type for plants. They can cause a wide variety of issues such as shorter plant height, growths or pits on tree trunks, root or seed rot, and leaf spots. Common and serious plant fungi include the rice blast fungus , Dutch elm disease , chestnut blight and the black knot and brown rot diseases of cherries, plums, and peaches. It is estimated that pathogenic fungi alone cause up to a 65% reduction in crop yield. Overall, plants have a wide array of pathogens and it has been estimated that only 3% of the disease caused by plant pathogens can be managed. Animals often get infected with many of the same or similar pathogens as humans including prions, viruses, bacteria, and fungi. While wild animals often get illnesses, the larger danger is for livestock animals. It is estimated that in rural settings, 90% or more of livestock deaths can be attributed to pathogens. Animal transmissible spongiform encephalopathy (TSEs) involving prions include bovine spongiform encephalopathy (mad cow disease), chronic wasting disease , scrapie , transmissible mink encephalopathy , feline spongiform encephalopathy , and ungulate spongiform encephalopathy. Other animal diseases include a variety of immunodeficiency disorders caused by viruses related to human immunodeficiency virus (HIV), such as BIV and FIV . Humans can be infected with many types of pathogens, including prions, viruses, bacteria, and fungi, causing symptoms like sneezing, coughing, fever, vomiting, and potentially lethal organ failure . While some symptoms are caused by the pathogenic infection, others are caused by the immune system's efforts to kill the pathogen, such as feverishly high body temperatures meant to denature pathogenic cells. While bacteria are typically viewed as pathogens, they serve as hosts to bacteriophage viruses (commonly known as phages). The bacteriophage life cycle involves the viruses injecting their genome into bacterial cells, inserting those genes into the bacterial genome, and hijacking the bacteria's machinery to produce hundreds of new phages until the cell bursts open to release them for additional infections. Typically, bacteriophages are only capable of infecting a specific species or strain. Streptococcus pyogenes uses a Cas9 nuclease to cleave foreign DNA matching the Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR ) associated with bacteriophages, removing the viral genes to avoid infection. This mechanism has been modified for artificial CRISPR gene editing . Plants can play host to a wide range of pathogen types, including viruses, bacteria, fungi, nematodes, and even other plants. Notable plant viruses include the papaya ringspot virus , which has caused millions of dollars of damage to farmers in Hawaii and Southeast Asia, and the tobacco mosaic virus which caused scientist Martinus Beijerinck to coin the term "virus" in 1898. Bacterial plant pathogens cause leaf spots, blight, and rot in many plant species. The most common bacterial pathogens for plants are Pseudomonas syringae and Ralstonia solanacearum , which cause leaf browning and other issues in potatoes, tomatoes, and bananas. Fungi are another major pathogen type for plants. They can cause a wide variety of issues such as shorter plant height, growths or pits on tree trunks, root or seed rot, and leaf spots. Common and serious plant fungi include the rice blast fungus , Dutch elm disease , chestnut blight and the black knot and brown rot diseases of cherries, plums, and peaches. It is estimated that pathogenic fungi alone cause up to a 65% reduction in crop yield. Overall, plants have a wide array of pathogens and it has been estimated that only 3% of the disease caused by plant pathogens can be managed. Animals often get infected with many of the same or similar pathogens as humans including prions, viruses, bacteria, and fungi. While wild animals often get illnesses, the larger danger is for livestock animals. It is estimated that in rural settings, 90% or more of livestock deaths can be attributed to pathogens. Animal transmissible spongiform encephalopathy (TSEs) involving prions include bovine spongiform encephalopathy (mad cow disease), chronic wasting disease , scrapie , transmissible mink encephalopathy , feline spongiform encephalopathy , and ungulate spongiform encephalopathy. Other animal diseases include a variety of immunodeficiency disorders caused by viruses related to human immunodeficiency virus (HIV), such as BIV and FIV . Humans can be infected with many types of pathogens, including prions, viruses, bacteria, and fungi, causing symptoms like sneezing, coughing, fever, vomiting, and potentially lethal organ failure . While some symptoms are caused by the pathogenic infection, others are caused by the immune system's efforts to kill the pathogen, such as feverishly high body temperatures meant to denature pathogenic cells. Despite many attempts, no therapy has been shown to halt the progression of prion diseases . A variety of prevention and treatment options exist for some viral pathogens. Vaccines are one common and effective preventive measure against a variety of viral pathogens. Vaccines prime the immune system of the host, so that when the potential host encounters the virus in the wild, the immune system can defend against infection quickly. Vaccines designed against viruses include annual influenza vaccines and the two-dose MMR vaccine against measles , mumps , and rubella . Vaccines are not available against the viruses responsible for HIV/AIDS , dengue , and chikungunya . Treatment of viral infections often involves treating the symptoms of the infection, rather than providing medication to combat the viral pathogen itself. Treating the symptoms of a viral infection gives the host immune system time to develop antibodies against the viral pathogen. However, for HIV, highly active antiretroviral therapy (HAART) is conducted to prevent the viral disease from progressing into AIDS as immune cells are lost. Much like viral pathogens, infection by certain bacterial pathogens can be prevented via vaccines. Vaccines against bacterial pathogens include the anthrax vaccine and pneumococcal vaccine . Many other bacterial pathogens lack vaccines as a preventive measure, but infection by these bacteria can often be treated or prevented with antibiotics . Common antibiotics include amoxicillin , ciprofloxacin , and doxycycline . Each antibiotic has different bacteria that it is effective against and has different mechanisms to kill that bacteria. For example, doxycycline inhibits the synthesis of new proteins in both gram-negative and gram-positive bacteria , which makes it a broad-spectrum antibiotic capable of killing most bacterial species. Due to misuse of antibiotics, such as prematurely ended prescriptions exposing bacteria to evolutionary pressure under sublethal doses, some bacterial pathogens have developed antibiotic resistance . For example, a genetically distinct strain of Staphylococcus aureus called MRSA is resistant to the commonly prescribed beta-lactam antibiotics . A 2013 report from the Centers for Disease Control and Prevention (CDC) estimated that in the United States, at least 2 million people get an antibiotic-resistant bacterial infection annually, with at least 23,000 of those patients dying from the infection. Due to their indispensability in combating bacteria, new antibiotics are required for medical care. One target for new antimicrobial medications involves inhibiting DNA methyltransferases , as these proteins control the levels of expression for other genes, such as those encoding virulence factors. Infection by fungal pathogens is treated with anti-fungal medication. Athlete's foot , jock itch , and ringworm are fungal skin infections that are treated with topical anti-fungal medications like clotrimazole . Infections involving the yeast species Candida albicans cause oral thrush and vaginal yeast infections . These internal infections can either be treated with anti-fungal creams or with oral medication. Common anti-fungal drugs for internal infections include the echinocandin family of drugs and fluconazole . While algae are commonly not thought of as pathogens, the genus Prototheca causes disease in humans . Treatment for protothecosis is currently under investigation, and there is no consistency in clinical treatment. Despite many attempts, no therapy has been shown to halt the progression of prion diseases . A variety of prevention and treatment options exist for some viral pathogens. Vaccines are one common and effective preventive measure against a variety of viral pathogens. Vaccines prime the immune system of the host, so that when the potential host encounters the virus in the wild, the immune system can defend against infection quickly. Vaccines designed against viruses include annual influenza vaccines and the two-dose MMR vaccine against measles , mumps , and rubella . Vaccines are not available against the viruses responsible for HIV/AIDS , dengue , and chikungunya . Treatment of viral infections often involves treating the symptoms of the infection, rather than providing medication to combat the viral pathogen itself. Treating the symptoms of a viral infection gives the host immune system time to develop antibodies against the viral pathogen. However, for HIV, highly active antiretroviral therapy (HAART) is conducted to prevent the viral disease from progressing into AIDS as immune cells are lost. Much like viral pathogens, infection by certain bacterial pathogens can be prevented via vaccines. Vaccines against bacterial pathogens include the anthrax vaccine and pneumococcal vaccine . Many other bacterial pathogens lack vaccines as a preventive measure, but infection by these bacteria can often be treated or prevented with antibiotics . Common antibiotics include amoxicillin , ciprofloxacin , and doxycycline . Each antibiotic has different bacteria that it is effective against and has different mechanisms to kill that bacteria. For example, doxycycline inhibits the synthesis of new proteins in both gram-negative and gram-positive bacteria , which makes it a broad-spectrum antibiotic capable of killing most bacterial species. Due to misuse of antibiotics, such as prematurely ended prescriptions exposing bacteria to evolutionary pressure under sublethal doses, some bacterial pathogens have developed antibiotic resistance . For example, a genetically distinct strain of Staphylococcus aureus called MRSA is resistant to the commonly prescribed beta-lactam antibiotics . A 2013 report from the Centers for Disease Control and Prevention (CDC) estimated that in the United States, at least 2 million people get an antibiotic-resistant bacterial infection annually, with at least 23,000 of those patients dying from the infection. Due to their indispensability in combating bacteria, new antibiotics are required for medical care. One target for new antimicrobial medications involves inhibiting DNA methyltransferases , as these proteins control the levels of expression for other genes, such as those encoding virulence factors. Infection by fungal pathogens is treated with anti-fungal medication. Athlete's foot , jock itch , and ringworm are fungal skin infections that are treated with topical anti-fungal medications like clotrimazole . Infections involving the yeast species Candida albicans cause oral thrush and vaginal yeast infections . These internal infections can either be treated with anti-fungal creams or with oral medication. Common anti-fungal drugs for internal infections include the echinocandin family of drugs and fluconazole . While algae are commonly not thought of as pathogens, the genus Prototheca causes disease in humans . Treatment for protothecosis is currently under investigation, and there is no consistency in clinical treatment. Many pathogens are capable of sexual interaction. Among pathogenic bacteria , sexual interaction occurs between cells of the same species by the process of genetic transformation . Transformation involves the transfer of DNA from a donor cell to a recipient cell and the integration of the donor DNA into the recipient genome through genetic recombination . The bacterial pathogens Helicobacter pylori , Haemophilus influenzae , Legionella pneumophila , Neisseria gonorrhoeae , and Streptococcus pneumoniae frequently undergo transformation to modify their genome for additional traits and evasion of host immune cells. Eukaryotic pathogens are often capable of sexual interaction by a process involving meiosis and fertilization . Meiosis involves the intimate pairing of homologous chromosomes and recombination between them. Examples of eukaryotic pathogens capable of sex include the protozoan parasites Plasmodium falciparum , Toxoplasma gondii , Trypanosoma brucei , Giardia intestinalis , and the fungi Aspergillus fumigatus , Candida albicans and Cryptococcus neoformans . Viruses may also undergo sexual interaction when two or more viral genomes enter the same host cell. This process involves pairing of homologous genomes and recombination between them by a process referred to as multiplicity reactivation. The herpes simplex virus , human immunodeficiency virus , and vaccinia virus undergo this form of sexual interaction. These processes of sexual recombination between homologous genomes supports repairs to genetic damage caused by environmental stressors and host immune systems.

Wiki

Chikungunya

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

Photophobia

Photophobia is a medical symptom of abnormal intolerance to visual perception of light . As a medical symptom, photophobia is not a morbid fear or phobia , but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical sensitivity of the eyes, though the term is sometimes additionally applied to abnormal or irrational fear of light, such as heliophobia . The term photophobia comes from the Greek φῶς ( phōs ), meaning "light", and φόβος ( phóbos ), meaning "fear". Patients may develop photophobia as a result of several different medical conditions, related to the eye , the nervous system , genetic, or other causes. Photophobia may manifest itself in an increased response to light starting at any step in the visual system , such as: Common causes of photophobia include migraine headaches , TMJ , cataracts , Sjögren syndrome , mild traumatic brain injury ( MTBI ), or severe ophthalmologic diseases such as uveitis or corneal abrasion . A more extensive list follows: Causes of photophobia relating directly to the eye itself include: Neurological causes for photophobia include:Causes of photophobia relating directly to the eye itself include:Neurological causes for photophobia include:Treatment for light sensitivity addresses the underlying cause, whether it be an eye, nervous system or other cause. If the triggering factor or underlying cause can be identified and treated, photophobia may disappear. Tinted glasses are sometimes used. People with photophobia may feel eye pain from even moderate levels of artificial light and avert their eyes from artificial light sources. Ambient levels of artificial light may also be intolerable to persons afflicted with photophobia such that they dim or remove the light source, or go into a dimmer lit room, such a one lit by refraction of light from outside the room. Alternatively, they may wear dark sunglasses , sunglasses designed to filter peripheral light, precision tinted glasses, and/or wide-brimmed sun hats or baseball caps . Some types of photophobia may be helped with the use of precision tinted lenses which block the green-to-blue end of the light spectrum without blurring or impeding vision. Other strategies for relieving photophobia include the use of tinted contact lenses and/or the use of prescription eye drops that constrict the pupil, thus reducing the amount of light entering the eye. Such strategies may be limited by the amount of light needed for proper vision under given conditions, however. Dilating drops may also help relieve eye pain from muscle spasms or seizures triggered by lighting/migraine, allowing a person to "ride out the migraine" in a dark or dim room. A paper by Stringham and Hammond, published in the Journal of Food Science , reviews studies of effects of consuming Lutein and Zeaxanthin on visual performance, and notes a decrease in sensitivity to glare. Photophobia may preclude or limit a person from working in places where lighting is used, unless the person is able to obtain a reasonable accommodation like being allowed to wear tinted glasses. Some people with photophobia may thereby be better able to work at night or be more easily accommodated in the workplace at night. Outdoor night lighting may be equally offensive for persons with photophobia, however, given the wide variety of bright lighting used for illuminating residential, commercial and industrial areas, such as LED (light-emitting diode) lamps. The increasing popularity of "overpoweringly intense" LED headlights being used on " pickups and S.U.V.s " has prompted more frequent reports of photophobia among motorists, cyclists, and pedestrians.

Wiki

Chikungunya

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

Vaccine

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylactic (to prevent or alleviate the effects of a future infection by a natural or "wild" pathogen ), or therapeutic (to fight a disease that has already occurred, such as cancer ). Some vaccines offer full sterilizing immunity , in which infection is prevented completely. The administration of vaccines is called vaccination . Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the restriction of diseases such as polio , measles , and tetanus from much of the world. The World Health Organization (WHO) reports that licensed vaccines are currently available for twenty-five different preventable infections . The first recorded use of inoculation to prevent smallpox occurred in the 16th century in China, with the earliest hints of the practice in China coming during the 10th century. It was also the first disease for which a vaccine was produced. The folk practice of inoculation against smallpox was brought from Turkey to Britain in 1721 by Lady Mary Wortley Montagu . The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Edward Jenner (who both developed the concept of vaccines and created the first vaccine) to denote cowpox . He used the phrase in 1798 for the long title of his Inquiry into the Variolae vaccinae Known as the Cow Pox , in which he described the protective effect of cowpox against smallpox. In 1881, to honor Jenner, Louis Pasteur proposed that the terms should be extended to cover the new protective inoculations then being developed. The science of vaccine development and production is termed vaccinology .There is overwhelming scientific consensus that vaccines are a very safe and effective way to fight and eradicate infectious diseases. The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the virulent version of an agent is encountered, the body recognizes the protein coat on the agent, and thus is prepared to respond, by first neutralizing the target agent before it can enter cells, and secondly by recognizing and destroying infected cells before that agent can multiply to vast numbers. Limitations to their effectiveness, nevertheless, exist. Sometimes, protection fails for vaccine-related reasons such as failures in vaccine attenuation, vaccination regimens or administration. Failure may also occur for host-related reasons if the host's immune system does not respond adequately or at all. Host-related lack of response occurs in an estimated 2-10% of individuals, due to factors including genetics, immune status, age, health and nutritional status. One type of primary immunodeficiency disorder resulting in genetic failure is X-linked agammaglobulinemia , in which the absence of an enzyme essential for B cell development prevents the host's immune system from generating antibodies to a pathogen . Host–pathogen interactions and responses to infection are dynamic processes involving multiple pathways in the immune system. A host does not develop antibodies instantaneously: while the body's innate immunity may be activated in as little as twelve hours, adaptive immunity can take 1–2 weeks to fully develop. During that time, the host can still become infected. Once antibodies are produced, they may promote immunity in any of several ways, depending on the class of antibodies involved. Their success in clearing or inactivating a pathogen will depend on the amount of antibodies produced and on the extent to which those antibodies are effective at countering the strain of the pathogen involved, since different strains may be differently susceptible to a given immune reaction. In some cases vaccines may result in partial immune protection (in which immunity is less than 100% effective but still reduces risk of infection) or in temporary immune protection (in which immunity wanes over time) rather than full or permanent immunity. They can still raise the reinfection threshold for the population as a whole and make a substantial impact. They can also mitigate the severity of infection, resulting in a lower mortality rate , lower morbidity , faster recovery from illness, and a wide range of other effects. Those who are older often display less of a response than those who are younger, a pattern known as Immunosenescence . Adjuvants commonly are used to boost immune response, particularly for older people whose immune response to a simple vaccine may have weakened. The efficacy or performance of the vaccine is dependent on several factors: the disease itself (for some diseases vaccination performs better than for others) the strain of vaccine (some vaccines are specific to, or at least most effective against, particular strains of the disease) whether the vaccination schedule has been properly observed. idiosyncratic response to vaccination; some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly. assorted factors such as ethnicity, age, or genetic predisposition. If a vaccinated individual does develop the disease vaccinated against ( breakthrough infection ), the disease is likely to be less virulent than in unvaccinated cases. Important considerations in an effective vaccination program: careful modeling to anticipate the effect that an immunization campaign will have on the epidemiology of the disease in the medium to long term ongoing surveillance for the relevant disease following introduction of a new vaccine maintenance of high immunization rates, even when a disease has become rare In 1958, there were 763,094 cases of measles in the United States; 552 deaths resulted. After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56). In early 2008, there were 64 suspected cases of measles. Fifty-four of those infections were associated with importation from another country, although only thirteen percent were actually acquired outside the United States; 63 of the 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated. Vaccines led to the eradication of smallpox , one of the most contagious and deadly diseases in humans. Other diseases such as rubella, polio , measles, mumps, chickenpox , and typhoid are nowhere near as common as they were a hundred years ago thanks to widespread vaccination programs. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity . Polio, which is transmitted only among humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan). However, the difficulty of reaching all children, cultural misunderstandings, and disinformation have caused the anticipated eradication date to be missed several times. Vaccines also help prevent the development of antibiotic resistance. For example, by greatly reducing the incidence of pneumonia caused by Streptococcus pneumoniae , vaccine programs have greatly reduced the prevalence of infections resistant to penicillin or other first-line antibiotics. The measles vaccine is estimated to prevent a million deaths every year. Vaccinations given to children, adolescents, or adults are generally safe. Adverse effects, if any, are generally mild. The rate of side effects depends on the vaccine in question. Some common side effects include fever, pain around the injection site, and muscle aches. Additionally, some individuals may be allergic to ingredients in the vaccine. MMR vaccine is rarely associated with febrile seizures . Host-("vaccinee")-related determinants that render a person susceptible to infection, such as genetics , health status (underlying disease, nutrition, pregnancy, sensitivities or allergies ), immune competence , age, and economic impact or cultural environment can be primary or secondary factors affecting the severity of infection and response to a vaccine. Elderly (above age 60), allergen-hypersensitive , and obese people have susceptibility to compromised immunogenicity , which prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive booster vaccinations to limit virus transmission . Severe side effects are extremely rare. Varicella vaccine is rarely associated with complications in immunodeficient individuals, and rotavirus vaccines are moderately associated with intussusception . At least 19 countries have no-fault compensation programs to provide compensation for those with severe adverse effects of vaccination. The United States' program is known as the National Childhood Vaccine Injury Act , and the United Kingdom employs the Vaccine Damage Payment .Vaccinations given to children, adolescents, or adults are generally safe. Adverse effects, if any, are generally mild. The rate of side effects depends on the vaccine in question. Some common side effects include fever, pain around the injection site, and muscle aches. Additionally, some individuals may be allergic to ingredients in the vaccine. MMR vaccine is rarely associated with febrile seizures . Host-("vaccinee")-related determinants that render a person susceptible to infection, such as genetics , health status (underlying disease, nutrition, pregnancy, sensitivities or allergies ), immune competence , age, and economic impact or cultural environment can be primary or secondary factors affecting the severity of infection and response to a vaccine. Elderly (above age 60), allergen-hypersensitive , and obese people have susceptibility to compromised immunogenicity , which prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive booster vaccinations to limit virus transmission . Severe side effects are extremely rare. Varicella vaccine is rarely associated with complications in immunodeficient individuals, and rotavirus vaccines are moderately associated with intussusception . At least 19 countries have no-fault compensation programs to provide compensation for those with severe adverse effects of vaccination. The United States' program is known as the National Childhood Vaccine Injury Act , and the United Kingdom employs the Vaccine Damage Payment .Vaccines typically contain attenuated, inactivated or dead organisms or purified products derived from them. There are several types of vaccines in use. These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response. Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever , measles , mumps , and rubella , and the bacterial disease typhoid . The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain but contains a virulently modified strain called " BCG " used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain Yersinia pestis EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease. Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation – "ghosts", with intact but empty bacterial cell envelopes. They are considered an intermediate phase between the inactivated and attenuated vaccines. Examples include IPV ( polio vaccine ), hepatitis A vaccine , rabies vaccine and most influenza vaccines . Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria . Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites. Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a subunit vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against hepatitis B , which is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients but now produced by recombination of the viral genes into yeast ). Another example is edible algae vaccines , such as the virus-like particle (VLP) vaccine against human papillomavirus (HPV), which is composed of the viral major capsid protein. Another example is the hemagglutinin and neuraminidase subunits of the influenza virus. A subunit vaccine is being used for plague immunization. Certain bacteria have a polysaccharide outer coat that is poorly immunogenic . By linking these outer coats to proteins (e.g., toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine . Outer membrane vesicles (OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for serotype B meningococcal disease . Heterologous vaccines also known as "Jennerian vaccines", are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against tuberculosis . Genetic vaccines are based on the principle of uptake of a nucleic acid into cells, whereupon a protein is produced according to the nucleic acid template. This protein is usually the immunodominant antigen of the pathogen or a surface protein that enables the formation of neutralizing antibodies. The subgroup of genetic vaccines encompass viral vector vaccines, RNA vaccines and DNA vaccines. [ citation needed ] Viral vector vaccines use a safe virus to insert pathogen genes in the body to produce specific antigens , such as surface proteins , to stimulate an immune response . An mRNA vaccine (or RNA vaccine ) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles . Among the COVID-19 vaccines are a number of RNA vaccines to combat the COVID-19 pandemic and some have been approved or have received emergency use authorization in some countries. For example, the Pfizer-BioNTech vaccine and Moderna mRNA vaccine are approved for use in adults and children in the US. A DNA vaccine uses a DNA plasmid (pDNA)) that encodes for an antigenic protein originating from the pathogen upon which the vaccine will be targeted. pDNA is inexpensive, stable, and relatively safe, making it an excellent option for vaccine delivery. This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture. Many innovative vaccines are also in development and use. While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever , measles , mumps , and rubella , and the bacterial disease typhoid . The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain but contains a virulently modified strain called " BCG " used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain Yersinia pestis EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease. Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation – "ghosts", with intact but empty bacterial cell envelopes. They are considered an intermediate phase between the inactivated and attenuated vaccines. Examples include IPV ( polio vaccine ), hepatitis A vaccine , rabies vaccine and most influenza vaccines . Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria . Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites. Rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a subunit vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against hepatitis B , which is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients but now produced by recombination of the viral genes into yeast ). Another example is edible algae vaccines , such as the virus-like particle (VLP) vaccine against human papillomavirus (HPV), which is composed of the viral major capsid protein. Another example is the hemagglutinin and neuraminidase subunits of the influenza virus. A subunit vaccine is being used for plague immunization. Certain bacteria have a polysaccharide outer coat that is poorly immunogenic . By linking these outer coats to proteins (e.g., toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine . Outer membrane vesicles (OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for serotype B meningococcal disease . Heterologous vaccines also known as "Jennerian vaccines", are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against tuberculosis . Genetic vaccines are based on the principle of uptake of a nucleic acid into cells, whereupon a protein is produced according to the nucleic acid template. This protein is usually the immunodominant antigen of the pathogen or a surface protein that enables the formation of neutralizing antibodies. The subgroup of genetic vaccines encompass viral vector vaccines, RNA vaccines and DNA vaccines. [ citation needed ] Viral vector vaccines use a safe virus to insert pathogen genes in the body to produce specific antigens , such as surface proteins , to stimulate an immune response . An mRNA vaccine (or RNA vaccine ) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles . Among the COVID-19 vaccines are a number of RNA vaccines to combat the COVID-19 pandemic and some have been approved or have received emergency use authorization in some countries. For example, the Pfizer-BioNTech vaccine and Moderna mRNA vaccine are approved for use in adults and children in the US. A DNA vaccine uses a DNA plasmid (pDNA)) that encodes for an antigenic protein originating from the pathogen upon which the vaccine will be targeted. pDNA is inexpensive, stable, and relatively safe, making it an excellent option for vaccine delivery. This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture. Viral vector vaccines use a safe virus to insert pathogen genes in the body to produce specific antigens , such as surface proteins , to stimulate an immune response . An mRNA vaccine (or RNA vaccine ) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid nanoparticles . Among the COVID-19 vaccines are a number of RNA vaccines to combat the COVID-19 pandemic and some have been approved or have received emergency use authorization in some countries. For example, the Pfizer-BioNTech vaccine and Moderna mRNA vaccine are approved for use in adults and children in the US. A DNA vaccine uses a DNA plasmid (pDNA)) that encodes for an antigenic protein originating from the pathogen upon which the vaccine will be targeted. pDNA is inexpensive, stable, and relatively safe, making it an excellent option for vaccine delivery. This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture. Many innovative vaccines are also in development and use. While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.Vaccines may be monovalent (also called univalent ) or multivalent (also called polyvalent ). A monovalent vaccine is designed to immunize against a single antigen or single microorganism. A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., bivalent , trivalent , or tetravalent/quadrivalent ). In certain cases, a monovalent vaccine may be preferable for rapidly developing a strong immune response. When two or more vaccines are mixed in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first [ when? ] noted in the trivalent Sabin polio vaccine , where the amount of serotype 2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype 1 and 3 viruses in the vaccine. It was also noted in a 2001 study to be a problem with dengue vaccines, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, -2 and -4 serotypes. When two or more vaccines are mixed in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first [ when? ] noted in the trivalent Sabin polio vaccine , where the amount of serotype 2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype 1 and 3 viruses in the vaccine. It was also noted in a 2001 study to be a problem with dengue vaccines, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, -2 and -4 serotypes. Vaccines typically contain one or more adjuvants , used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum . This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster. In the preparation for the 1990 Persian Gulf campaign, the whole cell pertussis vaccine was used as an adjuvant for anthrax vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent. Vaccines may also contain preservatives to prevent contamination with bacteria or fungi . Until recent years, the preservative thiomersal ( a.k.a. Thimerosal in the US and Japan) was used in many vaccines that did not contain live viruses. As of 2005, the only childhood vaccine in the U.S. that contains thiomersal in greater than trace amounts is the influenza vaccine, which is currently recommended only for children with certain risk factors. Single-dose influenza vaccines supplied in the UK do not list thiomersal in the ingredients. Preservatives may be used at various stages of the production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole. Many vaccines need preservatives to prevent serious adverse effects such as Staphylococcus infection, which in one 1928 incident killed 12 of 21 children inoculated with a diphtheria vaccine that lacked a preservative. Several preservatives are available, including thiomersal, phenoxyethanol , and formaldehyde . Thiomersal is more effective against bacteria, has a better shelf-life, and improves vaccine stability, potency, and safety; but, in the U.S., the European Union , and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its mercury content. Although controversial claims have been made that thiomersal contributes to autism , no convincing scientific evidence supports these claims. Furthermore, a 10–11-year study of 657,461 children found that the MMR vaccine does not cause autism and actually reduced the risk of autism by seven percent. Beside the active vaccine itself, the following excipients and residual manufacturing compounds are present or may be present in vaccine preparations: Vaccines typically contain one or more adjuvants , used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum . This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster. In the preparation for the 1990 Persian Gulf campaign, the whole cell pertussis vaccine was used as an adjuvant for anthrax vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent. Vaccines may also contain preservatives to prevent contamination with bacteria or fungi . Until recent years, the preservative thiomersal ( a.k.a. Thimerosal in the US and Japan) was used in many vaccines that did not contain live viruses. As of 2005, the only childhood vaccine in the U.S. that contains thiomersal in greater than trace amounts is the influenza vaccine, which is currently recommended only for children with certain risk factors. Single-dose influenza vaccines supplied in the UK do not list thiomersal in the ingredients. Preservatives may be used at various stages of the production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole. Many vaccines need preservatives to prevent serious adverse effects such as Staphylococcus infection, which in one 1928 incident killed 12 of 21 children inoculated with a diphtheria vaccine that lacked a preservative. Several preservatives are available, including thiomersal, phenoxyethanol , and formaldehyde . Thiomersal is more effective against bacteria, has a better shelf-life, and improves vaccine stability, potency, and safety; but, in the U.S., the European Union , and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its mercury content. Although controversial claims have been made that thiomersal contributes to autism , no convincing scientific evidence supports these claims. Furthermore, a 10–11-year study of 657,461 children found that the MMR vaccine does not cause autism and actually reduced the risk of autism by seven percent. Beside the active vaccine itself, the following excipients and residual manufacturing compounds are present or may be present in vaccine preparations: Various fairly standardized abbreviations for vaccine names have developed, although the standardization is by no means centralized or global. For example, the vaccine names used in the United States have well-established abbreviations that are also widely known and used elsewhere. An extensive list of them provided in a sortable table and freely accessible is available at a US Centers for Disease Control and Prevention web page. The page explains that "The abbreviations [in] this table (Column 3) were standardized jointly by staff of the Centers for Disease Control and Prevention, ACIP Work Groups, the editor of the Morbidity and Mortality Weekly Report (MMWR), the editor of Epidemiology and Prevention of Vaccine-Preventable Diseases (the Pink Book), ACIP members, and liaison organizations to the ACIP." Some examples are " DTaP " for diphtheria and tetanus toxoids and acellular pertussis vaccine, "DT" for diphtheria and tetanus toxoids, and "Td" for tetanus and diphtheria toxoids. At its page on tetanus vaccination, the CDC further explains that "Upper-case letters in these abbreviations denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and pertussis (P) vaccine. Lower-case "d" and "p" denote reduced doses of diphtheria and pertussis used in the adolescent/adult-formulations. The 'a' in DTaP and Tdap stands for 'acellular', meaning that the pertussis component contains only a part of the pertussis organism." Another list of established vaccine abbreviations is at the CDC's page called "Vaccine Acronyms and Abbreviations", with abbreviations used on U.S. immunization records. The United States Adopted Name system has some conventions for the word order of vaccine names, placing head nouns first and adjectives postpositively . This is why the USAN for " OPV " is "poliovirus vaccine live oral" rather than "oral poliovirus vaccine".A vaccine licensure occurs after the successful conclusion of the development cycle and further the clinical trials and other programs involved through Phases I–III demonstrating safety, immunoactivity, immunogenetic safety at a given specific dose, proven effectiveness in preventing infection for target populations, and enduring preventive effect (time endurance or need for revaccination must be estimated). Because preventive vaccines are predominantly evaluated in healthy population cohorts and distributed among the general population, a high standard of safety is required. As part of a multinational licensing of a vaccine, the World Health Organization Expert Committee on Biological Standardization developed guidelines of international standards for manufacturing and quality control of vaccines, a process intended as a platform for national regulatory agencies to apply for their own licensing process. Vaccine manufacturers do not receive licensing until a complete clinical cycle of development and trials proves the vaccine is safe and has long-term effectiveness, following scientific review by a multinational or national regulatory organization, such as the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA). Upon developing countries adopting WHO guidelines for vaccine development and licensure, each country has its own responsibility to issue a national licensure, and to manage, deploy, and monitor the vaccine throughout its use in each nation. Building trust and acceptance of a licensed vaccine among the public is a task of communication by governments and healthcare personnel to ensure a vaccination campaign proceeds smoothly, saves lives, and enables economic recovery. When a vaccine is licensed, it will initially be in limited supply due to variable manufacturing, distribution, and logistical factors, requiring an allocation plan for the limited supply and which population segments should be prioritized to first receive the vaccine. Vaccines developed for multinational distribution via the United Nations Children's Fund (UNICEF) require pre-qualification by the WHO to ensure international standards of quality, safety, immunogenicity, and efficacy for adoption by numerous countries. The process requires manufacturing consistency at WHO-contracted laboratories following Good Manufacturing Practice (GMP). When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting postmarketing surveillance , including records for adverse events after the vaccination program. The WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight. Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries. In the European Union (EU), vaccines for pandemic pathogens, such as seasonal influenza , are licensed EU-wide where all the member states comply ("centralized"), are licensed for only some member states ("decentralized"), or are licensed on an individual national level. Generally, all EU states follow regulatory guidance and clinical programs defined by the European Committee for Medicinal Products for Human Use (CHMP), a scientific panel of the European Medicines Agency (EMA) responsible for vaccine licensure. The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution. Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for the approval process for prescription drugs . If successful through the stages of clinical development, the vaccine licensing process is followed by a Biologics License Application which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) and comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have a compliant description to enable health care providers' definition of vaccine-specific use, including its possible risks, to communicate and deliver the vaccine to the public. After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step. Drugs Controller General of India is the head of department of the Central Drugs Standard Control Organization of the Government of India responsible for approval of licences of specified categories of drugs such as vaccines AND others like blood and blood products, IV fluids, and sera in India. Until a vaccine is in use for the general population, all potential adverse events from the vaccine may not be known, requiring manufacturers to conduct Phase IV studies for postmarketing surveillance of the vaccine while it is used widely in the public. The WHO works with UN member states to implement post-licensing surveillance. The FDA relies on a Vaccine Adverse Event Reporting System to monitor safety concerns about a vaccine throughout its use in the American public. Vaccines developed for multinational distribution via the United Nations Children's Fund (UNICEF) require pre-qualification by the WHO to ensure international standards of quality, safety, immunogenicity, and efficacy for adoption by numerous countries. The process requires manufacturing consistency at WHO-contracted laboratories following Good Manufacturing Practice (GMP). When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting postmarketing surveillance , including records for adverse events after the vaccination program. The WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight. Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries. In the European Union (EU), vaccines for pandemic pathogens, such as seasonal influenza , are licensed EU-wide where all the member states comply ("centralized"), are licensed for only some member states ("decentralized"), or are licensed on an individual national level. Generally, all EU states follow regulatory guidance and clinical programs defined by the European Committee for Medicinal Products for Human Use (CHMP), a scientific panel of the European Medicines Agency (EMA) responsible for vaccine licensure. The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution. Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for the approval process for prescription drugs . If successful through the stages of clinical development, the vaccine licensing process is followed by a Biologics License Application which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) and comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have a compliant description to enable health care providers' definition of vaccine-specific use, including its possible risks, to communicate and deliver the vaccine to the public. After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step. Drugs Controller General of India is the head of department of the Central Drugs Standard Control Organization of the Government of India responsible for approval of licences of specified categories of drugs such as vaccines AND others like blood and blood products, IV fluids, and sera in India. Until a vaccine is in use for the general population, all potential adverse events from the vaccine may not be known, requiring manufacturers to conduct Phase IV studies for postmarketing surveillance of the vaccine while it is used widely in the public. The WHO works with UN member states to implement post-licensing surveillance. The FDA relies on a Vaccine Adverse Event Reporting System to monitor safety concerns about a vaccine throughout its use in the American public. In order to provide the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional "booster" shots often required to achieve "full immunity". This has led to the development of complex vaccination schedules. Global recommendations of vaccination schedule are issued by Strategic Advisory Group of Experts and will be further translated by advisory committee at the country level with considering of local factors such as disease epidemiology, acceptability of vaccination, equity in local populations, and programmatic and financial constraint. In the United States, the Advisory Committee on Immunization Practices , which recommends schedule additions for the Centers for Disease Control and Prevention , recommends routine vaccination of children against hepatitis A , hepatitis B , polio, mumps, measles, rubella, diphtheria , pertussis , tetanus , HiB , chickenpox, rotavirus , influenza , meningococcal disease and pneumonia . The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. To combat declining compliance rates, various notification systems have been instituted and many combination injections are now marketed (e.g., Pentavalent vaccine and MMRV vaccine ), which protect against multiple diseases. Besides recommendations for infant vaccinations and boosters, many specific vaccines are recommended for other ages or for repeated injections throughout life – most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. The human papillomavirus vaccine is recommended in the U.S. (as of 2011) and UK (as of 2009). Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against shingles , a disease caused by the chickenpox virus, which usually affects the elderly. Scheduling and dosing of a vaccination may be tailored to the level of immunocompetence of an individual and to optimize population-wide deployment of a vaccine when it supply is limited, e.g. in the setting of a pandemic.One challenge in vaccine development is economic: Many of the diseases most demanding a vaccine, including HIV , malaria and tuberculosis, exist principally in poor countries. Pharmaceutical firms and biotechnology companies have little incentive to develop vaccines for these diseases because there is little revenue potential. Even in more affluent countries, financial returns are usually minimal and the financial and other risks are great. Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations. Many vaccines have been highly cost effective and beneficial for public health . The number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools may be due to government mandates and support, rather than economic incentive. According to the World Health Organization, the biggest barrier to vaccine production in less developed countries has not been patents , but the substantial financial, infrastructure , and workforce requirements needed for market entry. Vaccines are complex mixtures of biological compounds, and unlike the case for prescription drugs , there are no true generic vaccines . The vaccine produced by a new facility must undergo complete clinical testing for safety and efficacy by the manufacturer. For most vaccines, specific processes in technology are patented. These can be circumvented by alternative manufacturing methods, but this required R&D infrastructure and a suitably skilled workforce. In the case of a few relatively new vaccines, such as the human papillomavirus vaccine, the patents may impose an additional barrier. When increased production of vaccines was urgently needed during the COVID-19 pandemic in 2021, the World Trade Organization and governments around the world evaluated whether to waive intellectual property rights and patents on COVID-19 vaccines , which would "eliminate all potential barriers to the timely access of affordable COVID-19 medical products, including vaccines and medicines, and scale up the manufacturing and supply of essential medical products". According to the World Health Organization, the biggest barrier to vaccine production in less developed countries has not been patents , but the substantial financial, infrastructure , and workforce requirements needed for market entry. Vaccines are complex mixtures of biological compounds, and unlike the case for prescription drugs , there are no true generic vaccines . The vaccine produced by a new facility must undergo complete clinical testing for safety and efficacy by the manufacturer. For most vaccines, specific processes in technology are patented. These can be circumvented by alternative manufacturing methods, but this required R&D infrastructure and a suitably skilled workforce. In the case of a few relatively new vaccines, such as the human papillomavirus vaccine, the patents may impose an additional barrier. When increased production of vaccines was urgently needed during the COVID-19 pandemic in 2021, the World Trade Organization and governments around the world evaluated whether to waive intellectual property rights and patents on COVID-19 vaccines , which would "eliminate all potential barriers to the timely access of affordable COVID-19 medical products, including vaccines and medicines, and scale up the manufacturing and supply of essential medical products". Vaccine production is fundamentally different from other kinds of manufacturing – including regular pharmaceutical manufacturing – in that vaccines are intended to be administered to millions of people of whom the vast majority are perfectly healthy. This fact drives an extraordinarily rigorous production process with strict compliance requirements that go far beyond what is required of other products. Depending upon the antigen, it can cost anywhere from US$50 to $500 million to build a vaccine production facility, which requires highly specialized equipment, clean rooms , and containment rooms. There is a global scarcity of personnel with the right combination of skills, expertise, knowledge, competence and personality to staff vaccine production lines. With the notable exceptions of Brazil, China, and India, many developing countries' educational systems are unable to provide enough qualified candidates, and vaccine makers based in such countries must hire expatriate personnel to keep production going. Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either on primary cells such as chicken eggs (e.g., for influenza) or on continuous cell lines such as cultured human cells (e.g., for hepatitis A ). Bacteria are grown in bioreactors (e.g., Haemophilus influenzae type b). Likewise, a recombinant protein derived from the viruses or bacteria can be generated in yeast, bacteria, or cell cultures. After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response to the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials. Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved. The final stage in vaccine manufacture before distribution is fill and finish , which is the process of filling vials with vaccines and packaging them for distribution. Although this is a conceptually simple part of the vaccine manufacture process, it is often a bottleneck in the process of distributing and administering vaccines. Vaccine production techniques are evolving. Cultured mammalian cells are expected to become increasingly important, compared to conventional options such as chicken eggs, due to greater productivity and low incidence of problems with contamination. Recombination technology that produces genetically detoxified vaccines is expected to grow in popularity for the production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce the quantities of antigens they contain, and thereby decrease undesirable interactions, by using pathogen-associated molecular patterns . The companies with the highest market share in vaccine production are Merck , Sanofi , GlaxoSmithKline , Pfizer and Novartis , with 70% of vaccine sales concentrated in the EU or US (2013). : 42 Vaccine manufacturing plants require large capital investments ($50 million up to $300 million) and may take between 4 and 6 years to construct, with the full process of vaccine development taking between 10 and 15 years. : 43 Manufacturing in developing countries is playing an increasing role in supplying these countries, specifically with regards to older vaccines and in Brazil, India and China. : 47 The manufacturers in India are the most advanced in the developing world and include the Serum Institute of India , one of the largest producers of vaccines by number of doses and an innovator in processes, recently improving efficiency of producing the measles vaccine by 10 to 20-fold, due to switching to a MRC-5 cell culture instead of chicken eggs. : 48 China's manufacturing capabilities are focused on supplying their own domestic need, with Sinopharm (CNPGC) alone providing over 85% of the doses for 14 different vaccines in China. : 48 Brazil is approaching the point of supplying its own domestic needs using technology transferred from the developed world. : 49The companies with the highest market share in vaccine production are Merck , Sanofi , GlaxoSmithKline , Pfizer and Novartis , with 70% of vaccine sales concentrated in the EU or US (2013). : 42 Vaccine manufacturing plants require large capital investments ($50 million up to $300 million) and may take between 4 and 6 years to construct, with the full process of vaccine development taking between 10 and 15 years. : 43 Manufacturing in developing countries is playing an increasing role in supplying these countries, specifically with regards to older vaccines and in Brazil, India and China. : 47 The manufacturers in India are the most advanced in the developing world and include the Serum Institute of India , one of the largest producers of vaccines by number of doses and an innovator in processes, recently improving efficiency of producing the measles vaccine by 10 to 20-fold, due to switching to a MRC-5 cell culture instead of chicken eggs. : 48 China's manufacturing capabilities are focused on supplying their own domestic need, with Sinopharm (CNPGC) alone providing over 85% of the doses for 14 different vaccines in China. : 48 Brazil is approaching the point of supplying its own domestic needs using technology transferred from the developed world. : 49One of the most common methods of delivering vaccines into the human body is injection . The development of new delivery systems raises the hope of vaccines that are safer and more efficient to deliver and administer. Lines of research include liposomes and ISCOM (immune stimulating complex). Notable developments in vaccine delivery technologies have included oral vaccines. Early attempts to apply oral vaccines showed varying degrees of promise, beginning early in the 20th century, at a time when the very possibility of an effective oral antibacterial vaccine was controversial. By the 1930s there was increasing interest in the prophylactic value of an oral typhoid fever vaccine for example. An oral polio vaccine turned out to be effective when vaccinations were administered by volunteer staff without formal training; the results also demonstrated increased ease and efficiency of administering the vaccines. Effective oral vaccines have many advantages; for example, there is no risk of blood contamination. Vaccines intended for oral administration need not be liquid, and as solids, they commonly are more stable and less prone to damage or spoilage by freezing in transport and storage. Such stability reduces the need for a " cold chain ": the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, may decrease costs of vaccines. A microneedle approach, which is still in stages of development, uses "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin". An experimental needle-free vaccine delivery system is undergoing animal testing. A stamp-size patch similar to an adhesive bandage contains about 20,000 microscopic projections per square cm. This dermal administration potentially increases the effectiveness of vaccination, while requiring less vaccine than injection. Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans. Both animals kept as pets and animals raised as livestock are routinely vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control rabies in raccoons . Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include canine distemper , canine parvovirus , infectious canine hepatitis , adenovirus-2 , leptospirosis , Bordetella , canine parainfluenza virus , and Lyme disease , among others. Cases of veterinary vaccines used in humans have been documented, whether intentional or accidental, with some cases of resultant illness, most notably with brucellosis . However, the reporting of such cases is rare and very little has been studied about the safety and results of such practices. With the advent of aerosol vaccination in veterinary clinics, human exposure to pathogens not naturally carried in humans, such as Bordetella bronchiseptica , has likely increased in recent years. In some cases, most notably rabies , the parallel veterinary vaccine against a pathogen may be as much as orders of magnitude more economical than the human one. DIVA (Differentiation of Infected from Vaccinated Animals), also known as SIVA (Segregation of Infected from Vaccinated Animals) vaccines, make it possible to differentiate between infected and vaccinated animals. DIVA vaccines carry at least one epitope less than the equivalent wild microorganism. An accompanying diagnostic test that detects the antibody against that epitope assists in identifying whether the animal has been vaccinated or not. [ citation needed ] The first DIVA vaccines (formerly termed marker vaccines and since 1999 coined as DIVA vaccines) and companion diagnostic tests were developed by J. T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands. They found that some existing vaccines against pseudorabies (also termed Aujeszky's disease) had deletions in their viral genome (among which was the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an ELISA that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed. Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus 1 infections have been developed. The DIVA strategy has been applied in various countries to successfully eradicate pseudorabies virus from those countries. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and, subsequently, the infected pigs were removed from the population. Bovine herpesvirus 1 DIVA vaccines are also widely used in practice. [ citation needed ] Considerable efforts are ongoing to apply the DIVA principle to a wide range of infectious diseases, such as classical swine fever, avian influenza, Actinobacillus pleuropneumonia and Salmonella infections in pigs. DIVA (Differentiation of Infected from Vaccinated Animals), also known as SIVA (Segregation of Infected from Vaccinated Animals) vaccines, make it possible to differentiate between infected and vaccinated animals. DIVA vaccines carry at least one epitope less than the equivalent wild microorganism. An accompanying diagnostic test that detects the antibody against that epitope assists in identifying whether the animal has been vaccinated or not. [ citation needed ] The first DIVA vaccines (formerly termed marker vaccines and since 1999 coined as DIVA vaccines) and companion diagnostic tests were developed by J. T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands. They found that some existing vaccines against pseudorabies (also termed Aujeszky's disease) had deletions in their viral genome (among which was the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an ELISA that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed. Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus 1 infections have been developed. The DIVA strategy has been applied in various countries to successfully eradicate pseudorabies virus from those countries. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and, subsequently, the infected pigs were removed from the population. Bovine herpesvirus 1 DIVA vaccines are also widely used in practice. [ citation needed ] Considerable efforts are ongoing to apply the DIVA principle to a wide range of infectious diseases, such as classical swine fever, avian influenza, Actinobacillus pleuropneumonia and Salmonella infections in pigs. Prior to the introduction of vaccination with material from cases of cowpox (heterotypic immunisation), smallpox could be prevented by deliberate variolation with smallpox virus. The earliest hints of the practice of variolation for smallpox in China come during the tenth century. [ further explanation needed ] The Chinese also practiced the oldest documented use of variolation, dating back to the fifteenth century. They implemented a method of "nasal insufflation " administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China. : 60 Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers . In France, Voltaire reports that the Chinese have practiced variolation "these hundred years". Mary Wortley Montagu , who had witnessed variolation in Turkey, had her four-year-old daughter variolated in the presence of physicians of the Royal Court in 1721 upon her return to England. Later on that year, Charles Maitland conducted an experimental variolation of six prisoners in Newgate Prison in London. The experiment was a success, and soon variolation was drawing attention from the royal family, who helped promote the procedure. However, in 1783, several days after Prince Octavius of Great Britain was inoculated, he died. In 1796, the physician Edward Jenner took pus from the hand of a milkmaid with cowpox , scratched it into the arm of an 8-year-old boy, James Phipps , and six weeks later variolated the boy with smallpox, afterwards observing that he did not catch smallpox. Jenner extended his studies and, in 1798, reported that his vaccine was safe in children and adults, and could be transferred from arm-to-arm, which reduced reliance on uncertain supplies from infected cows. In 1804, the Spanish Balmis smallpox vaccination expedition to Spain's colonies Mexico and Philippines used the arm-to-arm transport method to get around the fact the vaccine survived for only 12 days in vitro . They used cowpox. Since vaccination with cowpox was much safer than smallpox inoculation, the latter, though still widely practiced in England, was banned in 1840. Following on from Jenner's work, the second generation of vaccines was introduced in the 1880s by Louis Pasteur who developed vaccines for chicken cholera and anthrax , and from the late nineteenth century vaccines were considered a matter of national prestige. National vaccination policies were adopted and compulsory vaccination laws were passed. In 1931 Alice Miles Woodruff and Ernest Goodpasture documented that the fowlpox virus could be grown in embryonated chicken egg . Soon scientists began cultivating other viruses in eggs. Eggs were used for virus propagation in the development of a yellow fever vaccine in 1935 and an influenza vaccine in 1945. In 1959 growth media and cell culture replaced eggs as the standard method of virus propagation for vaccines. Vaccinology flourished in the twentieth century, which saw the introduction of several successful vaccines, including those against diphtheria , measles , mumps , and rubella . Major achievements included the development of the polio vaccine in the 1950s and the eradication of smallpox during the 1960s and 1970s. Maurice Hilleman was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including herpes simplex , malaria , gonorrhea , and HIV . First generation vaccines are whole-organism vaccines – either live and weakened , or killed forms. Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce killer T-cell (T C or CTL) responses, helper T-cell (T H ) responses and antibody immunity . However, attenuated forms of a pathogen can convert to a dangerous form and may cause disease in immunocompromised vaccine recipients (such as those with AIDS ). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses and may not work at all for some diseases. Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific protein antigens (such as tetanus or diphtheria toxoid ) or recombinant protein components (such as the hepatitis B surface antigen ). They can generate T H and antibody responses, but not killer T cell responses. [ citation needed ] RNA vaccines and DNA vaccines are examples of third generation vaccines. In 2016 a DNA vaccine for the Zika virus began testing at the National Institutes of Health . Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016. Clinical trials for DNA vaccines to prevent HIV are underway. mRNA vaccines such as BNT162b2 were developed in the year 2020 with the help of Operation Warp Speed and massively deployed to combat the COVID-19 pandemic . In 2021, Katalin Karikó and Drew Weissman received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology. First generation vaccines are whole-organism vaccines – either live and weakened , or killed forms. Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce killer T-cell (T C or CTL) responses, helper T-cell (T H ) responses and antibody immunity . However, attenuated forms of a pathogen can convert to a dangerous form and may cause disease in immunocompromised vaccine recipients (such as those with AIDS ). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses and may not work at all for some diseases. Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific protein antigens (such as tetanus or diphtheria toxoid ) or recombinant protein components (such as the hepatitis B surface antigen ). They can generate T H and antibody responses, but not killer T cell responses. [ citation needed ] RNA vaccines and DNA vaccines are examples of third generation vaccines. In 2016 a DNA vaccine for the Zika virus began testing at the National Institutes of Health . Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016. Clinical trials for DNA vaccines to prevent HIV are underway. mRNA vaccines such as BNT162b2 were developed in the year 2020 with the help of Operation Warp Speed and massively deployed to combat the COVID-19 pandemic . In 2021, Katalin Karikó and Drew Weissman received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology. Since at least 2013, scientists have been trying to develop synthetic third-generation vaccines by reconstructing the outside structure of a virus ; it was hoped that this will help prevent vaccine resistance . Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders. For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure . Factors that affect the trends of vaccine development include progress in translatory medicine, demographics , regulatory science , political, cultural, and social responses. The idea of vaccine production via transgenic plants was identified as early as 2003. Plants such as tobacco , potato , tomato , and banana can have genes inserted that cause them to produce vaccines usable for humans. In 2005, bananas were developed that produce a human vaccine against hepatitis B . The idea of vaccine production via transgenic plants was identified as early as 2003. Plants such as tobacco , potato , tomato , and banana can have genes inserted that cause them to produce vaccines usable for humans. In 2005, bananas were developed that produce a human vaccine against hepatitis B . Vaccine hesitancy is a delay in acceptance, or refusal of vaccines despite the availability of vaccine services. The term covers outright refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others. There is an overwhelming scientific consensus that vaccines are generally safe and effective. Vaccine hesitancy often results in disease outbreaks and deaths from vaccine-preventable diseases . The World Health Organization therefore characterized vaccine hesitancy as one of the top ten global health threats in 2019.

Wiki

Chikungunya

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

RNA virus

An RNA virus is a virus — other than a retrovirus — that has ribonucleic acid ( RNA ) as its genetic material . The nucleic acid is usually single-stranded RNA ( ssRNA ) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses include the common cold , influenza , SARS , MERS , COVID-19 , Dengue virus , hepatitis C , hepatitis E , West Nile fever , Ebola virus disease , rabies , polio , mumps , and measles . The International Committee on Taxonomy of Viruses (ICTV) classifies RNA viruses as those that belong to Group III , Group IV or Group V of the Baltimore classification system. This category excludes Group VI , viruses with RNA genetic material but which use DNA intermediates in their life cycle : these are called retroviruses , including HIV-1 and HIV-2 which cause AIDS . As of May 2020, all known RNA viruses encoding an RNA-directed RNA polymerase are believed to form a monophyletic group, known as the realm Riboviria . The majority of such RNA viruses fall into the kingdom Orthornavirae and the rest have a positioning not yet defined . The realm does not contain all RNA viruses: Deltavirus , Asunviroidae , and Pospiviroidae are taxa of RNA viruses that were mistakenly included in 2019, [lower-alpha 1] but corrected in 2020. RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense , or ambisense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. Purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. In contrast, purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. Ambisense RNA viruses resemble negative-sense RNA viruses, except they translate genes from their negative and positive strands. The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi , [lower-alpha 2] and bacteria ), genome segment number (one to twelve), and virion organization ( Triangulation number , capsid layers, spikes, turrets, etc.). Members of this group include the rotaviruses , which are the most common cause of gastroenteritis in young children, and picobirnaviruses , which are the most common virus in fecal samples of both humans and animals with or without signs of diarrhea. Bluetongue virus is an economically important pathogen that infects cattle and sheep. In recent years, progress has been made in determining atomic and subnanometer resolution structures of a number of key viral proteins and virion capsids of several dsRNA viruses, highlighting the significant parallels in the structure and replicative processes of many of these viruses. [ page needed ] RNA viruses generally have very high mutation rates compared to DNA viruses , because viral RNA polymerases lack the proofreading ability of DNA polymerases . The genetic diversity of RNA viruses is one reason why it is difficult to make effective vaccines against them. Retroviruses also have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA before integration. Some genes of RNA virus are important to the viral replication cycles and mutations are not tolerated. For example, the region of the hepatitis C virus genome that encodes the core protein is highly conserved , because it contains an RNA structure involved in an internal ribosome entry site . On average, dsRNA viruses show a lower sequence redundancy relative to ssRNA viruses. Contrarily, dsDNA viruses contain the most redundant genome sequences while ssDNA viruses have the least. The sequence complexity of viruses has been shown to be a key characteristic for accurate reference-free viral classification. RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense , or ambisense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. Purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. In contrast, purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. Ambisense RNA viruses resemble negative-sense RNA viruses, except they translate genes from their negative and positive strands. The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi , [lower-alpha 2] and bacteria ), genome segment number (one to twelve), and virion organization ( Triangulation number , capsid layers, spikes, turrets, etc.). Members of this group include the rotaviruses , which are the most common cause of gastroenteritis in young children, and picobirnaviruses , which are the most common virus in fecal samples of both humans and animals with or without signs of diarrhea. Bluetongue virus is an economically important pathogen that infects cattle and sheep. In recent years, progress has been made in determining atomic and subnanometer resolution structures of a number of key viral proteins and virion capsids of several dsRNA viruses, highlighting the significant parallels in the structure and replicative processes of many of these viruses. [ page needed ]RNA viruses generally have very high mutation rates compared to DNA viruses , because viral RNA polymerases lack the proofreading ability of DNA polymerases . The genetic diversity of RNA viruses is one reason why it is difficult to make effective vaccines against them. Retroviruses also have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA before integration. Some genes of RNA virus are important to the viral replication cycles and mutations are not tolerated. For example, the region of the hepatitis C virus genome that encodes the core protein is highly conserved , because it contains an RNA structure involved in an internal ribosome entry site . On average, dsRNA viruses show a lower sequence redundancy relative to ssRNA viruses. Contrarily, dsDNA viruses contain the most redundant genome sequences while ssDNA viruses have the least. The sequence complexity of viruses has been shown to be a key characteristic for accurate reference-free viral classification. Animal RNA viruses are classified by the ICTV. There are three distinct groups of RNA viruses depending on their genome and mode of replication: Retroviruses (Group VI) have a single-stranded RNA genome but, in general, are not considered RNA viruses because they use DNA intermediates to replicate. Reverse transcriptase , a viral enzyme that comes from the virus itself after it is uncoated, converts the viral RNA into a complementary strand of DNA, which is copied to produce a double-stranded molecule of viral DNA. After this DNA is integrated into the host genome using the viral enzyme integrase , expression of the encoded genes may lead to the formation of new virions.Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are present in the same host cell. Very rarely viral RNA can recombine with host RNA. RNA recombination appears to be a major driving force in determining genome architecture and the course of viral evolution among Picornaviridae ( (+)ssRNA ), e.g. poliovirus . In the Retroviridae ((+)ssRNA), e.g. HIV , damage in the RNA genome appears to be avoided during reverse transcription by strand switching, a form of recombination. Recombination also occurs in the Reoviridae (dsRNA), e.g. reovirus; Orthomyxoviridae ((-)ssRNA), e.g. influenza virus ; and Coronaviridae ((+)ssRNA), e.g. SARS . Recombination in RNA viruses appears to be an adaptation for coping with genome damage. Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. Classification is based principally on the type of genome (double-stranded, negative- or positive-single-strand) and gene number and organization. Currently, there are 5 orders and 47 families of RNA viruses recognized. There are also many unassigned species and genera. Related to but distinct from the RNA viruses are the viroids and the RNA satellite viruses . These are not currently classified as RNA viruses and are described on their own pages. A study of several thousand RNA viruses has shown the presence of at least five main taxa: a levivirus and relatives group; a picornavirus supergroup; an alphavirus supergroup plus a flavivirus supergroup; the dsRNA viruses; and the -ve strand viruses. The lentivirus group appears to be basal to all the remaining RNA viruses. The next major division lies between the picornasupragroup and the remaining viruses. The dsRNA viruses appear to have evolved from a +ve RNA ancestor and the -ve RNA viruses from within the dsRNA viruses. The closest relation to the -ve stranded RNA viruses is the Reoviridae . This is the single largest group of RNA viruses and has been organized by the ICTV into the phyla Kitrinoviricota , Lenarviricota , and Pisuviricota in the kingdom Orthornavirae and realm Riboviria . Positive-strand RNA viruses can also be classified based on the RNA-dependent RNA polymerase. Three groups have been recognised: Bymoviruses, comoviruses, nepoviruses, nodaviruses, picornaviruses, potyviruses, sobemoviruses and a subset of luteoviruses (beet western yellows virus and potato leafroll virus)—the picorna like group (Picornavirata). Carmoviruses, dianthoviruses, flaviviruses, pestiviruses, statoviruses, tombusviruses, single-stranded RNA bacteriophages, hepatitis C virus and a subset of luteoviruses (barley yellow dwarf virus)—the flavi like group (Flavivirata). Alphaviruses, carlaviruses, furoviruses, hordeiviruses, potexviruses, rubiviruses, tobraviruses, tricornaviruses, tymoviruses, apple chlorotic leaf spot virus, beet yellows virus and hepatitis E virus—the alpha like group (Rubivirata). A division of the alpha-like (Sindbis-like) supergroup on the basis of a novel domain located near the N termini of the proteins involved in viral replication has been proposed. The two groups proposed are: the 'altovirus' group (alphaviruses, furoviruses, hepatitis E virus, hordeiviruses, tobamoviruses, tobraviruses, tricornaviruses and probably rubiviruses); and the 'typovirus' group (apple chlorotic leaf spot virus, carlaviruses, potexviruses and tymoviruses). The alpha like supergroup can be further divided into three clades : the rubi-like, tobamo-like, and tymo-like viruses. Additional work has identified five groups of positive-stranded RNA viruses containing four, three, three, three, and one order(s), respectively. These fourteen orders contain 31 virus families (including 17 families of plant viruses) and 48 genera (including 30 genera of plant viruses). This analysis suggests that alphaviruses and flaviviruses can be separated into two families—the Togaviridae and Flaviridae, respectively—but suggests that other taxonomic assignments, such as the pestiviruses, hepatitis C virus, rubiviruses, hepatitis E virus, and arteriviruses, may be incorrect. The coronaviruses and toroviruses appear to be distinct families in distinct orders and not distinct genera of the same family as currently classified. The luteoviruses appear to be two families rather than one, and apple chlorotic leaf spot virus appears not to be a closterovirus but a new genus of the Potexviridae. The evolution of the picornaviruses based on an analysis of their RNA polymerases and helicases appears to date to the divergence of eukaryotes . Their putative ancestors include the bacterial group II retroelements , the family of HtrA proteases and DNA bacteriophages . Partitiviruses are related to and may have evolved from a totivirus ancestor. Hypoviruses and barnaviruses appear to share an ancestry with the potyvirus and sobemovirus lineages respectively. This analysis also suggests that the dsRNA viruses are not closely related to each other but instead belong to four additional classes—Birnaviridae, Cystoviridae, Partitiviridae, and Reoviridae—and one additional order (Totiviridae) of one of the classes of positive ssRNA viruses in the same subphylum as the positive-strand RNA viruses. One study has suggested that there are two large clades: One includes the families Caliciviridae , Flaviviridae , and Picornaviridae and a second that includes the families Alphatetraviridae , Birnaviridae , Cystoviridae , Nodaviridae , and Permutotretraviridae . These viruses have multiple types of genome ranging from a single RNA molecule up to eight segments. Despite their diversity it appears that they may have originated in arthropods and to have diversified from there. A number of satellite viruses—viruses that require the assistance of another virus to complete their life cycle—are also known. Their taxonomy has yet to be settled. The following four genera have been proposed for positive sense single stranded RNA satellite viruses that infect plants— Albetovirus , Aumaivirus , Papanivirus and Virtovirus . A family— Sarthroviridae which includes the genus Macronovirus —has been proposed for the positive sense single stranded RNA satellite viruses that infect arthropods .This is the single largest group of RNA viruses and has been organized by the ICTV into the phyla Kitrinoviricota , Lenarviricota , and Pisuviricota in the kingdom Orthornavirae and realm Riboviria . Positive-strand RNA viruses can also be classified based on the RNA-dependent RNA polymerase. Three groups have been recognised: Bymoviruses, comoviruses, nepoviruses, nodaviruses, picornaviruses, potyviruses, sobemoviruses and a subset of luteoviruses (beet western yellows virus and potato leafroll virus)—the picorna like group (Picornavirata). Carmoviruses, dianthoviruses, flaviviruses, pestiviruses, statoviruses, tombusviruses, single-stranded RNA bacteriophages, hepatitis C virus and a subset of luteoviruses (barley yellow dwarf virus)—the flavi like group (Flavivirata). Alphaviruses, carlaviruses, furoviruses, hordeiviruses, potexviruses, rubiviruses, tobraviruses, tricornaviruses, tymoviruses, apple chlorotic leaf spot virus, beet yellows virus and hepatitis E virus—the alpha like group (Rubivirata). A division of the alpha-like (Sindbis-like) supergroup on the basis of a novel domain located near the N termini of the proteins involved in viral replication has been proposed. The two groups proposed are: the 'altovirus' group (alphaviruses, furoviruses, hepatitis E virus, hordeiviruses, tobamoviruses, tobraviruses, tricornaviruses and probably rubiviruses); and the 'typovirus' group (apple chlorotic leaf spot virus, carlaviruses, potexviruses and tymoviruses). The alpha like supergroup can be further divided into three clades : the rubi-like, tobamo-like, and tymo-like viruses. Additional work has identified five groups of positive-stranded RNA viruses containing four, three, three, three, and one order(s), respectively. These fourteen orders contain 31 virus families (including 17 families of plant viruses) and 48 genera (including 30 genera of plant viruses). This analysis suggests that alphaviruses and flaviviruses can be separated into two families—the Togaviridae and Flaviridae, respectively—but suggests that other taxonomic assignments, such as the pestiviruses, hepatitis C virus, rubiviruses, hepatitis E virus, and arteriviruses, may be incorrect. The coronaviruses and toroviruses appear to be distinct families in distinct orders and not distinct genera of the same family as currently classified. The luteoviruses appear to be two families rather than one, and apple chlorotic leaf spot virus appears not to be a closterovirus but a new genus of the Potexviridae. The evolution of the picornaviruses based on an analysis of their RNA polymerases and helicases appears to date to the divergence of eukaryotes . Their putative ancestors include the bacterial group II retroelements , the family of HtrA proteases and DNA bacteriophages . Partitiviruses are related to and may have evolved from a totivirus ancestor. Hypoviruses and barnaviruses appear to share an ancestry with the potyvirus and sobemovirus lineages respectively. The evolution of the picornaviruses based on an analysis of their RNA polymerases and helicases appears to date to the divergence of eukaryotes . Their putative ancestors include the bacterial group II retroelements , the family of HtrA proteases and DNA bacteriophages . Partitiviruses are related to and may have evolved from a totivirus ancestor. Hypoviruses and barnaviruses appear to share an ancestry with the potyvirus and sobemovirus lineages respectively. This analysis also suggests that the dsRNA viruses are not closely related to each other but instead belong to four additional classes—Birnaviridae, Cystoviridae, Partitiviridae, and Reoviridae—and one additional order (Totiviridae) of one of the classes of positive ssRNA viruses in the same subphylum as the positive-strand RNA viruses. One study has suggested that there are two large clades: One includes the families Caliciviridae , Flaviviridae , and Picornaviridae and a second that includes the families Alphatetraviridae , Birnaviridae , Cystoviridae , Nodaviridae , and Permutotretraviridae . These viruses have multiple types of genome ranging from a single RNA molecule up to eight segments. Despite their diversity it appears that they may have originated in arthropods and to have diversified from there. A number of satellite viruses—viruses that require the assistance of another virus to complete their life cycle—are also known. Their taxonomy has yet to be settled. The following four genera have been proposed for positive sense single stranded RNA satellite viruses that infect plants— Albetovirus , Aumaivirus , Papanivirus and Virtovirus . A family— Sarthroviridae which includes the genus Macronovirus —has been proposed for the positive sense single stranded RNA satellite viruses that infect arthropods .There are twelve families and a number of unassigned genera and species recognised in this group. There are three orders and 34 families recognised in this group. In addition, there are a number of unclassified species and genera. Satellite viruses An unclassified astrovirus/hepevirus-like virus has also been described. With the exception of the Hepatitis D virus , this group of viruses has been placed into a single phylum— Negarnaviricota . This phylum has been divided into two subphyla— Haploviricotina and Polyploviricotina . Within the subphylum Haploviricotina four classes are currently recognised: Chunqiuviricetes , Milneviricetes , Monjiviricetes and Yunchangviricetes . In the subphylum Polyploviricotina two classes are recognised: Ellioviricetes and Insthoviricetes . Six classes, seven orders and twenty four families are currently recognized in this group. A number of unassigned species and genera are yet to be classified.

Wiki

Chikungunya

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

World Health Day

World Health Day is a global health awareness day celebrated every year on 7 April, under the sponsorship of the World Health Organization (WHO), as well as other related organizations. In 1948, the WHO held the First World Health Assembly . The Assembly decided to celebrate 7 April of each year, with effect from 1950, as the World Health Day. The World Health Day is held to mark WHO's founding and is seen as an opportunity by the organization to draw worldwide attention to a subject of major importance to global health each year. The WHO organizes international, regional and local events on the Day related to a particular theme. World Health Day is acknowledged by various governments and non-governmental organizations with interests in public health issues, who also organize activities and highlight their support in media reports, such as the Global Health Council . World Health Day is one of 11 official global health campaigns marked by WHO, along with World Tuberculosis Day , World Immunization Week , World Malaria Day , World No Tobacco Day , World AIDS Day , World Blood Donor Day , World Chagas Disease Day , World Patient Safety Day , World Antimicrobial Awareness Week and World Hepatitis Day . 1991: Should Disaster Strike, be prepared 1992: Heart beat: A rhythm of Health 1993: Handle life with care: Prevent violence and Negligence 1994: Oral Health for a Healthy Life 1995: Global Polio Eradication 1996: Healthy Cities for better life 1997: Emerging infectious diseases 1998: Safe motherhood 1999: Active aging makes the difference 2000: Safe Blood starts with me 2001: Mental Health : stop exclusion, dare to care 2002: Move for health 2003: Shape the future of life: healthy environments for children 2004: Road safety 2005: Make every mother and child count 2006: Working together for health In 2006, World Health Day was devoted to the health workforce crisis, or chronic shortages of health workers around the world due to decades of underinvestment in their education, training, salaries, working environment and management. The day was also meant to celebrate individual health workers – the people who provide health care to those who need it, in other words those at the heart of health systems . The Day also marked the launch of the WHO's World Health Report 2006 , which focused on the same theme. The report contained an assessment of the current crisis in the global health workforce, revealing an estimated shortage of almost 4.3 million physicians, midwives, nurses and other health care providers worldwide, and further proposed a series of actions for countries and the international community to tackle it. In 2008, World Health Day focused on the need to protect health from the adverse effects of climate change and establish links between climate change and health and other development areas such as environment, food, energy, transport. The theme "protecting health from climate change" put health at the centre of the global dialogue about climate change. WHO selected this theme in recognition that climate change is posing ever growing threats to global public health security. World Health Day 2009 focused on the safety of health facilities and the readiness of health workers who treat those affected by emergencies. Health centres and staff are critical lifelines for vulnerable people in disasters – treating injuries , preventing illnesses and caring for people's health needs. Often, already fragile health systems are unable to keep functioning through a disaster, with immediate and future public health consequences. For this year's World Health Day campaign, WHO and international partners underscored the importance of investing in health infrastructure that can withstand hazards and serve people in immediate need, and urged health facilities to implement systems to respond to internal emergencies, such as fires, and ensure the continuity of care. With the campaign "1000 cities, 1000 lives", events were organized worldwide during the week starting 7 April 2010. The global goals of the campaign were: 1000 cities : to open up public spaces to health, whether it be activities in parks, town hall meetings, clean-up campaigns, or closing off portions of streets to motorized vehicles. 1000 lives : to collect 1000 stories of urban health champions who have taken action and had a significant impact on health in their cities. The theme of World Health Day 2011, marked on 7 April 2011, was " antimicrobial resistance and its global spread" and focused on the need for governments and stakeholders to implement the policies and practices needed to prevent and counter the emergence of highly resistant microorganisms . When infections caused by resistant microorganisms fail to respond to standard treatments, including antibiotics and other antimicrobial medicines – also known as drug resistance – this may result in prolonged illness and greater risk of death. On World Health Day 2011, WHO called for intensified global commitment to safeguard antimicrobial medicines for future generations. The organization introduced a six-point policy package to combat the spread of antimicrobial resistance: Commit to a comprehensive, financed national plan with accountability and civil society engagement. Strengthen surveillance and laboratory capacity. Ensure uninterrupted access to essential medicines of assured quality. Regulate and promote rational use of medicines, including in animal husbandry, and ensure proper patient care; reduce use of antimicrobials in food-producing animals. Enhance infection prevention and control. Foster innovations and research and development for new tools. World Health Day 2012 was marked with the slogan "Good health adds life to years". Life expectancy is going up in most countries, meaning more and more people live longer and enter an age when they may need health care . Meanwhile, birth rates are generally falling. Countries and health care systems need to find innovative and sustainable ways to cope with the demographic shift. As stated by John Beard, director of the WHO Department of Ageing and Life Course, "With the rapid ageing of populations, finding the right model for long-term care becomes more and more urgent". Different activities were organized by WHO as well as non-governmental and community organizations around the world to mark World Health Day 2012. The theme of World Health Day 2013, marked on 7 April 2013, was the need to control raised blood pressure (hypertension) as a "silent killer, global public health crisis". The slogan for the campaign was "Healthy Heart Beat, Healthy Blood Pressure". The WHO reports hypertension – which is both preventable and treatable – contributes to the burden of heart disease , stroke and kidney failure, and is an important cause of premature death and disability. The organization estimates one in 3 adults has raised blood pressure. Specific objectives of the World Health Day 2013 campaign were to: raise awareness of the causes and consequences of high blood pressure; provide information on how to prevent high blood pressure and related complications; encourage adults to check their blood pressure and follow the advice of healthcare professionals; encourage self care to prevent high blood pressure; to make blood pressure measurement affordable to all; to incite national and local authorities to create enabling environments for healthy behaviours . World Health Day 2014 put the spotlight on some of the most commonly known vectors – such as mosquitoes, sandflies, bugs, ticks and snails – responsible for transmitting a wide range of parasites and pathogens that can cause many different illnesses. Mosquitoes, for example, transmit malaria – the most deadly vector-borne disease, causing an estimated 660 000 deaths annually worldwide – as well as dengue fever , lymphatic filariasis , chikungunya , Japanese encephalitis , and yellow fever . More than half of the world's population is at risk of these diseases. The goal of the World Health Day 2014 campaign was better protection from vector-borne diseases, especially for families living in areas where diseases are transmitted by vectors, and travelers to countries where they pose a health threat. The campaign advocated for health authorities in countries where vector-borne diseases are a public health problem or emerging threat, to put in place measures to improve surveillance and protection. The WHO promoted improvement of food safety as part of the 2015 World Health Day campaign. Unsafe food — food containing harmful bacteria, viruses, parasites or chemical substances — is responsible for more than 200 diseases, and is linked to the deaths of some 2 million people annually, mostly children. Changes in food production , distribution and consumption ; changes to the environment; new and emerging pathogens; and antimicrobial resistance all pose challenges to food safety systems. The WHO works with countries and partners to strengthen efforts to prevent, detect and respond to foodborne disease outbreaks in line with the Codex Alimentarius , advocating that food safety is a shared responsibility — from farmers and manufacturers to vendors and consumers — and raising awareness about the importance of the part everyone can play in ensuring that the food on our plate is safe to eat. The WHO focused World Health Day 2016, on diabetes – a largely preventable and treatable non-communicable disease that is rapidly increasing in numbers in many countries, most dramatically in low- and middle-income countries . Simple lifestyle measures have been shown to be effective in preventing or delaying the onset of type 2 diabetes, including maintaining normal body weight , engaging in regular physical activity, and eating a healthy diet. Diabetes can be controlled and managed to prevent complications through diagnosis, self-management education, and affordable treatment. The WHO estimates about 422 million people in the world have diabetes, with the disease the direct cause of some 1.5 million deaths. The goals of WHD 2016 are (1) scale up prevention, (2) strengthen care, and (3) enhance surveillance. World Health Day 2017, celebrated on 7 April, aims to mobilize action on depression . This condition affects people of all ages, from all walks of life, in all countries. It impacts on people's ability to carry out everyday tasks, with consequences for families, friends, and even communities, workplaces, and health care systems. At worst, depression can lead to self-inflicted injury and suicide . A better understanding of depression – which can be prevented and treated – will help reduce the stigma associated with the illness, and lead to more people seeking help. World Health Day 2018 theme, "Universal Health Coverage: Everyone, Everywhere", emphasized the idea that health is a fundamental human right, and that all people should be able to have access to health care. The slogan for the day was "Health For All". Several events were held including a panel discussion on universal health coverage which was live streamed . 2018 marked the 70th anniversary of the World Health Organization's founding. The 2019 World Health Day theme was "Universal Health Coverage: Everyone, Everywhere", a repeat of the 2018 theme, with an emphasis on the idea that "Universal Health Coverage is the WHO's number one goal". To commemorate the 2019 World Health Day theme, the World Health Organization launched a campaign to sign a petition for health for all, held a Facebook live event, and shared information about primary health care and universal health coverage "statistics and facts". The 2020 World Health Day theme took place in the context of the COVID-19 global pandemic and was therefore launched as 'Support Nurses and Midwives". Around the world, people spent the day thanking the nurses and health care workers on the frontlines battling the COVID-19 coronavirus. The US White House released a presidential message emphasizing the role public health plays in "building strong, prosperous, and free societies around the world". The celebration of 2020 World Health Day took place around the world in a mostly virtual environment through online press conferences, announcements, and social media due to the worldwide, broad based, "stay at home" order due to the COVID-19 coronavirus pandemic. Much of the efforts were focused on raising funds for the COVID-19 solidarity response fund. In 2006, World Health Day was devoted to the health workforce crisis, or chronic shortages of health workers around the world due to decades of underinvestment in their education, training, salaries, working environment and management. The day was also meant to celebrate individual health workers – the people who provide health care to those who need it, in other words those at the heart of health systems . The Day also marked the launch of the WHO's World Health Report 2006 , which focused on the same theme. The report contained an assessment of the current crisis in the global health workforce, revealing an estimated shortage of almost 4.3 million physicians, midwives, nurses and other health care providers worldwide, and further proposed a series of actions for countries and the international community to tackle it. In 2008, World Health Day focused on the need to protect health from the adverse effects of climate change and establish links between climate change and health and other development areas such as environment, food, energy, transport. The theme "protecting health from climate change" put health at the centre of the global dialogue about climate change. WHO selected this theme in recognition that climate change is posing ever growing threats to global public health security. World Health Day 2009 focused on the safety of health facilities and the readiness of health workers who treat those affected by emergencies. Health centres and staff are critical lifelines for vulnerable people in disasters – treating injuries , preventing illnesses and caring for people's health needs. Often, already fragile health systems are unable to keep functioning through a disaster, with immediate and future public health consequences. For this year's World Health Day campaign, WHO and international partners underscored the importance of investing in health infrastructure that can withstand hazards and serve people in immediate need, and urged health facilities to implement systems to respond to internal emergencies, such as fires, and ensure the continuity of care.With the campaign "1000 cities, 1000 lives", events were organized worldwide during the week starting 7 April 2010. The global goals of the campaign were: 1000 cities : to open up public spaces to health, whether it be activities in parks, town hall meetings, clean-up campaigns, or closing off portions of streets to motorized vehicles. 1000 lives : to collect 1000 stories of urban health champions who have taken action and had a significant impact on health in their cities.The theme of World Health Day 2011, marked on 7 April 2011, was " antimicrobial resistance and its global spread" and focused on the need for governments and stakeholders to implement the policies and practices needed to prevent and counter the emergence of highly resistant microorganisms . When infections caused by resistant microorganisms fail to respond to standard treatments, including antibiotics and other antimicrobial medicines – also known as drug resistance – this may result in prolonged illness and greater risk of death. On World Health Day 2011, WHO called for intensified global commitment to safeguard antimicrobial medicines for future generations. The organization introduced a six-point policy package to combat the spread of antimicrobial resistance: Commit to a comprehensive, financed national plan with accountability and civil society engagement. Strengthen surveillance and laboratory capacity. Ensure uninterrupted access to essential medicines of assured quality. Regulate and promote rational use of medicines, including in animal husbandry, and ensure proper patient care; reduce use of antimicrobials in food-producing animals. Enhance infection prevention and control. Foster innovations and research and development for new tools.World Health Day 2012 was marked with the slogan "Good health adds life to years". Life expectancy is going up in most countries, meaning more and more people live longer and enter an age when they may need health care . Meanwhile, birth rates are generally falling. Countries and health care systems need to find innovative and sustainable ways to cope with the demographic shift. As stated by John Beard, director of the WHO Department of Ageing and Life Course, "With the rapid ageing of populations, finding the right model for long-term care becomes more and more urgent". Different activities were organized by WHO as well as non-governmental and community organizations around the world to mark World Health Day 2012. The theme of World Health Day 2013, marked on 7 April 2013, was the need to control raised blood pressure (hypertension) as a "silent killer, global public health crisis". The slogan for the campaign was "Healthy Heart Beat, Healthy Blood Pressure". The WHO reports hypertension – which is both preventable and treatable – contributes to the burden of heart disease , stroke and kidney failure, and is an important cause of premature death and disability. The organization estimates one in 3 adults has raised blood pressure. Specific objectives of the World Health Day 2013 campaign were to: raise awareness of the causes and consequences of high blood pressure; provide information on how to prevent high blood pressure and related complications; encourage adults to check their blood pressure and follow the advice of healthcare professionals; encourage self care to prevent high blood pressure; to make blood pressure measurement affordable to all; to incite national and local authorities to create enabling environments for healthy behaviours .World Health Day 2014 put the spotlight on some of the most commonly known vectors – such as mosquitoes, sandflies, bugs, ticks and snails – responsible for transmitting a wide range of parasites and pathogens that can cause many different illnesses. Mosquitoes, for example, transmit malaria – the most deadly vector-borne disease, causing an estimated 660 000 deaths annually worldwide – as well as dengue fever , lymphatic filariasis , chikungunya , Japanese encephalitis , and yellow fever . More than half of the world's population is at risk of these diseases. The goal of the World Health Day 2014 campaign was better protection from vector-borne diseases, especially for families living in areas where diseases are transmitted by vectors, and travelers to countries where they pose a health threat. The campaign advocated for health authorities in countries where vector-borne diseases are a public health problem or emerging threat, to put in place measures to improve surveillance and protection.The WHO promoted improvement of food safety as part of the 2015 World Health Day campaign. Unsafe food — food containing harmful bacteria, viruses, parasites or chemical substances — is responsible for more than 200 diseases, and is linked to the deaths of some 2 million people annually, mostly children. Changes in food production , distribution and consumption ; changes to the environment; new and emerging pathogens; and antimicrobial resistance all pose challenges to food safety systems. The WHO works with countries and partners to strengthen efforts to prevent, detect and respond to foodborne disease outbreaks in line with the Codex Alimentarius , advocating that food safety is a shared responsibility — from farmers and manufacturers to vendors and consumers — and raising awareness about the importance of the part everyone can play in ensuring that the food on our plate is safe to eat. The WHO focused World Health Day 2016, on diabetes – a largely preventable and treatable non-communicable disease that is rapidly increasing in numbers in many countries, most dramatically in low- and middle-income countries . Simple lifestyle measures have been shown to be effective in preventing or delaying the onset of type 2 diabetes, including maintaining normal body weight , engaging in regular physical activity, and eating a healthy diet. Diabetes can be controlled and managed to prevent complications through diagnosis, self-management education, and affordable treatment. The WHO estimates about 422 million people in the world have diabetes, with the disease the direct cause of some 1.5 million deaths. The goals of WHD 2016 are (1) scale up prevention, (2) strengthen care, and (3) enhance surveillance. World Health Day 2017, celebrated on 7 April, aims to mobilize action on depression . This condition affects people of all ages, from all walks of life, in all countries. It impacts on people's ability to carry out everyday tasks, with consequences for families, friends, and even communities, workplaces, and health care systems. At worst, depression can lead to self-inflicted injury and suicide . A better understanding of depression – which can be prevented and treated – will help reduce the stigma associated with the illness, and lead to more people seeking help. World Health Day 2018 theme, "Universal Health Coverage: Everyone, Everywhere", emphasized the idea that health is a fundamental human right, and that all people should be able to have access to health care. The slogan for the day was "Health For All". Several events were held including a panel discussion on universal health coverage which was live streamed . 2018 marked the 70th anniversary of the World Health Organization's founding. The 2019 World Health Day theme was "Universal Health Coverage: Everyone, Everywhere", a repeat of the 2018 theme, with an emphasis on the idea that "Universal Health Coverage is the WHO's number one goal". To commemorate the 2019 World Health Day theme, the World Health Organization launched a campaign to sign a petition for health for all, held a Facebook live event, and shared information about primary health care and universal health coverage "statistics and facts". The 2020 World Health Day theme took place in the context of the COVID-19 global pandemic and was therefore launched as 'Support Nurses and Midwives". Around the world, people spent the day thanking the nurses and health care workers on the frontlines battling the COVID-19 coronavirus. The US White House released a presidential message emphasizing the role public health plays in "building strong, prosperous, and free societies around the world". The celebration of 2020 World Health Day took place around the world in a mostly virtual environment through online press conferences, announcements, and social media due to the worldwide, broad based, "stay at home" order due to the COVID-19 coronavirus pandemic. Much of the efforts were focused on raising funds for the COVID-19 solidarity response fund.

Wiki

Chikungunya

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

Varicella vaccine

none Varicella vaccine , also known as chickenpox vaccine , is a vaccine that protects against chickenpox . One dose of vaccine prevents 95% of moderate disease and 100% of severe disease. Two doses of vaccine are more effective than one. If given to those who are not immune within five days of exposure to chickenpox it prevents most cases of disease. Vaccinating a large portion of the population also protects those who are not vaccinated. It is given by injection just under the skin . Another vaccine, known as zoster vaccine , is used to prevent diseases caused by the same virus – the varicella zoster virus . The World Health Organization (WHO) recommends routine vaccination only if a country can keep more than 80% of people vaccinated. If only 20% to 80% of people are vaccinated it is possible that more people will get the disease at an older age and outcomes overall may worsen. Either one or two doses of the vaccine is recommended. In the United States two doses are recommended starting at twelve to fifteen months of age. As of 2017 [ update ] , twenty-three countries recommend all non-medically exempt children receive the vaccine, nine recommend it only for high risk groups, three additional countries recommend use in only parts of the country, while other countries make no recommendation. Not all countries provide the vaccine due to its cost. In the United Kingdom , Varilrix, a live viral vaccine is approved from the age of 12 months, but only recommended for certain at risk groups. Minor side effects may include pain at the site of injection, fever, and rash. Severe side effects are rare and occur mostly in those with poor immune function . Its use in people with HIV/AIDS should be done with care. It is not recommended during pregnancy ; however, the few times it has been given during pregnancy no problems resulted. The vaccine is available either by itself or along with the MMR vaccine , in a version known as the MMRV vaccine . It is made from weakened virus . A live attenuated varicella vaccine, the Oka strain, was developed by Michiaki Takahashi and his colleagues in Japan in the early 1970s. American vaccinologist Maurice Hilleman 's team developed a chickenpox vaccine in the United States in 1981, based on the "Oka strain" of the varicella virus. The chickenpox vaccine first became commercially available in 1984. It is on the WHO Model List of Essential Medicines . Varicella vaccine is 70% to 90% effective for preventing varicella and more than 95% effective for preventing severe varicella. Follow-up evaluations have taken place in the United States of children immunized that revealed protection for at least 11 years. Studies were conducted in Japan which indicated protection for at least 20 years. People who do not develop enough protection when they get the vaccine may develop a mild case of the disease when in close contact with a person with chickenpox. In these cases, people show very little sign of illness. This has been the case of children who get the vaccine in their early childhood and later have contact with children with chickenpox. Some of these children may develop a mild chickenpox also known as breakthrough disease. Another vaccine, known as zoster vaccine , is simply a larger-than-normal dose of the same vaccine used against chickenpox, and is used in older adults to reduce the risk of shingles (also called herpes zoster) and postherpetic neuralgia , which are caused by the same virus. The recombinant zoster (shingles) vaccine is recommended for adults aged 50 years and older. The long-term duration of protection from varicella vaccine is unknown, but there are now persons vaccinated twenty years ago with no evidence of waning immunity, while others have become vulnerable in as few as six years. Assessments of duration of immunity are complicated in an environment where natural disease is still common, which typically leads to an overestimation of effectiveness. Some vaccinated children have been found to lose their protective antibody in as little as five to eight years. However, according to the World Health Organization (WHO): "After observation of study populations for periods of up to 20 years in Japan and 10 years in the United States, more than 90% of immunocompetent persons who were vaccinated as children were still protected from varicella." However, since only one out of five Japanese children were vaccinated, the annual exposure of these vaccinees to children with natural chickenpox boosted the vaccinees' immune system. In the United States, where universal varicella vaccination has been practiced, the majority of children no longer receive exogenous (outside) boosting, thus, their cell-mediated immunity to VZV ( varicella zoster virus ) wanes – necessitating booster chickenpox vaccinations. As time goes on, boosters may be necessary. Persons exposed to the virus after vaccination tend to experience milder cases of chickenpox if they develop the disease. Catching "wild" chickenpox as a child has been thought to commonly result in lifelong immunity. Indeed, parents have deliberately ensured this in the past with " pox parties ". Historically, exposure of adults to contagious children has boosted their immunity, reducing the risk of shingles. [ better source needed ] The US Centers for Disease Control and Prevention (CDC) and corresponding national organizations are carefully observing the failure rate which may be high compared with other modern vaccines – large outbreaks of chickenpox having occurred at schools which required their children to be vaccinated. Prior to the widespread introduction of the vaccine in the United States in 1995 (1986 in Japan and 1988 in Korea ), there were around 4,000,000 cases per year in the United States, mostly in children, with typically 10,500–13,000 hospital admissions (range, 8,000–18,000), and 100–150 deaths each year. Most of the deaths were among young children. During 2003, and the first half of 2004, the CDC reported eight deaths from varicella, six of whom were children or adolescents. These deaths and hospital admissions have substantially declined in the US due to vaccination, though the rate of shingles infection has increased as adults are less exposed to infected children (which would otherwise help protect against shingles). Ten years after the vaccine was recommended in the US, the CDC reported as much as a 90% drop in chickenpox cases, a varicella-related hospital admission decline of 71% and a 97% drop in chickenpox deaths among those under 20. Vaccines are less effective among high-risk patients, as well as being more dangerous because they contain attenuated live virus. In a study performed on children with an impaired immune system , 30% had lost the antibody after five years, and 8% had already caught wild chickenpox in that five-year period. Herpes zoster (shingles) most often occurs in the elderly and is only rarely seen in children. The incidence of herpes zoster in vaccinated adults is 0.9/1000 person-years, and is 0.33/1000 person-years in vaccinated children; this is lower than the overall incidence of 3.2–4.2/1000 person-years. The risk of developing shingles is reduced for children who receive the varicella vaccine, but not eliminated. The CDC stated in 2014: "Chickenpox vaccines contain weakened live VZV, which may cause latent (dormant) infection. The vaccine-strain VZV can reactivate later in life and cause shingles. However, the risk of getting shingles from vaccine-strain VZV after chickenpox vaccination is much lower than getting shingles after natural infection with wild-type VZV." The risk of shingles is significantly lower among children who have received varicella vaccination, including those who are immunocompromised. The risk of shingles is approximately 80% lower among healthy vaccinated children compared to unvaccinated children who had wild-type varicella. A population with high varicella vaccination also has lower incidence of shingles in unvaccinated children, due to herd immunity . The WHO recommends one or two doses with the initial dose given at 12 to 18 months of age. The second dose, if given, should occur at least one to three months later. The second dose, if given, provides the additional benefit of improved protection against all varicella. This vaccine is a shot given subcutaneously (under the skin). It is recommended for all children under 13 and for everyone 13 or older who has never had chickenpox. In the United States, two doses are recommended by the CDC. For a routine vaccination, the first dose is administered at 12 to 15 months of age and a second dose at age 4–6 years. However, the second dose can be given as early as 3 months after the first dose. If an individual misses the timing for the routine vaccination, the individual is eligible to receive a catch-up vaccination. For a catch-up vaccination, individuals between 7 and 12 years old should receive a two-dose series 3 months apart (a minimum interval of 4 weeks). For individuals 13–18 years old, the catch-up vaccination should be given 4 to 8 weeks apart (a minimum interval of 4 weeks). The varicella vaccine did not become widely available in the United States until 1995. In the UK, the vaccine is only available on the National Health Service for those who are in close contact with someone who is particularly vulnerable to chickenpox. As there is an increased risk of shingles in adults due to possible lack of contact with chickenpox-infected children providing a natural boosting to immunity, and the fact that chickenpox is usually a mild illness, the NHS cites concerns about unvaccinated children catching chickenpox as adults when it is more dangerous. However, the vaccine is approved for 12 months and up and is available privately, with a second dose to be given a year after the first. The long-term duration of protection from varicella vaccine is unknown, but there are now persons vaccinated twenty years ago with no evidence of waning immunity, while others have become vulnerable in as few as six years. Assessments of duration of immunity are complicated in an environment where natural disease is still common, which typically leads to an overestimation of effectiveness. Some vaccinated children have been found to lose their protective antibody in as little as five to eight years. However, according to the World Health Organization (WHO): "After observation of study populations for periods of up to 20 years in Japan and 10 years in the United States, more than 90% of immunocompetent persons who were vaccinated as children were still protected from varicella." However, since only one out of five Japanese children were vaccinated, the annual exposure of these vaccinees to children with natural chickenpox boosted the vaccinees' immune system. In the United States, where universal varicella vaccination has been practiced, the majority of children no longer receive exogenous (outside) boosting, thus, their cell-mediated immunity to VZV ( varicella zoster virus ) wanes – necessitating booster chickenpox vaccinations. As time goes on, boosters may be necessary. Persons exposed to the virus after vaccination tend to experience milder cases of chickenpox if they develop the disease. Catching "wild" chickenpox as a child has been thought to commonly result in lifelong immunity. Indeed, parents have deliberately ensured this in the past with " pox parties ". Historically, exposure of adults to contagious children has boosted their immunity, reducing the risk of shingles. [ better source needed ] The US Centers for Disease Control and Prevention (CDC) and corresponding national organizations are carefully observing the failure rate which may be high compared with other modern vaccines – large outbreaks of chickenpox having occurred at schools which required their children to be vaccinated. Prior to the widespread introduction of the vaccine in the United States in 1995 (1986 in Japan and 1988 in Korea ), there were around 4,000,000 cases per year in the United States, mostly in children, with typically 10,500–13,000 hospital admissions (range, 8,000–18,000), and 100–150 deaths each year. Most of the deaths were among young children. During 2003, and the first half of 2004, the CDC reported eight deaths from varicella, six of whom were children or adolescents. These deaths and hospital admissions have substantially declined in the US due to vaccination, though the rate of shingles infection has increased as adults are less exposed to infected children (which would otherwise help protect against shingles). Ten years after the vaccine was recommended in the US, the CDC reported as much as a 90% drop in chickenpox cases, a varicella-related hospital admission decline of 71% and a 97% drop in chickenpox deaths among those under 20. Vaccines are less effective among high-risk patients, as well as being more dangerous because they contain attenuated live virus. In a study performed on children with an impaired immune system , 30% had lost the antibody after five years, and 8% had already caught wild chickenpox in that five-year period. Herpes zoster (shingles) most often occurs in the elderly and is only rarely seen in children. The incidence of herpes zoster in vaccinated adults is 0.9/1000 person-years, and is 0.33/1000 person-years in vaccinated children; this is lower than the overall incidence of 3.2–4.2/1000 person-years. The risk of developing shingles is reduced for children who receive the varicella vaccine, but not eliminated. The CDC stated in 2014: "Chickenpox vaccines contain weakened live VZV, which may cause latent (dormant) infection. The vaccine-strain VZV can reactivate later in life and cause shingles. However, the risk of getting shingles from vaccine-strain VZV after chickenpox vaccination is much lower than getting shingles after natural infection with wild-type VZV." The risk of shingles is significantly lower among children who have received varicella vaccination, including those who are immunocompromised. The risk of shingles is approximately 80% lower among healthy vaccinated children compared to unvaccinated children who had wild-type varicella. A population with high varicella vaccination also has lower incidence of shingles in unvaccinated children, due to herd immunity . The WHO recommends one or two doses with the initial dose given at 12 to 18 months of age. The second dose, if given, should occur at least one to three months later. The second dose, if given, provides the additional benefit of improved protection against all varicella. This vaccine is a shot given subcutaneously (under the skin). It is recommended for all children under 13 and for everyone 13 or older who has never had chickenpox. In the United States, two doses are recommended by the CDC. For a routine vaccination, the first dose is administered at 12 to 15 months of age and a second dose at age 4–6 years. However, the second dose can be given as early as 3 months after the first dose. If an individual misses the timing for the routine vaccination, the individual is eligible to receive a catch-up vaccination. For a catch-up vaccination, individuals between 7 and 12 years old should receive a two-dose series 3 months apart (a minimum interval of 4 weeks). For individuals 13–18 years old, the catch-up vaccination should be given 4 to 8 weeks apart (a minimum interval of 4 weeks). The varicella vaccine did not become widely available in the United States until 1995. In the UK, the vaccine is only available on the National Health Service for those who are in close contact with someone who is particularly vulnerable to chickenpox. As there is an increased risk of shingles in adults due to possible lack of contact with chickenpox-infected children providing a natural boosting to immunity, and the fact that chickenpox is usually a mild illness, the NHS cites concerns about unvaccinated children catching chickenpox as adults when it is more dangerous. However, the vaccine is approved for 12 months and up and is available privately, with a second dose to be given a year after the first. The varicella vaccine is not recommended for seriously ill people, pregnant women, people who have tuberculosis, people who have experienced a serious allergic reaction to the varicella vaccine in the past, people who are allergic to gelatin , people allergic to neomycin , people receiving high doses of steroids , people receiving treatment for cancer with x-rays or chemotherapy , as well as people who have received blood products or transfusions during the past five months. Additionally, the varicella vaccine is not recommended for people who are taking salicylates (e.g. aspirin). After receiving the varicella vaccine, the use of salicylates should be avoided for at least six weeks. The varicella vaccine is also not recommended for individuals who have received a live vaccine in the last four weeks, because live vaccines that are administered too soon within one another may not be as effective. It may be usable in people with HIV infections who have a good blood count and are receiving appropriate treatment. Specific antiviral medication, such as acyclovir, famciclovir, or valacyclovir, are not recommended 24 hours before and 14 days after vaccination. Serious side effects are very rare. From 1998 to 2013, only one vaccine-related death was reported: an English child with pre-existent leukemia. On some occasions, severe reactions such as meningitis and pneumonia have been reported (mainly in inadvertently vaccinated immunocompromised children) as well as anaphylaxis . The possible mild side effects include redness, stiffness , and soreness at the injection site, as well as fever . A few people may develop a mild rash , which usually appears around the injection site. There is a short-term risk of developing herpes zoster (shingles) following vaccination. However, this risk is less than the risk due to a natural infection resulting in chickenpox. : 378 Most of the cases reported have been mild and have not been associated with serious complications. Approximately 5% of children who receive the vaccine develop a fever or rash. Adverse reaction reports for the period 1995 to 2005 found no deaths attributed to the vaccine despite approximately 55.7 million doses being delivered. Cases of vaccine-related chickenpox have been reported in patients with a weakened immune system, but no deaths. The literature contains several reports of adverse reactions following varicella vaccination, including vaccine-strain zoster in children and adults. The varicella zoster vaccine is made from the Oka/ Merck strain of live attenuated varicella virus. The Oka virus was initially obtained from a child with natural varicella, introduced into human embryonic lung cell cultures, adapted to and propagated in embryonic guinea pig cell cultures, and finally propagated in a human diploid cell line originally derived from fetal tissues ( WI-38 ). Takahashi and his colleagues used the Oka strain to develop a live attenuated varicella vaccine in Japan in the early 1970s. This strain was further developed by pharmaceutical companies such as Merck & Co. and GlaxoSmithKline . American vaccinologist Maurice Hilleman 's team at Merck then used the Oka strain to prepare a chickenpox vaccine in 1981. Japan was among the first countries to vaccinate for chickenpox. The vaccine developed by Hilleman was first licensed in the United States in 1995. Routine vaccination against varicella zoster virus is also performed in the United States, and the incidence of chickenpox has been dramatically reduced there (from four million cases per year in the pre-vaccine era to approximately 390,000 cases per year as of 2014 [ update ] ). As of 2019 [ update ] , standalone varicella vaccines are available in all 27 European Union member countries, and 16 countries also offer a combined measles, mumps, rubella and varicella vaccine (MMRV). Twelve European countries (Austria, Andorra, Cyprus, Czech Republic, Finland, Germany, Greece, Hungary, Italy, Latvia, Luxembourg and Spain) have universal varicella vaccination (UVV) policies, though only six of these countries have made it available at no cost via government funding. EU member states that have not implemented UVV cite reasons such as "a perceived low disease burden and low public health priority," the cost and cost-effectiveness , the possible risk of herpes zoster when vaccinating older adults, and rare fevers leading to seizures after the first dose of the MMRV vaccine. "Countries that implemented UVV experienced decreases in varicella incidence, hospitalizations and complications, showing overall beneficial impact." Varicella vaccination is recommended in Canada for all healthy children aged 1 to 12, as well as susceptible adolescents and adults 50 years of age and younger; "may be considered for people with select immunodeficiency disorders; and "should be prioritized" for susceptible individuals, including "non-pregnant women of childbearing age, household contacts of immunocompromised individuals, members of a household expecting a newborn, health care workers , adults who may be exposed occupationally to varicella (for example, people who work with young children), immigrants and refugees from tropical regions, people receiving chronic salicylate therapy (for example, acetylsalicylic acid [ASA])," and others. Australia has adopted recommendations for routine immunization of children and susceptible adults against chickenpox. Other countries, such as the United Kingdom, have targeted recommendations for the vaccine, e.g., for susceptible health care workers at risk of varicella exposure. In the UK, varicella antibodies are measured as part of the routine of prenatal care , and by 2005 all National Health Service personnel had determined their immunity and been immunized if they were non-immune and have direct patient contact. Population-based immunization against varicella is not otherwise practised in the UK. Since 2013, the MMRV vaccine is offered for free to all Brazilian citizens. The Roman Catholic Church is opposed to abortion. Nevertheless, the Pontifical Academy for Life stated in 2017 that "clinically recommended vaccinations can be used with a clear conscience and that the use of such vaccines does not signify some sort of cooperation with voluntary abortion". On 21 December 2020, the Vatican's doctrinal office, the Congregation for the Doctrine of the Faith , further clarified that it is "morally licit " for Catholics to receive vaccines derived from fetal cell lines or in which such lines were used in testing or development, because "passive material cooperation in the procured abortion from which these cell lines originate is, on the part of those making use of the resulting vaccines, remote" and "does not and should not in any way imply that there is a moral endorsement of the use of cell lines proceeding from aborted fetuses". The Roman Catholic Church is opposed to abortion. Nevertheless, the Pontifical Academy for Life stated in 2017 that "clinically recommended vaccinations can be used with a clear conscience and that the use of such vaccines does not signify some sort of cooperation with voluntary abortion". On 21 December 2020, the Vatican's doctrinal office, the Congregation for the Doctrine of the Faith , further clarified that it is "morally licit " for Catholics to receive vaccines derived from fetal cell lines or in which such lines were used in testing or development, because "passive material cooperation in the procured abortion from which these cell lines originate is, on the part of those making use of the resulting vaccines, remote" and "does not and should not in any way imply that there is a moral endorsement of the use of cell lines proceeding from aborted fetuses".

Wiki

Chikungunya

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

Varicella zoster virus

Varicella zoster virus ( VZV ), also known as human herpesvirus 3 ( HHV-3 , HHV3 ) or Human alphaherpesvirus 3 ( taxonomically ), is one of nine known herpes viruses that can infect humans . It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zoster) in adults but rarely in children. VZV infections are species -specific to humans. The virus can survive in external environments for a few hours. VZV multiplies in the tonsils, and causes a wide variety of symptoms. Similar to the herpes simplex viruses , after primary infection with VZV (chickenpox), the virus lies dormant in neurons, including the cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia. Many years after the person has recovered from initial chickenpox infection, VZV can reactivate to cause shingles . Primary varicella zoster virus infection results in chickenpox (varicella), which may result in complications including encephalitis , pneumonia (either direct viral pneumonia or secondary bacterial pneumonia ), or bronchitis (either viral bronchitis or secondary bacterial bronchitis). Even when clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person ( virus latency ), in the trigeminal and dorsal root ganglia . VZV enters through the respiratory system and has an incubation period of 10–21 days, with an average of 14 days. Targeting the skin and peripheral nerves , the period of illness lasts about 3 to 4 days. Infected individuals are most contagious 1–2 days before the lesions appear. Signs and symptoms include vesicles that fill with pus, rupture, and scab before healing. Lesions most commonly occur on the face, throat, the lower back, the chest and shoulders. In about a third of cases, VZV reactivates in later life, producing a disease known as shingles or herpes zoster. The individual lifetime risk of developing herpes zoster is thought to be between 20% and 30%, or approximately 1 in 4 people. However, for people aged 85 and over, this risk increases to 1 in 2. In a study in Sweden by Nilsson et al. (2015) the annual incidence of herpes zoster infection is estimated at a total of 315 cases per 100,000 inhabitants for all ages and 577 cases per 100,000 for people 50 years of age or older. VZV can also infect the central nervous system, with a 2013 article reporting an incidence rate of 1.02 cases per 100,000 inhabitants in Switzerland, and an annual incidence rate of 1.8 cases per 100,000 inhabitants in Sweden. Shingles lesions and the associated pain, often described as burning, tend to occur on the skin that is innervated by one or two adjacent sensory nerves, almost always on one side of the body only. The skin lesions usually subside over the course of several weeks, while the pain often persists longer. In 10–15% of cases the pain persists more than three months, a chronic and often disabling condition known as postherpetic neuralgia . Other serious complications of varicella zoster infection include Mollaret's meningitis , zoster multiplex, and inflammation of arteries in the brain leading to stroke, myelitis, herpes ophthalmicus, or zoster sine herpete. In Ramsay Hunt syndrome , VZV affects the geniculate ganglion giving lesions that follow specific branches of the facial nerve. Symptoms may include painful blisters on the tongue and ear along with one-sided facial weakness and hearing loss. After infection during initial stages of pregnancy, the fetus can be severely damaged. Reye's syndrome can happen after initial infection, causing continuous vomiting and signs of brain dysfunction such as extreme drowsiness or combative behavior. In some cases, death or coma can follow. Reye's syndrome mostly affects children and teenagers; using aspirin during infection can increase this risk. Primary varicella zoster virus infection results in chickenpox (varicella), which may result in complications including encephalitis , pneumonia (either direct viral pneumonia or secondary bacterial pneumonia ), or bronchitis (either viral bronchitis or secondary bacterial bronchitis). Even when clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person ( virus latency ), in the trigeminal and dorsal root ganglia . VZV enters through the respiratory system and has an incubation period of 10–21 days, with an average of 14 days. Targeting the skin and peripheral nerves , the period of illness lasts about 3 to 4 days. Infected individuals are most contagious 1–2 days before the lesions appear. Signs and symptoms include vesicles that fill with pus, rupture, and scab before healing. Lesions most commonly occur on the face, throat, the lower back, the chest and shoulders. In about a third of cases, VZV reactivates in later life, producing a disease known as shingles or herpes zoster. The individual lifetime risk of developing herpes zoster is thought to be between 20% and 30%, or approximately 1 in 4 people. However, for people aged 85 and over, this risk increases to 1 in 2. In a study in Sweden by Nilsson et al. (2015) the annual incidence of herpes zoster infection is estimated at a total of 315 cases per 100,000 inhabitants for all ages and 577 cases per 100,000 for people 50 years of age or older. VZV can also infect the central nervous system, with a 2013 article reporting an incidence rate of 1.02 cases per 100,000 inhabitants in Switzerland, and an annual incidence rate of 1.8 cases per 100,000 inhabitants in Sweden. Shingles lesions and the associated pain, often described as burning, tend to occur on the skin that is innervated by one or two adjacent sensory nerves, almost always on one side of the body only. The skin lesions usually subside over the course of several weeks, while the pain often persists longer. In 10–15% of cases the pain persists more than three months, a chronic and often disabling condition known as postherpetic neuralgia . Other serious complications of varicella zoster infection include Mollaret's meningitis , zoster multiplex, and inflammation of arteries in the brain leading to stroke, myelitis, herpes ophthalmicus, or zoster sine herpete. In Ramsay Hunt syndrome , VZV affects the geniculate ganglion giving lesions that follow specific branches of the facial nerve. Symptoms may include painful blisters on the tongue and ear along with one-sided facial weakness and hearing loss. After infection during initial stages of pregnancy, the fetus can be severely damaged. Reye's syndrome can happen after initial infection, causing continuous vomiting and signs of brain dysfunction such as extreme drowsiness or combative behavior. In some cases, death or coma can follow. Reye's syndrome mostly affects children and teenagers; using aspirin during infection can increase this risk. VZV is closely related to the herpes simplex viruses (HSV), sharing much genome homology. The known envelope glycoproteins (gB, gC, gE, gH, gI, gK, gL) correspond with those in HSV; however, there is no equivalent of the HSV gD protein. VZV also fails to produce the LAT (latency-associated transcripts) that play an important role in establishing HSV latency (herpes simplex virus). VZV virions are spherical and 180–200 nm in diameter. Their lipid envelope encloses the 100 nm nucleocapsid of 162 hexameric and pentameric capsomeres arranged in an icosahedral form. Its DNA is a single, linear, double-stranded molecule, 125,000 nt long. The capsid is surrounded by loosely associated proteins known collectively as the tegument; many of these proteins play critical roles in initiating the process of virus reproduction in the infected cell. The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion, each approximately 8 nm long. The genome was first sequenced in 1986. It is a linear duplex DNA molecule, a laboratory strain has 124,884 base pairs . The genome has two predominant isomers , depending on the orientation of the S segment, P (prototype) and I S (inverted S) which are present with equal frequency for a total frequency of 90–95%. The L segment can also be inverted resulting in a total of four linear isomers (I L and I LS ). This is distinct from HSV's equiprobable distribution, and the discriminatory mechanism is not known. A small percentage of isolated molecules are circular genomes , about which little is known. (It is known that HSV circularizes on infection.) There are at least 70 open reading frames in the genome.Commonality with HSV1 and HSV2 indicates a common ancestor; five genes (out of about 70) do not have corresponding HSV genes. Relation with other human herpes viruses is less strong, but many homologues and conserved gene blocks are still found. There are at least five clades of this virus. Clades 1 and 3 include European/North American strains; clade 2 are Asian strains, especially from Japan; and clade 5 appears to be based in India . Clade 4 includes some strains from Europe but its geographic origins need further clarification. There are also four genotypes that do not fit into these clades. Allocation of VZV strains to clades required sequence of whole virus genome. Practically all molecular epidemiological data on global VZV strains distribution are obtained with targeted sequencing of selected regions. Phylogenetic analysis of VZV genomic sequences resolves wild-type strains into nine genotypes (E1, E2, J, M1, M2, M3, M4, VIII and IX). Complete sequences for M3 and M4 strains are unavailable, but targeted analyses of representative strains suggest they are stable, circulating VZV genotypes. Sequence analysis of VZV isolates identified both shared and specific markers for every genotype and validated a unified VZV genotyping strategy. Despite high genotype diversity no evidence for intra-genotypic recombination was observed. Five of seven VZV genotypes were reliably discriminated using only four single nucleotide polymorphisms (SNP) present in ORF22, and the E1 and E2 genotypes were resolved using SNP located in ORF21, ORF22 or ORF50. Sequence analysis of 342 clinical varicella and zoster specimens from 18 European countries identified the following distribution of VZV genotypes: E1, 221 (65%); E2, 87 (25%); M1, 20 (6%); M2, 3 (1%); M4, 11 (3%). No M3 or J strains were observed. Of 165 clinical varicella and zoster isolates from Australia and New Zealand typed using this approach, 67 of 127 eastern Australian isolates were E1, 30 were E2, 16 were J, 10 were M1, and 4 were M2; 25 of 38 New Zealand isolates were E1, 8 were E2, and 5 were M1. The mutation rate for synonymous and nonsynonymous mutation rates among the herpesviruses have been estimated at 1 × 10 −7 and 2.7 × 10 −8 mutations/site/year, respectively, based on the highly conserved gB gene. Within the human body it can be treated by a number of drugs and therapeutic agents including acyclovir for chickenpox, famciclovir , valaciclovir for the shingles, zoster-immune globulin (ZIG), and vidarabine . Acyclovir is frequently used as the drug of choice in primary VZV infections, and beginning its administration early can significantly shorten the duration of any symptoms. However, reaching an effective serum concentration of acyclovir typically requires intravenous administration, making its use more difficult outside of a hospital. A live attenuated VZV Oka/Merck strain vaccine is available and is marketed in the United States under the trade name Varivax . It was developed by Merck, Sharp & Dohme in the 1980s from the Oka strain virus isolated and attenuated by Michiaki Takahashi and colleagues in the 1970s. It was submitted to the US Food and Drug Administration (FDA) for approval in 1990 and was approved in 1995. Since then, it has been added to the recommended vaccination schedules for children in Australia , the United States, and many other countries. Varicella vaccination has raised concerns in some that the immunity induced by the vaccine may not be lifelong, possibly leaving adults vulnerable to more severe disease as the immunity from their childhood immunization wanes. Vaccine coverage in the United States in the population recommended for vaccination is approaching 90%, with concomitant reductions in the incidence of varicella cases and hospitalizations and deaths due to VZV. [ citation needed ] So far, clinical data has proved that the vaccine is effective for over ten years in preventing varicella infection in healthy individuals, and when breakthrough infections do occur, illness is typically mild. In 2006, the CDC's Advisory Committee on Immunization Practices (ACIP) recommended a second dose of vaccine before school entry to ensure the maintenance of high levels of varicella immunity. In 2006, the FDA approved Zostavax for the prevention of shingles. Zostavax is a more concentrated formulation of the Varivax vaccine, designed to elicit an immune response in older adults whose immunity to VZV wanes with advancing age. A systematic review by Cochrane (updated in 2023) shows that Zostavax reduces the incidence of shingles by almost 50%. Shingrix is a subunit vaccine (HHV3 glycoprotein E) developed by GlaxoSmithKline which was approved in the United States by the FDA in October 2017. The ACIP recommended Shingrix for adults over the age of 50, including those who have already received Zostavax. The committee voted that Shingrix is preferred over Zostavax for the prevention of zoster and related complications because phase 3 clinical data showed vaccine efficacy of >90% against shingles across all age groups, as well as sustained efficacy over a four-year follow-up. Unlike Zostavax, which is given as a single shot, Shingrix is given as two intramuscular doses, two to six months apart. This vaccine has shown to be immunogenic and safe in adults with human immunodeficiency virus. Chickenpox-like rashes were recognized and described by ancient civilizations; the relationship between zoster and chickenpox was not realized until 1888. In 1943, the similarity between virus particles isolated from the lesions of zoster and those from chickenpox was noted. In 1974 the first chickenpox vaccine was introduced. The varicella zoster virus was first isolated by Evelyn Nicol while she was working at Cleveland City Hospital. Thomas Huckle Weller also isolated the virus and found evidence that the same virus was responsible for both chickenpox and herpes zoster. The etymology of the name of the virus comes from the two diseases it causes, varicella and herpes zoster. The word varicella is possibly derived from variola , a term for smallpox coined by Rudolph Augustin Vogel in 1764.

Wiki

Chikungunya

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

Epidemiology

Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population . It is a cornerstone of public health , and shapes policy decisions and evidence-based practice by identifying risk factors for disease and targets for preventive healthcare . Epidemiologists help with study design, collection, and statistical analysis of data, amend interpretation and dissemination of results (including peer review and occasional systematic review ). Epidemiology has helped develop methodology used in clinical research , public health studies, and, to a lesser extent, basic research in the biological sciences. Major areas of epidemiological study include disease causation, transmission , outbreak investigation, disease surveillance , environmental epidemiology , forensic epidemiology , occupational epidemiology , screening , biomonitoring , and comparisons of treatment effects such as in clinical trials . Epidemiologists rely on other scientific disciplines like biology to better understand disease processes, statistics to make efficient use of the data and draw appropriate conclusions, social sciences to better understand proximate and distal causes, and engineering for exposure assessment . Epidemiology , literally meaning "the study of what is upon the people", is derived from Greek epi 'upon, among', demos 'people, district', and logos 'study, word, discourse' , suggesting that it applies only to human populations. However, the term is widely used in studies of zoological populations (veterinary epidemiology), although the term " epizoology " is available, and it has also been applied to studies of plant populations (botanical or plant disease epidemiology ). The distinction between "epidemic" and "endemic" was first drawn by Hippocrates , to distinguish between diseases that are "visited upon" a population (epidemic) from those that "reside within" a population (endemic). The term "epidemiology" appears to have first been used to describe the study of epidemics in 1802 by the Spanish physician Joaquín de Villalba in Epidemiología Española . Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic . The term epidemiology is now widely applied to cover the description and causation of not only epidemic, infectious disease, but of disease in general, including related conditions. Some examples of topics examined through epidemiology include as high blood pressure, mental illness and obesity . Therefore, this epidemiology is based upon how the pattern of the disease causes change in the function of human beings.The Greek physician Hippocrates , taught by Democritus, was known as the father of medicine , sought a logic to sickness; he is the first person known to have examined the relationships between the occurrence of disease and environmental influences. Hippocrates believed sickness of the human body to be caused by an imbalance of the four humors (black bile, yellow bile, blood, and phlegm). The cure to the sickness was to remove or add the humor in question to balance the body. This belief led to the application of bloodletting and dieting in medicine. He coined the terms endemic (for diseases usually found in some places but not in others) and epidemic (for diseases that are seen at some times but not others). In the middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory that the very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by air, multiply by themselves and to be destroyable by fire. In this way he refuted Galen 's miasma theory (poison gas in sick people). In 1543 he wrote a book De contagione et contagiosis morbis , in which he was the first to promote personal and environmental hygiene to prevent disease. The development of a sufficiently powerful microscope by Antonie van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of disease . [ citation needed ] During the Ming dynasty , Wu Youke (1582–1652) developed the idea that some diseases were caused by transmissible agents, which he called Li Qi (戾气 or pestilential factors) when he observed various epidemics rage around him between 1641 and 1644. His book Wen Yi Lun (瘟疫论, Treatise on Pestilence/Treatise of Epidemic Diseases) can be regarded as the main etiological work that brought forward the concept. His concepts were still being considered in analysing SARS outbreak by WHO in 2004 in the context of traditional Chinese medicine. Another pioneer, Thomas Sydenham (1624–1689), was the first to distinguish the fevers of Londoners in the later 1600s. His theories on cures of fevers met with much resistance from traditional physicians at the time. He was not able to find the initial cause of the smallpox fever he researched and treated. John Graunt , a haberdasher and amateur statistician, published Natural and Political Observations ... upon the Bills of Mortality in 1662. In it, he analysed the mortality rolls in London before the Great Plague , presented one of the first life tables , and reported time trends for many diseases, new and old. He provided statistical evidence for many theories on disease, and also refuted some widespread ideas on them. [ citation needed ] John Snow is famous for his investigations into the causes of the 19th-century cholera epidemics, and is also known as the father of (modern) Epidemiology. He began with noticing the significantly higher death rates in two areas supplied by Southwark Company. His identification of the Broad Street pump as the cause of the Soho epidemic is considered the classic example of epidemiology. Snow used chlorine in an attempt to clean the water and removed the handle; this ended the outbreak. This has been perceived as a major event in the history of public health and regarded as the founding event of the science of epidemiology, having helped shape public health policies around the world. However, Snow's research and preventive measures to avoid further outbreaks were not fully accepted or put into practice until after his death due to the prevailing Miasma Theory of the time, a model of disease in which poor air quality was blamed for illness. This was used to rationalize high rates of infection in impoverished areas instead of addressing the underlying issues of poor nutrition and sanitation, and was proven false by his work. Other pioneers include Danish physician Peter Anton Schleisner , who in 1849 related his work on the prevention of the epidemic of neonatal tetanus on the Vestmanna Islands in Iceland . Another important pioneer was Hungarian physician Ignaz Semmelweis , who in 1847 brought down infant mortality at a Vienna hospital by instituting a disinfection procedure. His findings were published in 1850, but his work was ill-received by his colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon Joseph Lister 'discovered' antiseptics in 1865 in light of the work of Louis Pasteur . [ citation needed ] In the early 20th century, mathematical methods were introduced into epidemiology by Ronald Ross , Janet Lane-Claypon , Anderson Gray McKendrick , and others. In a parallel development during the 1920s, German-Swiss pathologist Max Askanazy and others founded the International Society for Geographical Pathology to systematically investigate the geographical pathology of cancer and other non-infectious diseases across populations in different regions. After World War II, Richard Doll and other non-pathologists joined the field and advanced methods to study cancer, a disease with patterns and mode of occurrences that could not be suitably studied with the methods developed for epidemics of infectious diseases. Geography pathology eventually combined with infectious disease epidemiology to make the field that is epidemiology today. Another breakthrough was the 1954 publication of the results of a British Doctors Study , led by Richard Doll and Austin Bradford Hill , which lent very strong statistical support to the link between tobacco smoking and lung cancer . [ citation needed ] In the late 20th century, with the advancement of biomedical sciences, a number of molecular markers in blood, other biospecimens and environment were identified as predictors of development or risk of a certain disease. Epidemiology research to examine the relationship between these biomarkers analyzed at the molecular level and disease was broadly named " molecular epidemiology ". Specifically, " genetic epidemiology " has been used for epidemiology of germline genetic variation and disease. Genetic variation is typically determined using DNA from peripheral blood leukocytes. [ citation needed ] Since the 2000s, genome-wide association studies (GWAS) have been commonly performed to identify genetic risk factors for many diseases and health conditions. [ citation needed ] While most molecular epidemiology studies are still using conventional disease diagnosis and classification systems, it is increasingly recognized that disease progression represents inherently heterogeneous processes differing from person to person. Conceptually, each individual has a unique disease process different from any other individual ("the unique disease principle"), considering uniqueness of the exposome (a totality of endogenous and exogenous / environmental exposures) and its unique influence on molecular pathologic process in each individual. Studies to examine the relationship between an exposure and molecular pathologic signature of disease (particularly cancer ) became increasingly common throughout the 2000s. However, the use of molecular pathology in epidemiology posed unique challenges, including lack of research guidelines and standardized statistical methodologies, and paucity of interdisciplinary experts and training programs. Furthermore, the concept of disease heterogeneity appears to conflict with the long-standing premise in epidemiology that individuals with the same disease name have similar etiologies and disease processes. To resolve these issues and advance population health science in the era of molecular precision medicine , "molecular pathology" and "epidemiology" was integrated to create a new interdisciplinary field of " molecular pathological epidemiology " (MPE), defined as "epidemiology of molecular pathology and heterogeneity of disease". In MPE, investigators analyze the relationships between (A) environmental, dietary, lifestyle and genetic factors; (B) alterations in cellular or extracellular molecules; and (C) evolution and progression of disease. A better understanding of heterogeneity of disease pathogenesis will further contribute to elucidate etiologies of disease. The MPE approach can be applied to not only neoplastic diseases but also non-neoplastic diseases. The concept and paradigm of MPE have become widespread in the 2010s. [ excessive citations ] By 2012, it was recognized that many pathogens' evolution is rapid enough to be highly relevant to epidemiology, and that therefore much could be gained from an interdisciplinary approach to infectious disease integrating epidemiology and molecular evolution to "inform control strategies, or even patient treatment." Modern epidemiological studies can use advanced statistics and machine learning to create predictive models as well as to define treatment effects. There is increasing recognition that a wide range of modern data sources, many not originating from healthcare or epidemiology, can be used for epidemiological study. Such digital epidemiology can include data from internet searching, mobile phone records and retail sales of drugs. [ citation needed ]In the middle of the 16th century, a doctor from Verona named Girolamo Fracastoro was the first to propose a theory that the very small, unseeable, particles that cause disease were alive. They were considered to be able to spread by air, multiply by themselves and to be destroyable by fire. In this way he refuted Galen 's miasma theory (poison gas in sick people). In 1543 he wrote a book De contagione et contagiosis morbis , in which he was the first to promote personal and environmental hygiene to prevent disease. The development of a sufficiently powerful microscope by Antonie van Leeuwenhoek in 1675 provided visual evidence of living particles consistent with a germ theory of disease . [ citation needed ] During the Ming dynasty , Wu Youke (1582–1652) developed the idea that some diseases were caused by transmissible agents, which he called Li Qi (戾气 or pestilential factors) when he observed various epidemics rage around him between 1641 and 1644. His book Wen Yi Lun (瘟疫论, Treatise on Pestilence/Treatise of Epidemic Diseases) can be regarded as the main etiological work that brought forward the concept. His concepts were still being considered in analysing SARS outbreak by WHO in 2004 in the context of traditional Chinese medicine. Another pioneer, Thomas Sydenham (1624–1689), was the first to distinguish the fevers of Londoners in the later 1600s. His theories on cures of fevers met with much resistance from traditional physicians at the time. He was not able to find the initial cause of the smallpox fever he researched and treated. John Graunt , a haberdasher and amateur statistician, published Natural and Political Observations ... upon the Bills of Mortality in 1662. In it, he analysed the mortality rolls in London before the Great Plague , presented one of the first life tables , and reported time trends for many diseases, new and old. He provided statistical evidence for many theories on disease, and also refuted some widespread ideas on them. [ citation needed ] John Snow is famous for his investigations into the causes of the 19th-century cholera epidemics, and is also known as the father of (modern) Epidemiology. He began with noticing the significantly higher death rates in two areas supplied by Southwark Company. His identification of the Broad Street pump as the cause of the Soho epidemic is considered the classic example of epidemiology. Snow used chlorine in an attempt to clean the water and removed the handle; this ended the outbreak. This has been perceived as a major event in the history of public health and regarded as the founding event of the science of epidemiology, having helped shape public health policies around the world. However, Snow's research and preventive measures to avoid further outbreaks were not fully accepted or put into practice until after his death due to the prevailing Miasma Theory of the time, a model of disease in which poor air quality was blamed for illness. This was used to rationalize high rates of infection in impoverished areas instead of addressing the underlying issues of poor nutrition and sanitation, and was proven false by his work. Other pioneers include Danish physician Peter Anton Schleisner , who in 1849 related his work on the prevention of the epidemic of neonatal tetanus on the Vestmanna Islands in Iceland . Another important pioneer was Hungarian physician Ignaz Semmelweis , who in 1847 brought down infant mortality at a Vienna hospital by instituting a disinfection procedure. His findings were published in 1850, but his work was ill-received by his colleagues, who discontinued the procedure. Disinfection did not become widely practiced until British surgeon Joseph Lister 'discovered' antiseptics in 1865 in light of the work of Louis Pasteur . [ citation needed ] In the early 20th century, mathematical methods were introduced into epidemiology by Ronald Ross , Janet Lane-Claypon , Anderson Gray McKendrick , and others. In a parallel development during the 1920s, German-Swiss pathologist Max Askanazy and others founded the International Society for Geographical Pathology to systematically investigate the geographical pathology of cancer and other non-infectious diseases across populations in different regions. After World War II, Richard Doll and other non-pathologists joined the field and advanced methods to study cancer, a disease with patterns and mode of occurrences that could not be suitably studied with the methods developed for epidemics of infectious diseases. Geography pathology eventually combined with infectious disease epidemiology to make the field that is epidemiology today. Another breakthrough was the 1954 publication of the results of a British Doctors Study , led by Richard Doll and Austin Bradford Hill , which lent very strong statistical support to the link between tobacco smoking and lung cancer . [ citation needed ] In the late 20th century, with the advancement of biomedical sciences, a number of molecular markers in blood, other biospecimens and environment were identified as predictors of development or risk of a certain disease. Epidemiology research to examine the relationship between these biomarkers analyzed at the molecular level and disease was broadly named " molecular epidemiology ". Specifically, " genetic epidemiology " has been used for epidemiology of germline genetic variation and disease. Genetic variation is typically determined using DNA from peripheral blood leukocytes. [ citation needed ]Since the 2000s, genome-wide association studies (GWAS) have been commonly performed to identify genetic risk factors for many diseases and health conditions. [ citation needed ] While most molecular epidemiology studies are still using conventional disease diagnosis and classification systems, it is increasingly recognized that disease progression represents inherently heterogeneous processes differing from person to person. Conceptually, each individual has a unique disease process different from any other individual ("the unique disease principle"), considering uniqueness of the exposome (a totality of endogenous and exogenous / environmental exposures) and its unique influence on molecular pathologic process in each individual. Studies to examine the relationship between an exposure and molecular pathologic signature of disease (particularly cancer ) became increasingly common throughout the 2000s. However, the use of molecular pathology in epidemiology posed unique challenges, including lack of research guidelines and standardized statistical methodologies, and paucity of interdisciplinary experts and training programs. Furthermore, the concept of disease heterogeneity appears to conflict with the long-standing premise in epidemiology that individuals with the same disease name have similar etiologies and disease processes. To resolve these issues and advance population health science in the era of molecular precision medicine , "molecular pathology" and "epidemiology" was integrated to create a new interdisciplinary field of " molecular pathological epidemiology " (MPE), defined as "epidemiology of molecular pathology and heterogeneity of disease". In MPE, investigators analyze the relationships between (A) environmental, dietary, lifestyle and genetic factors; (B) alterations in cellular or extracellular molecules; and (C) evolution and progression of disease. A better understanding of heterogeneity of disease pathogenesis will further contribute to elucidate etiologies of disease. The MPE approach can be applied to not only neoplastic diseases but also non-neoplastic diseases. The concept and paradigm of MPE have become widespread in the 2010s. [ excessive citations ] By 2012, it was recognized that many pathogens' evolution is rapid enough to be highly relevant to epidemiology, and that therefore much could be gained from an interdisciplinary approach to infectious disease integrating epidemiology and molecular evolution to "inform control strategies, or even patient treatment." Modern epidemiological studies can use advanced statistics and machine learning to create predictive models as well as to define treatment effects. There is increasing recognition that a wide range of modern data sources, many not originating from healthcare or epidemiology, can be used for epidemiological study. Such digital epidemiology can include data from internet searching, mobile phone records and retail sales of drugs. [ citation needed ]Epidemiologists employ a range of study designs from the observational to experimental and generally categorized as descriptive (involving the assessment of data covering time, place, and person), analytic (aiming to further examine known associations or hypothesized relationships), and experimental (a term often equated with clinical or community trials of treatments and other interventions). In observational studies, nature is allowed to "take its course", as epidemiologists observe from the sidelines. Conversely, in experimental studies, the epidemiologist is the one in control of all of the factors entering a certain case study. Epidemiological studies are aimed, where possible, at revealing unbiased relationships between exposures such as alcohol or smoking, biological agents , stress , or chemicals to mortality or morbidity . The identification of causal relationships between these exposures and outcomes is an important aspect of epidemiology. Modern epidemiologists use informatics and infodemiology as a tools. [ citation needed ] Observational studies have two components, descriptive and analytical. Descriptive observations pertain to the "who, what, where and when of health-related state occurrence". However, analytical observations deal more with the 'how' of a health-related event. Experimental epidemiology contains three case types: randomized controlled trials (often used for a new medicine or drug testing), field trials (conducted on those at a high risk of contracting a disease), and community trials (research on social originating diseases). The term 'epidemiologic triad' is used to describe the intersection of Host , Agent , and Environment in analyzing an outbreak. [ citation needed ] Case-series may refer to the qualitative study of the experience of a single patient, or small group of patients with a similar diagnosis, or to a statistical factor with the potential to produce illness with periods when they are unexposed. The former type of study is purely descriptive and cannot be used to make inferences about the general population of patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a disease or a patient's history, may lead to a formulation of a new hypothesis. Using the data from the series, analytic studies could be done to investigate possible causal factors. These can include case-control studies or prospective studies. A case-control study would involve matching comparable controls without the disease to the cases in the series. A prospective study would involve following the case series over time to evaluate the disease's natural history. The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively used in the study of adverse reactions to vaccination and has been shown in some circumstances to provide statistical power comparable to that available in cohort studies. [ citation needed ] Case-control studies select subjects based on their disease status. It is a retrospective study. A group of individuals that are disease positive (the "case" group) is compared with a group of disease negative individuals (the "control" group). The control group should ideally come from the same population that gave rise to the cases. The case-control study looks back through time at potential exposures that both groups (cases and controls) may have encountered. A 2×2 table is constructed, displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association is the odds ratio (OR), which is the ratio of the odds of exposure in the cases (A/C) to the odds of exposure in the controls (B/D), i.e. OR = (AD/BC). [ citation needed ] If the OR is significantly greater than 1, then the conclusion is "those with the disease are more likely to have been exposed," whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than one, then this suggests that the exposure is a protective factor in the causation of the disease. Case-control studies are usually faster and more cost-effective than cohort studies but are sensitive to bias (such as recall bias and selection bias ). The main challenge is to identify the appropriate control group; the distribution of exposure among the control group should be representative of the distribution in the population that gave rise to the cases. This can be achieved by drawing a random sample from the original population at risk. This has as a consequence that the control group can contain people with the disease under study when the disease has a high attack rate in a population. [ citation needed ] A major drawback for case control studies is that, in order to be considered to be statistically significant, the minimum number of cases required at the 95% confidence interval is related to the odds ratio by the equation: where N is the ratio of cases to controls. As the odds ratio approaches 1, the number of cases required for statistical significance grows towards infinity; rendering case-control studies all but useless for low odds ratios. For instance, for an odds ratio of 1.5 and cases = controls, the table shown above would look like this: For an odds ratio of 1.1: Cohort studies select subjects based on their exposure status. The study subjects should be at risk of the outcome under investigation at the beginning of the cohort study; this usually means that they should be disease free when the cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung cancer. The same 2×2 table is constructed as with the case control study. However, the point estimate generated is the relative risk (RR), which is the probability of disease for a person in the exposed group, P e = A / ( A + B ) over the probability of disease for a person in the unexposed group, P u = C / ( C + D ), i.e. RR = P e / P u . As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure were more likely to develop the disease." Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where subjects are selected based on disease status. Temporality can be established in a prospective study, and confounders are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to follow-up based on the long time period over which the cohort is followed. Cohort studies also are limited by the same equation for number of cases as for cohort studies, but, if the base incidence rate in the study population is very low, the number of cases required is reduced by 1 ⁄ 2 .Case-series may refer to the qualitative study of the experience of a single patient, or small group of patients with a similar diagnosis, or to a statistical factor with the potential to produce illness with periods when they are unexposed. The former type of study is purely descriptive and cannot be used to make inferences about the general population of patients with that disease. These types of studies, in which an astute clinician identifies an unusual feature of a disease or a patient's history, may lead to a formulation of a new hypothesis. Using the data from the series, analytic studies could be done to investigate possible causal factors. These can include case-control studies or prospective studies. A case-control study would involve matching comparable controls without the disease to the cases in the series. A prospective study would involve following the case series over time to evaluate the disease's natural history. The latter type, more formally described as self-controlled case-series studies, divide individual patient follow-up time into exposed and unexposed periods and use fixed-effects Poisson regression processes to compare the incidence rate of a given outcome between exposed and unexposed periods. This technique has been extensively used in the study of adverse reactions to vaccination and has been shown in some circumstances to provide statistical power comparable to that available in cohort studies. [ citation needed ]Case-control studies select subjects based on their disease status. It is a retrospective study. A group of individuals that are disease positive (the "case" group) is compared with a group of disease negative individuals (the "control" group). The control group should ideally come from the same population that gave rise to the cases. The case-control study looks back through time at potential exposures that both groups (cases and controls) may have encountered. A 2×2 table is constructed, displaying exposed cases (A), exposed controls (B), unexposed cases (C) and unexposed controls (D). The statistic generated to measure association is the odds ratio (OR), which is the ratio of the odds of exposure in the cases (A/C) to the odds of exposure in the controls (B/D), i.e. OR = (AD/BC). [ citation needed ] If the OR is significantly greater than 1, then the conclusion is "those with the disease are more likely to have been exposed," whereas if it is close to 1 then the exposure and disease are not likely associated. If the OR is far less than one, then this suggests that the exposure is a protective factor in the causation of the disease. Case-control studies are usually faster and more cost-effective than cohort studies but are sensitive to bias (such as recall bias and selection bias ). The main challenge is to identify the appropriate control group; the distribution of exposure among the control group should be representative of the distribution in the population that gave rise to the cases. This can be achieved by drawing a random sample from the original population at risk. This has as a consequence that the control group can contain people with the disease under study when the disease has a high attack rate in a population. [ citation needed ] A major drawback for case control studies is that, in order to be considered to be statistically significant, the minimum number of cases required at the 95% confidence interval is related to the odds ratio by the equation: where N is the ratio of cases to controls. As the odds ratio approaches 1, the number of cases required for statistical significance grows towards infinity; rendering case-control studies all but useless for low odds ratios. For instance, for an odds ratio of 1.5 and cases = controls, the table shown above would look like this: For an odds ratio of 1.1:Cohort studies select subjects based on their exposure status. The study subjects should be at risk of the outcome under investigation at the beginning of the cohort study; this usually means that they should be disease free when the cohort study starts. The cohort is followed through time to assess their later outcome status. An example of a cohort study would be the investigation of a cohort of smokers and non-smokers over time to estimate the incidence of lung cancer. The same 2×2 table is constructed as with the case control study. However, the point estimate generated is the relative risk (RR), which is the probability of disease for a person in the exposed group, P e = A / ( A + B ) over the probability of disease for a person in the unexposed group, P u = C / ( C + D ), i.e. RR = P e / P u . As with the OR, a RR greater than 1 shows association, where the conclusion can be read "those with the exposure were more likely to develop the disease." Prospective studies have many benefits over case control studies. The RR is a more powerful effect measure than the OR, as the OR is just an estimation of the RR, since true incidence cannot be calculated in a case control study where subjects are selected based on disease status. Temporality can be established in a prospective study, and confounders are more easily controlled for. However, they are more costly, and there is a greater chance of losing subjects to follow-up based on the long time period over which the cohort is followed. Cohort studies also are limited by the same equation for number of cases as for cohort studies, but, if the base incidence rate in the study population is very low, the number of cases required is reduced by 1 ⁄ 2 .Although epidemiology is sometimes viewed as a collection of statistical tools used to elucidate the associations of exposures to health outcomes, a deeper understanding of this science is that of discovering causal relationships. " Correlation does not imply causation " is a common theme for much of the epidemiological literature. For epidemiologists, the key is in the term inference . Correlation, or at least association between two variables, is a necessary but not sufficient criterion for the inference that one variable causes the other. Epidemiologists use gathered data and a broad range of biomedical and psychosocial theories in an iterative way to generate or expand theory, to test hypotheses, and to make educated, informed assertions about which relationships are causal, and about exactly how they are causal. Epidemiologists emphasize that the " one cause – one effect " understanding is a simplistic mis-belief. Most outcomes, whether disease or death, are caused by a chain or web consisting of many component causes. Causes can be distinguished as necessary, sufficient or probabilistic conditions. If a necessary condition can be identified and controlled (e.g., antibodies to a disease agent, energy in an injury), the harmful outcome can be avoided (Robertson, 2015). One tool regularly used to conceptualize the multicausality associated with disease is the causal pie model . In 1965, Austin Bradford Hill proposed a series of considerations to help assess evidence of causation, which have come to be commonly known as the " Bradford Hill criteria ". In contrast to the explicit intentions of their author, Hill's considerations are now sometimes taught as a checklist to be implemented for assessing causality. Hill himself said "None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required sine qua non ." Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case: Epidemiology is concerned with the incidence of disease in populations and does not address the question of the cause of an individual's disease. This question, sometimes referred to as specific causation, is beyond the domain of the science of epidemiology. Epidemiology has its limits at the point where an inference is made that the relationship between an agent and a disease is causal (general causation) and where the magnitude of excess risk attributed to the agent has been determined; that is, epidemiology addresses whether an agent can cause disease, not whether an agent did cause a specific plaintiff's disease. In United States law, epidemiology alone cannot prove that a causal association does not exist in general. Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference that a causal association does exist, based upon a balance of probability . The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury in individuals or groups of individuals in instances in which causation is disputed or is unclear, for presentation in legal settings.In 1965, Austin Bradford Hill proposed a series of considerations to help assess evidence of causation, which have come to be commonly known as the " Bradford Hill criteria ". In contrast to the explicit intentions of their author, Hill's considerations are now sometimes taught as a checklist to be implemented for assessing causality. Hill himself said "None of my nine viewpoints can bring indisputable evidence for or against the cause-and-effect hypothesis and none can be required sine qua non ." Epidemiological studies can only go to prove that an agent could have caused, but not that it did cause, an effect in any particular case: Epidemiology is concerned with the incidence of disease in populations and does not address the question of the cause of an individual's disease. This question, sometimes referred to as specific causation, is beyond the domain of the science of epidemiology. Epidemiology has its limits at the point where an inference is made that the relationship between an agent and a disease is causal (general causation) and where the magnitude of excess risk attributed to the agent has been determined; that is, epidemiology addresses whether an agent can cause disease, not whether an agent did cause a specific plaintiff's disease. In United States law, epidemiology alone cannot prove that a causal association does not exist in general. Conversely, it can be (and is in some circumstances) taken by US courts, in an individual case, to justify an inference that a causal association does exist, based upon a balance of probability . The subdiscipline of forensic epidemiology is directed at the investigation of specific causation of disease or injury in individuals or groups of individuals in instances in which causation is disputed or is unclear, for presentation in legal settings.Epidemiological practice and the results of epidemiological analysis make a significant contribution to emerging population-based health management frameworks. Population-based health management encompasses the ability to: Assess the health states and health needs of a target population; Implement and evaluate interventions that are designed to improve the health of that population; and Efficiently and effectively provide care for members of that population in a way that is consistent with the community's cultural, policy and health resource values. Modern population-based health management is complex, requiring a multiple set of skills (medical, political, technological, mathematical, etc.) of which epidemiological practice and analysis is a core component, that is unified with management science to provide efficient and effective health care and health guidance to a population. This task requires the forward-looking ability of modern risk management approaches that transform health risk factors, incidence, prevalence and mortality statistics (derived from epidemiological analysis) into management metrics that not only guide how a health system responds to current population health issues but also how a health system can be managed to better respond to future potential population health issues. Examples of organizations that use population-based health management that leverage the work and results of epidemiological practice include Canadian Strategy for Cancer Control, Health Canada Tobacco Control Programs, Rick Hansen Foundation, Canadian Tobacco Control Research Initiative. Each of these organizations uses a population-based health management framework called Life at Risk that combines epidemiological quantitative analysis with demographics, health agency operational research and economics to perform: Population Life Impacts Simulations : Measurement of the future potential impact of disease upon the population with respect to new disease cases, prevalence, premature death as well as potential years of life lost from disability and death; Labour Force Life Impacts Simulations : Measurement of the future potential impact of disease upon the labour force with respect to new disease cases, prevalence, premature death and potential years of life lost from disability and death; Economic Impacts of Disease Simulations : Measurement of the future potential impact of disease upon private sector disposable income impacts (wages, corporate profits, private health care costs) and public sector disposable income impacts (personal income tax, corporate income tax, consumption taxes, publicly funded health care costs).Applied epidemiology is the practice of using epidemiological methods to protect or improve the health of a population. Applied field epidemiology can include investigating communicable and non-communicable disease outbreaks, mortality and morbidity rates, and nutritional status, among other indicators of health, with the purpose of communicating the results to those who can implement appropriate policies or disease control measures. As the surveillance and reporting of diseases and other health factors become increasingly difficult in humanitarian crisis situations, the methodologies used to report the data are compromised. One study found that less than half (42.4%) of nutrition surveys sampled from humanitarian contexts correctly calculated the prevalence of malnutrition and only one-third (35.3%) of the surveys met the criteria for quality. Among the mortality surveys, only 3.2% met the criteria for quality. As nutritional status and mortality rates help indicate the severity of a crisis, the tracking and reporting of these health factors is crucial. Vital registries are usually the most effective ways to collect data, but in humanitarian contexts these registries can be non-existent, unreliable, or inaccessible. As such, mortality is often inaccurately measured using either prospective demographic surveillance or retrospective mortality surveys. Prospective demographic surveillance requires much manpower and is difficult to implement in a spread-out population. Retrospective mortality surveys are prone to selection and reporting biases. Other methods are being developed, but are not common practice yet. As the surveillance and reporting of diseases and other health factors become increasingly difficult in humanitarian crisis situations, the methodologies used to report the data are compromised. One study found that less than half (42.4%) of nutrition surveys sampled from humanitarian contexts correctly calculated the prevalence of malnutrition and only one-third (35.3%) of the surveys met the criteria for quality. Among the mortality surveys, only 3.2% met the criteria for quality. As nutritional status and mortality rates help indicate the severity of a crisis, the tracking and reporting of these health factors is crucial. Vital registries are usually the most effective ways to collect data, but in humanitarian contexts these registries can be non-existent, unreliable, or inaccessible. As such, mortality is often inaccurately measured using either prospective demographic surveillance or retrospective mortality surveys. Prospective demographic surveillance requires much manpower and is difficult to implement in a spread-out population. Retrospective mortality surveys are prone to selection and reporting biases. Other methods are being developed, but are not common practice yet. The concept of waves in epidemics has implications especially for communicable diseases . A working definition for the term "epidemic wave" is based on two key features: 1) it comprises periods of upward or downward trends, and 2) these increases or decreases must be substantial and sustained over a period of time, in order to distinguish them from minor fluctuations or reporting errors. The use of a consistent scientific definition is to provide a consistent language that can be used to communicate about and understand the progression of the COVID-19 pandemic, which would aid healthcare organizations and policymakers in resource planning and allocation. Different fields in epidemiology have different levels of validity. One way to assess the validity of findings is the ratio of false-positives (claimed effects that are not correct) to false-negatives (studies which fail to support a true effect). In genetic epidemiology , candidate-gene studies may produce over 100 false-positive findings for each false-negative. By contrast genome-wide association appear close to the reverse, with only one false positive for every 100 or more false-negatives. This ratio has improved over time in genetic epidemiology, as the field has adopted stringent criteria. By contrast, other epidemiological fields have not required such rigorous reporting and are much less reliable as a result. Random error is the result of fluctuations around a true value because of sampling variability. Random error is just that: random. It can occur during data collection, coding, transfer, or analysis. Examples of random errors include poorly worded questions, a misunderstanding in interpreting an individual answer from a particular respondent, or a typographical error during coding. Random error affects measurement in a transient, inconsistent manner and it is impossible to correct for random error. There is a random error in all sampling procedures – sampling error . [ citation needed ] Precision in epidemiological variables is a measure of random error. Precision is also inversely related to random error, so that to reduce random error is to increase precision. Confidence intervals are computed to demonstrate the precision of relative risk estimates. The narrower the confidence interval, the more precise the relative risk estimate. There are two basic ways to reduce random error in an epidemiological study . The first is to increase the sample size of the study. In other words, add more subjects to your study. The second is to reduce the variability in measurement in the study. This might be accomplished by using a more precise measuring device or by increasing the number of measurements. Note, that if sample size or number of measurements are increased, or a more precise measuring tool is purchased, the costs of the study are usually increased. There is usually an uneasy balance between the need for adequate precision and the practical issue of study cost. A systematic error or bias occurs when there is a difference between the true value (in the population) and the observed value (in the study) from any cause other than sampling variability. An example of systematic error is if, unknown to you, the pulse oximeter you are using is set incorrectly and adds two points to the true value each time a measurement is taken. The measuring device could be precise but not accurate . Because the error happens in every instance, it is systematic. Conclusions you draw based on that data will still be incorrect. But the error can be reproduced in the future (e.g., by using the same mis-set instrument). A mistake in coding that affects all responses for that particular question is another example of a systematic error. The validity of a study is dependent on the degree of systematic error. Validity is usually separated into two components: Selection bias occurs when study subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with both the exposure and outcome of interest. For instance, it has repeatedly been noted that cigarette smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires.) Such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome between the two response groups. Information bias is bias arising from systematic error in the assessment of a variable. An example of this is recall bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found that 28% of the former, but only 20% of the latter, reported exposure to drugs which could not be substantiated either in earlier prospective interviews or in other health records". In this example, recall bias probably occurred as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report previous exposures. Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous factors, referred to as confounders, with the main effect(s) of interest. A more recent definition of confounding invokes the notion of counterfactual effects. According to this view, when one observes an outcome of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure X = 1 for every unit of the population) the risk of this event will be R A1 . The counterfactual or unobserved risk R A0 corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. X = 0 for every unit of the population). The true effect of exposure therefore is: R A1 − R A0 (if one is interested in risk differences) or R A1 / R A0 (if one is interested in relative risk). Since the counterfactual risk R A0 is unobservable we approximate it using a second population B and we actually measure the following relations: R A1 − R B0 or R A1 / R B0 . In this situation, confounding occurs when R A0 ≠R B0 . (NB: Example assumes binary outcome and exposure variables.) Some epidemiologists prefer to think of confounding separately from common categorizations of bias since, unlike selection and information bias, confounding stems from real causal effects. The concept of waves in epidemics has implications especially for communicable diseases . A working definition for the term "epidemic wave" is based on two key features: 1) it comprises periods of upward or downward trends, and 2) these increases or decreases must be substantial and sustained over a period of time, in order to distinguish them from minor fluctuations or reporting errors. The use of a consistent scientific definition is to provide a consistent language that can be used to communicate about and understand the progression of the COVID-19 pandemic, which would aid healthcare organizations and policymakers in resource planning and allocation.Different fields in epidemiology have different levels of validity. One way to assess the validity of findings is the ratio of false-positives (claimed effects that are not correct) to false-negatives (studies which fail to support a true effect). In genetic epidemiology , candidate-gene studies may produce over 100 false-positive findings for each false-negative. By contrast genome-wide association appear close to the reverse, with only one false positive for every 100 or more false-negatives. This ratio has improved over time in genetic epidemiology, as the field has adopted stringent criteria. By contrast, other epidemiological fields have not required such rigorous reporting and are much less reliable as a result. Random error is the result of fluctuations around a true value because of sampling variability. Random error is just that: random. It can occur during data collection, coding, transfer, or analysis. Examples of random errors include poorly worded questions, a misunderstanding in interpreting an individual answer from a particular respondent, or a typographical error during coding. Random error affects measurement in a transient, inconsistent manner and it is impossible to correct for random error. There is a random error in all sampling procedures – sampling error . [ citation needed ] Precision in epidemiological variables is a measure of random error. Precision is also inversely related to random error, so that to reduce random error is to increase precision. Confidence intervals are computed to demonstrate the precision of relative risk estimates. The narrower the confidence interval, the more precise the relative risk estimate. There are two basic ways to reduce random error in an epidemiological study . The first is to increase the sample size of the study. In other words, add more subjects to your study. The second is to reduce the variability in measurement in the study. This might be accomplished by using a more precise measuring device or by increasing the number of measurements. Note, that if sample size or number of measurements are increased, or a more precise measuring tool is purchased, the costs of the study are usually increased. There is usually an uneasy balance between the need for adequate precision and the practical issue of study cost.A systematic error or bias occurs when there is a difference between the true value (in the population) and the observed value (in the study) from any cause other than sampling variability. An example of systematic error is if, unknown to you, the pulse oximeter you are using is set incorrectly and adds two points to the true value each time a measurement is taken. The measuring device could be precise but not accurate . Because the error happens in every instance, it is systematic. Conclusions you draw based on that data will still be incorrect. But the error can be reproduced in the future (e.g., by using the same mis-set instrument). A mistake in coding that affects all responses for that particular question is another example of a systematic error. The validity of a study is dependent on the degree of systematic error. Validity is usually separated into two components: Selection bias occurs when study subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with both the exposure and outcome of interest. For instance, it has repeatedly been noted that cigarette smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires.) Such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome between the two response groups. Information bias is bias arising from systematic error in the assessment of a variable. An example of this is recall bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found that 28% of the former, but only 20% of the latter, reported exposure to drugs which could not be substantiated either in earlier prospective interviews or in other health records". In this example, recall bias probably occurred as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report previous exposures. Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous factors, referred to as confounders, with the main effect(s) of interest. A more recent definition of confounding invokes the notion of counterfactual effects. According to this view, when one observes an outcome of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure X = 1 for every unit of the population) the risk of this event will be R A1 . The counterfactual or unobserved risk R A0 corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. X = 0 for every unit of the population). The true effect of exposure therefore is: R A1 − R A0 (if one is interested in risk differences) or R A1 / R A0 (if one is interested in relative risk). Since the counterfactual risk R A0 is unobservable we approximate it using a second population B and we actually measure the following relations: R A1 − R B0 or R A1 / R B0 . In this situation, confounding occurs when R A0 ≠R B0 . (NB: Example assumes binary outcome and exposure variables.) Some epidemiologists prefer to think of confounding separately from common categorizations of bias since, unlike selection and information bias, confounding stems from real causal effects. Selection bias occurs when study subjects are selected or become part of the study as a result of a third, unmeasured variable which is associated with both the exposure and outcome of interest. For instance, it has repeatedly been noted that cigarette smokers and non smokers tend to differ in their study participation rates. (Sackett D cites the example of Seltzer et al., in which 85% of non smokers and 67% of smokers returned mailed questionnaires.) Such a difference in response will not lead to bias if it is not also associated with a systematic difference in outcome between the two response groups.Information bias is bias arising from systematic error in the assessment of a variable. An example of this is recall bias. A typical example is again provided by Sackett in his discussion of a study examining the effect of specific exposures on fetal health: "in questioning mothers whose recent pregnancies had ended in fetal death or malformation (cases) and a matched group of mothers whose pregnancies ended normally (controls) it was found that 28% of the former, but only 20% of the latter, reported exposure to drugs which could not be substantiated either in earlier prospective interviews or in other health records". In this example, recall bias probably occurred as a result of women who had had miscarriages having an apparent tendency to better recall and therefore report previous exposures.Confounding has traditionally been defined as bias arising from the co-occurrence or mixing of effects of extraneous factors, referred to as confounders, with the main effect(s) of interest. A more recent definition of confounding invokes the notion of counterfactual effects. According to this view, when one observes an outcome of interest, say Y=1 (as opposed to Y=0), in a given population A which is entirely exposed (i.e. exposure X = 1 for every unit of the population) the risk of this event will be R A1 . The counterfactual or unobserved risk R A0 corresponds to the risk which would have been observed if these same individuals had been unexposed (i.e. X = 0 for every unit of the population). The true effect of exposure therefore is: R A1 − R A0 (if one is interested in risk differences) or R A1 / R A0 (if one is interested in relative risk). Since the counterfactual risk R A0 is unobservable we approximate it using a second population B and we actually measure the following relations: R A1 − R B0 or R A1 / R B0 . In this situation, confounding occurs when R A0 ≠R B0 . (NB: Example assumes binary outcome and exposure variables.) Some epidemiologists prefer to think of confounding separately from common categorizations of bias since, unlike selection and information bias, confounding stems from real causal effects. Few universities have offered epidemiology as a course of study at the undergraduate level. One notable undergraduate program exists at Johns Hopkins University , where students who major in public health can take graduate-level courses, including epidemiology, during their senior year at the Bloomberg School of Public Health . Although epidemiologic research is conducted by individuals from diverse disciplines, including clinically trained professionals such as physicians, formal training is available through Masters or Doctoral programs including Master of Public Health (MPH), Master of Science of Epidemiology (MSc.), Doctor of Public Health (DrPH), Doctor of Pharmacy (PharmD), Doctor of Philosophy (PhD), Doctor of Science (ScD). Many other graduate programs, e.g., Doctor of Social Work (DSW), Doctor of Clinical Practice (DClinP), Doctor of Podiatric Medicine (DPM), Doctor of Veterinary Medicine (DVM), Doctor of Nursing Practice (DNP), Doctor of Physical Therapy (DPT), or for clinically trained physicians, Doctor of Medicine (MD) or Bachelor of Medicine and Surgery (MBBS or MBChB) and Doctor of Osteopathic Medicine (DO), include some training in epidemiologic research or related topics, but this training is generally substantially less than offered in training programs focused on epidemiology or public health. Reflecting the strong historical tie between epidemiology and medicine, formal training programs may be set in either schools of public health or medical schools. As public health/health protection practitioners, epidemiologists work in a number of different settings. Some epidemiologists work 'in the field'; i.e., in the community, commonly in a public health/health protection service, and are often at the forefront of investigating and combating disease outbreaks. Others work for non-profit organizations, universities, hospitals and larger government entities such as state and local health departments, various Ministries of Health, Doctors without Borders , the Centers for Disease Control and Prevention (CDC), the Health Protection Agency , the World Health Organization (WHO), or the Public Health Agency of Canada . Epidemiologists can also work in for-profit organizations such as pharmaceutical and medical device companies in groups such as market research or clinical development. An April 2020 University of Southern California article noted that "The coronavirus epidemic ... thrust epidemiology – the study of the incidence, distribution and control of disease in a population – to the forefront of scientific disciplines across the globe and even made temporary celebrities out of some of its practitioners." An April 2020 University of Southern California article noted that "The coronavirus epidemic ... thrust epidemiology – the study of the incidence, distribution and control of disease in a population – to the forefront of scientific disciplines across the globe and even made temporary celebrities out of some of its practitioners."

Wiki

Chikungunya

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

Jonas Salk

Medical research virology epidemiology Jonas Edward Salk ( / s ɔː l k / ; born Jonas Salk ; October 28, 1914 – June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines . He was born in New York City and attended the City College of New York and New York University School of Medicine . In 1947, Salk accepted a professorship at the University of Pittsburgh School of Medicine , where he undertook a project beginning in 1948 to determine the number of different types of poliovirus . For the next seven years, Salk devoted himself to developing a vaccine against polio . Salk was immediately hailed as a "miracle worker" when the vaccine's success was first made public in April 1955, and chose to not patent the vaccine or seek any profit from it in order to maximize its global distribution. The National Foundation for Infantile Paralysis and the University of Pittsburgh looked into patenting the vaccine, but since Salk's techniques were not novel, their patent attorney said, "If there were any patentable novelty to be found in this phase it would lie within an extremely narrow scope and would be of doubtful value." An immediate rush to vaccinate began in the United States and around the world. Many countries began polio immunization campaigns using Salk's vaccine, including Canada, Sweden, Denmark, Norway, West Germany, the Netherlands, Switzerland, and Belgium. By 1959, the Salk vaccine had reached about 90 countries. An attenuated live oral polio vaccine was developed by Albert Sabin , coming into commercial use in 1961. Less than 25 years after the release of Salk's vaccine, domestic transmission of polio had been eliminated in the United States. In 1963, Salk founded the Salk Institute for Biological Studies in La Jolla , California, which is today a center for medical and scientific research. He continued to conduct research and publish books in his later years, focusing in his last years on the search for a vaccine against HIV . Salk campaigned vigorously for mandatory vaccination throughout the rest of his life, calling the universal vaccination of children against disease a "moral commitment". Salk's personal papers are today stored in Geisel Library at the University of California, San Diego . Jonas Salk was born in New York City to Daniel and Dora (née Press) Salk. His parents were Jewish; Daniel was born in New Jersey to immigrant parents, and Dora, who was born in Minsk , emigrated to the United States when she was twelve. Salk's parents did not receive extensive formal education. Jonas had two younger brothers, Herman and Lee , a child psychologist . The family moved from East Harlem to 853 Elsmere Place in the Bronx , with some time spent in Queens at 439 Beach 69th Street, Arverne . When he was 13, Salk entered Townsend Harris High School , a public school for intellectually gifted students. Named after the founder of City College of New York (CCNY), it was "a launching pad for the talented sons of immigrant parents who lacked the money—and pedigree—to attend a top private school", according to David Oshinsky, his biographer. In high school, "he was known as a perfectionist...who read everything he could lay his hands on," according to one of his fellow students. Students had to cram a four-year curriculum into just three years. As a result, most dropped out or flunked out, despite the school's motto "study, study, study." Of the students who graduated, however, most had the grades to enroll in CCNY, then noted for being a highly competitive college. : 96 Salk enrolled in CCNY, where he earned a Bachelor of Science degree in chemistry in 1934. Oshinsky writes that "for working-class immigrant families, City College represented the apex of public higher education. Getting in was tough, but tuition was free. Competition was intense, but the rules were fairly applied. No one got an advantage based on an accident of birth." At his mother's urging, he put aside aspirations of becoming a lawyer and instead concentrated on classes necessary for admission to medical school. However, according to Oshinsky, the facilities at City College were "barely second rate." There were no research laboratories. The library was inadequate. The faculty contained few noted scholars. "What made the place special," he writes, "was the student body that had fought so hard to get there... driven by their parents.... From these ranks, of the 1930s and 1940s, emerged a wealth of intellectual talent, including more Nobel Prize winners—eight—and PhD recipients than any other public college except the University of California at Berkeley ." Salk entered CCNY at the age of 15, a "common age for a freshman who had skipped multiple grades along the way." : 98 As a child, Salk did not show any interest in medicine or science in general. He said in an interview with the Academy of Achievement , "As a child I was not interested in science. I was merely interested in things human, the human side of nature, if you like, and I continue to be interested in that." After graduating from City College of New York, Salk enrolled in New York University School of Medicine . According to Oshinsky, NYU based its modest reputation on famous alumni, such as Walter Reed , who helped conquer yellow fever . Tuition was "comparatively low, better still, it did not discriminate against Jews... while most of the surrounding medical schools— Cornell , Columbia , University of Pennsylvania , and Yale —had rigid quotas in place." Yale, for example, accepted 76 applicants in 1935 out of a pool of 501. Although 200 of the applicants were Jewish, only five got in. : 98 During his years at New York University Medical School , Salk worked as a laboratory technician during the school year and as a camp counselor in the summer. During Salk's medical studies, he stood out from his peers, according to Bookchin, "not just because of his continued academic prowess—he was Alpha Omega Alpha , the Phi Beta Kappa Society of medical education—but because he had decided he did not want to practice medicine." Instead, he became absorbed in research, even taking a year off to study biochemistry . He later focused more of his studies on bacteriology , which had replaced medicine as his primary interest. He said his desire was to help humankind in general rather than single patients. "It was the laboratory work, in particular, that gave new direction to his life." Salk has said, "My intention was to go to medical school, and then become a medical scientist. I did not intend to practice medicine, although in medical school, and in my internship, I did all the things that were necessary to qualify me in that regard. I had opportunities along the way to drop the idea of medicine and go into science. At one point at the end of my first year of medical school, I received an opportunity to spend a year in research and teaching in biochemistry, which I did. And at the end of that year, I was told that I could, if I wished, switch and get a Ph.D. in biochemistry, but my preference was to stay with medicine. And, I believe that this is all linked to my original ambition, or desire, which was to be of some help to humankind, so to speak, in a larger sense than just on a one-to-one basis." In his last year of medical school, Salk said, "I had an opportunity to spend time in elective periods in my last year in medical school, in a laboratory that was involved in studies on influenza. The influenza virus had just been discovered about a few years before that. And, I saw the opportunity at that time to test the question as to whether we could destroy the virus infectivity and still immunize. And so, by carefully designed experiments, we found it was possible to do so." In 1941, during his postgraduate work in virology, Salk chose a two-month elective to work in the Thomas Francis ' laboratory at the University of Michigan . Francis had recently joined the faculty of the medical school after working for the Rockefeller Foundation , where he had discovered the type B influenza virus . According to Bookchin, "the two-month stint in Francis's lab was Salk's first introduction to the world of virology —and he was hooked." : 25 After graduating from medical school, Salk began his residency at New York's prestigious Mount Sinai Hospital , where he again worked in Francis's laboratory. Salk then worked at the University of Michigan School of Public Health with Francis, on an army-commissioned project in Michigan to develop an influenza vaccine. He and Francis eventually perfected a vaccine that was soon widely used at army bases, where Salk discovered and isolated one of the strains of influenza that was included in the final vaccine. : 26Salk enrolled in CCNY, where he earned a Bachelor of Science degree in chemistry in 1934. Oshinsky writes that "for working-class immigrant families, City College represented the apex of public higher education. Getting in was tough, but tuition was free. Competition was intense, but the rules were fairly applied. No one got an advantage based on an accident of birth." At his mother's urging, he put aside aspirations of becoming a lawyer and instead concentrated on classes necessary for admission to medical school. However, according to Oshinsky, the facilities at City College were "barely second rate." There were no research laboratories. The library was inadequate. The faculty contained few noted scholars. "What made the place special," he writes, "was the student body that had fought so hard to get there... driven by their parents.... From these ranks, of the 1930s and 1940s, emerged a wealth of intellectual talent, including more Nobel Prize winners—eight—and PhD recipients than any other public college except the University of California at Berkeley ." Salk entered CCNY at the age of 15, a "common age for a freshman who had skipped multiple grades along the way." : 98 As a child, Salk did not show any interest in medicine or science in general. He said in an interview with the Academy of Achievement , "As a child I was not interested in science. I was merely interested in things human, the human side of nature, if you like, and I continue to be interested in that."After graduating from City College of New York, Salk enrolled in New York University School of Medicine . According to Oshinsky, NYU based its modest reputation on famous alumni, such as Walter Reed , who helped conquer yellow fever . Tuition was "comparatively low, better still, it did not discriminate against Jews... while most of the surrounding medical schools— Cornell , Columbia , University of Pennsylvania , and Yale —had rigid quotas in place." Yale, for example, accepted 76 applicants in 1935 out of a pool of 501. Although 200 of the applicants were Jewish, only five got in. : 98 During his years at New York University Medical School , Salk worked as a laboratory technician during the school year and as a camp counselor in the summer. During Salk's medical studies, he stood out from his peers, according to Bookchin, "not just because of his continued academic prowess—he was Alpha Omega Alpha , the Phi Beta Kappa Society of medical education—but because he had decided he did not want to practice medicine." Instead, he became absorbed in research, even taking a year off to study biochemistry . He later focused more of his studies on bacteriology , which had replaced medicine as his primary interest. He said his desire was to help humankind in general rather than single patients. "It was the laboratory work, in particular, that gave new direction to his life." Salk has said, "My intention was to go to medical school, and then become a medical scientist. I did not intend to practice medicine, although in medical school, and in my internship, I did all the things that were necessary to qualify me in that regard. I had opportunities along the way to drop the idea of medicine and go into science. At one point at the end of my first year of medical school, I received an opportunity to spend a year in research and teaching in biochemistry, which I did. And at the end of that year, I was told that I could, if I wished, switch and get a Ph.D. in biochemistry, but my preference was to stay with medicine. And, I believe that this is all linked to my original ambition, or desire, which was to be of some help to humankind, so to speak, in a larger sense than just on a one-to-one basis." In his last year of medical school, Salk said, "I had an opportunity to spend time in elective periods in my last year in medical school, in a laboratory that was involved in studies on influenza. The influenza virus had just been discovered about a few years before that. And, I saw the opportunity at that time to test the question as to whether we could destroy the virus infectivity and still immunize. And so, by carefully designed experiments, we found it was possible to do so." In 1941, during his postgraduate work in virology, Salk chose a two-month elective to work in the Thomas Francis ' laboratory at the University of Michigan . Francis had recently joined the faculty of the medical school after working for the Rockefeller Foundation , where he had discovered the type B influenza virus . According to Bookchin, "the two-month stint in Francis's lab was Salk's first introduction to the world of virology —and he was hooked." : 25 After graduating from medical school, Salk began his residency at New York's prestigious Mount Sinai Hospital , where he again worked in Francis's laboratory. Salk then worked at the University of Michigan School of Public Health with Francis, on an army-commissioned project in Michigan to develop an influenza vaccine. He and Francis eventually perfected a vaccine that was soon widely used at army bases, where Salk discovered and isolated one of the strains of influenza that was included in the final vaccine. : 26In 1947, Salk became ambitious for his own lab and was granted one at the University of Pittsburgh School of Medicine , but the lab was smaller than he had hoped, and he found the rules imposed by the university restrictive. In 1948, Harry Weaver, the director of research at the National Foundation for Infantile Paralysis, contacted Salk. He asked Salk to find out if there were more types of polio than the three then known and offered additional space, equipment and researchers. For the first year, he gathered supplies and researchers, including Julius Youngner , Byron Bennett, L. James Lewis, and secretary Lorraine Friedman who joined Salk's team as well. As time went on, Salk began securing grants from the Mellon family and was able to build a working virology laboratory. He later joined the National Foundation for Infantile Paralysis 's polio project established by President Franklin D. Roosevelt. Extensive publicity and fear of polio led to much increased funding, reaching $67 million by 1955. Despite the funding, research continued on live vaccines. : 85–87 Salk decided to use what he believed to be the safer 'killed' virus, instead of weakened forms of strains of polio viruses like the ones used contemporaneously by Albert Sabin , who was developing an oral vaccine. After successful tests on laboratory animals, on July 2, 1952, assisted by the staff at the D.T. Watson Home for Crippled Children, which is now the Education Center at the Watson Institute in Sewickley , Pennsylvania ), Salk injected 43 children with his killed-virus vaccine. A few weeks later, Salk injected children at the Polk State School for the Retarded and Feeble-minded. He vaccinated his own children in 1953. In 1954 he tested the vaccine on about one million children, known as the polio pioneers. The vaccine was announced as safe on April 12, 1955. The project became large, involving 100 million contributors to the March of Dimes , and 7 million volunteers. : 54 The foundation allowed itself to go into debt to finance the final research required to develop the Salk vaccine. Salk worked incessantly for two-and-a-half years. Salk's inactivated polio vaccine came into use in 1955. It is on the World Health Organization's List of Essential Medicines . Salk preferred not to have his career as a scientist affected by too much personal attention, as he had always tried to remain independent and private in his research and life, but this proved to be impossible. "Young man, a great tragedy has befallen you—you've lost your anonymity", the television personality Ed Murrow said to Salk shortly after the onslaught of media attention. When Murrow asked him, "Who owns this patent?", Salk replied, "Well, the people I would say. There is no patent. Could you patent the sun?" The vaccine is calculated to be worth $7 billion had it been patented. However, lawyers from the National Foundation for Infantile Paralysis did look into the possibility of a patent, but ultimately determined that the vaccine was not a patentable invention because of prior art . Salk served on the board of directors of the John D. and Catherine T. MacArthur Foundation . Author Jon Cohen noted, "Jonas Salk made scientists and journalists alike go goofy. As one of the only living scientists whose face was known the world over, Salk, in the public's eye, had a superstar aura. Airplane pilots would announce that he was on board, and passengers would burst into applause. Hotels routinely would upgrade him into their penthouse suites. A meal at a restaurant inevitably meant an interruption from an admirer. Scientists and journalists who regularly dealt with Salk would come to see him in more human terms, but many still initially approached him with the same drop-jawed wonder, as though some of the stardust might rub off." For the most part, however, Salk was "appalled at the demands on the public figure he has become and resentful of what he considers to be the invasion of his privacy", wrote The New York Times , a few months after his vaccine announcement. The Times article noted, "at 40, the once obscure scientist ... was lifted from his laboratory almost to the level of a folk hero." He received a presidential citation, a score of awards, four honorary degrees, half a dozen foreign decorations, and letters from thousands of fellow citizens. His alma mater, City College of New York, gave him an honorary degree as Doctor of Laws. But "despite such very nice tributes", The New York Times wrote, "Salk is profoundly disturbed by the torrent of fame that has descended upon him. ... He talks continually about getting out of the limelight and back to his laboratory ... because of his genuine distaste for publicity, which he believes is inappropriate for a scientist." During a 1980 interview, 25 years later, he said, "It's as if I've been a public property ever since, having to respond to external, as well as internal, impulses. ... It's brought me enormous gratification, opened many opportunities, but at the same time placed many burdens on me. It altered my career, my relationships with colleagues; I am a public figure, no longer one of them." "If Salk the scientist sounds austere", wrote The New York Times , "Salk the man is a person of great warmth and tremendous enthusiasm. People who meet him generally like him." A Washington newspaper correspondent commented, "He could sell me the Brooklyn Bridge, and I never bought anything before." Geneticist Walter Nelson-Rees called him "a renaissance scientist: brilliant, sophisticated, driven ... a fantastic creature." : 127 He enjoys talking to people he likes, and "he likes a lot of people", wrote the Times . "He talks quickly, articulately, and often in complete paragraphs." And "He has very little perceptible interest in the things that interest most people—such as making money." That belongs "in the category of mink coats and Cadillacs—unnecessary", he said. Salk preferred not to have his career as a scientist affected by too much personal attention, as he had always tried to remain independent and private in his research and life, but this proved to be impossible. "Young man, a great tragedy has befallen you—you've lost your anonymity", the television personality Ed Murrow said to Salk shortly after the onslaught of media attention. When Murrow asked him, "Who owns this patent?", Salk replied, "Well, the people I would say. There is no patent. Could you patent the sun?" The vaccine is calculated to be worth $7 billion had it been patented. However, lawyers from the National Foundation for Infantile Paralysis did look into the possibility of a patent, but ultimately determined that the vaccine was not a patentable invention because of prior art . Salk served on the board of directors of the John D. and Catherine T. MacArthur Foundation . Author Jon Cohen noted, "Jonas Salk made scientists and journalists alike go goofy. As one of the only living scientists whose face was known the world over, Salk, in the public's eye, had a superstar aura. Airplane pilots would announce that he was on board, and passengers would burst into applause. Hotels routinely would upgrade him into their penthouse suites. A meal at a restaurant inevitably meant an interruption from an admirer. Scientists and journalists who regularly dealt with Salk would come to see him in more human terms, but many still initially approached him with the same drop-jawed wonder, as though some of the stardust might rub off." For the most part, however, Salk was "appalled at the demands on the public figure he has become and resentful of what he considers to be the invasion of his privacy", wrote The New York Times , a few months after his vaccine announcement. The Times article noted, "at 40, the once obscure scientist ... was lifted from his laboratory almost to the level of a folk hero." He received a presidential citation, a score of awards, four honorary degrees, half a dozen foreign decorations, and letters from thousands of fellow citizens. His alma mater, City College of New York, gave him an honorary degree as Doctor of Laws. But "despite such very nice tributes", The New York Times wrote, "Salk is profoundly disturbed by the torrent of fame that has descended upon him. ... He talks continually about getting out of the limelight and back to his laboratory ... because of his genuine distaste for publicity, which he believes is inappropriate for a scientist." During a 1980 interview, 25 years later, he said, "It's as if I've been a public property ever since, having to respond to external, as well as internal, impulses. ... It's brought me enormous gratification, opened many opportunities, but at the same time placed many burdens on me. It altered my career, my relationships with colleagues; I am a public figure, no longer one of them." "If Salk the scientist sounds austere", wrote The New York Times , "Salk the man is a person of great warmth and tremendous enthusiasm. People who meet him generally like him." A Washington newspaper correspondent commented, "He could sell me the Brooklyn Bridge, and I never bought anything before." Geneticist Walter Nelson-Rees called him "a renaissance scientist: brilliant, sophisticated, driven ... a fantastic creature." : 127 He enjoys talking to people he likes, and "he likes a lot of people", wrote the Times . "He talks quickly, articulately, and often in complete paragraphs." And "He has very little perceptible interest in the things that interest most people—such as making money." That belongs "in the category of mink coats and Cadillacs—unnecessary", he said. In the years after Salk's discovery, many supporters, in particular the National Foundation, "helped him build his dream of a research complex for the investigation of biological phenomena 'from cell to society'." Called the Salk Institute for Biological Studies , it opened in 1963 in the San Diego neighborhood of La Jolla , in a purpose-built facility designed by the architect Louis Kahn . Salk believed that the institution would help new and upcoming scientists along in their careers, as he said himself, "I thought how nice it would be if a place like this existed and I was invited to work there." In 1966, Salk described his "ambitious plan for the creation of a kind of Socratic academy where the supposedly alienated two cultures of science and humanism will have a favorable atmosphere for cross-fertilization." Author and journalist Howard Taubman explained: Although he is distinctly future-oriented, Dr. Salk has not lost sight of the institute's immediate aim, which is the development and use of the new biology, called molecular and cellular biology , described as part physics, part chemistry and part biology. The broad-gauged purpose of this science is to understand man's life processes. There is talk here of the possibility, once the secret of how the cell is triggered to manufacture antibodies is discovered, that a single vaccine may be developed to protect a child against many common infectious diseases. There is speculation about the power to isolate and perhaps eliminate genetic errors that lead to birth defects. Dr. Salk, a creative man himself, hopes that the institute will do its share in probing the wisdom of nature and thus help enlarge the wisdom of man. For the ultimate purpose of science, humanism and the arts, in his judgment, is the freeing of each individual to cultivate his full creativity, in whichever direction it leads. ... As if to prepare for Socratic encounters such as these, the institute's architect, Louis Kahn, has installed blackboards in place of concrete facings on the walls along the walks. The New York Times , in a 1980 article celebrating the 25th anniversary of the Salk vaccine, described the current workings at the facility, reporting: At the institute, a magnificent complex of laboratories and study units set on a bluff overlooking the Pacific, Dr. Salk holds the titles of founding director and resident fellow. His own laboratory group is concerned with the immunologic aspects of cancer and the mechanisms of autoimmune disease, such as multiple sclerosis , in which the immune system attacks the body's own tissues. In an interview about his future hopes at the institute, he said, "In the end, what may have more significance is my creation of the institute and what will come out of it, because of its example as a place for excellence, a creative environment for creative minds." Francis Crick , co-discoverer of the structure of the DNA molecule, was a leading professor at the institute until his death in 2004. The institute also served as the basis for Bruno Latour and Steve Woolgar 's 1979 book Laboratory Life: The Construction of Scientific Facts . Beginning in the mid-1980s, Salk engaged in research to develop a vaccine for AIDS . He cofounded The Immune Response Corporation (IRC) with Kevin Kimberlin and patented Remune , an immunologic therapy , but was unable to secure liability insurance for the product. The project was discontinued in 2007, twelve years after Salk's death. [ citation needed ]In 1966, The New York Times referred to him as the "Father of Biophilosophy." According to Times journalist and author Howard Taubman , "he never forgets ... there is a vast amount of darkness for man to penetrate. As a biologist, he believes that his science is on the frontier of tremendous new discoveries; and as a philosopher, he is convinced that humanists and artists have joined the scientists to achieve an understanding of man in all his physical, mental and spiritual complexity. Such interchanges might lead, he would hope, to a new and important school of thinkers he would designate as biophilosophers." Salk told his cousin, Joel Kassiday, at a meeting of the Congressional Clearinghouse on the Future on Capitol Hill in 1984 that he was optimistic that ways to prevent most human and animal diseases would eventually be developed. Salk said people must be prepared to take prudent risks, since "a risk-free society would become a dead-end society" without progress. Salk describes his "biophilosophy" as the application of a "biological, evolutionary point of view to philosophical, cultural, social and psychological problems." He went into more detail in two of his books, Man Unfolding , and The Survival of the Wisest . In an interview in 1980, he described his thoughts on the subject, including his feeling that a sharp rise and an expected leveling off in the human population would take place and eventually bring a change in human attitudes: I think of biological knowledge as providing useful analogies for understanding human nature. ... People think of biology in terms of such practical matters as drugs, but its contribution to knowledge about living systems and ourselves will in the future be equally important. ... In the past epoch, man was concerned with death, high mortality; his attitudes were antideath, antidisease", he says. "In the future, his attitudes will be expressed in terms of prolife and prohealth. The past was dominated by death control; in the future, birth control will be more important. These changes we're observing are part of a natural order and to be expected from our capacity to adapt. It's much more important to cooperate and collaborate. We are the co-authors with nature of our destiny. His definition of a "biophilosopher" is "Someone who draws upon the scriptures of nature, recognizing that we are the product of the process of evolution, and understands that we have become the process itself, through the emergence and evolution of our consciousness, our awareness, our capacity to imagine and anticipate the future, and to choose from among alternatives." Just prior to his death, Salk was working on a new book along the theme of biophilosophy, privately reported to be titled Millennium of the Mind .The day after his graduation from medical school in 1939, Salk married Donna Lindsay, a master's candidate at the New York College of Social Work. David Oshinsky writes that Donna's father, Elmer Lindsay, "a wealthy Manhattan dentist, viewed Salk as a social inferior, several cuts below Donna's former suitors." Eventually, her father agreed to the marriage on two conditions: first, Salk must wait until he could be listed as an official M.D. on the wedding invitations, and second, he must improve his "rather pedestrian status" by giving himself a middle name." : 99 They had three children: Peter, who also became a physician and a part-time professor of infectious diseases at the University of Pittsburgh ; Darrell, who also worked with vaccines and genetics and eventually retired from the pediatrics faculty at the University of Washington School of Medicine ; and Jonathan Salk, an adult and child psychiatrist and Assistant Clinical Professor at the David Geffen School of Medicine at UCLA . In 1968, they divorced and, in 1970, Salk married French painter Françoise Gilot . Jonas Salk died from heart failure at the age of 80 on June 23, 1995, in La Jolla, and was buried at El Camino Memorial Park in San Diego.... in recognition of his 'historical medical' discovery ... Dr. Salk's achievement is meritorious service of the highest magnitude and dimension for the commonwealth, the country and mankind." The governor, who had three children, said that "as a parent he was 'humbly thankful to Dr. Salk,' and as Governor, 'proud to pay him tribute'. Because of Doctor Jonas E. Salk, our country is free from the cruel epidemics of poliomyelitis that once struck almost yearly. Because of his tireless work, untold hundreds of thousands who might have been crippled are sound in body today. These are Doctor Salk's true honors, and there is no way to add to them. This Medal of Freedom can only express our gratitude, and our deepest thanks.

Wiki

Chikungunya

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

Mosquito control

Mosquito control manages the population of mosquitoes to reduce their damage to human health, economies, and enjoyment. Mosquito control is a vital public-health practice throughout the world and especially in the tropics because mosquitoes spread many diseases, such as malaria and the Zika virus . Mosquito-control operations are targeted to multiple problems: Disease organisms transmitted by mosquitoes include West Nile virus , Saint Louis encephalitis virus , Eastern equine encephalomyelitis virus , Everglades virus , Highlands J virus , La Crosse Encephalitis virus in the United States; dengue fever , yellow fever , Ilheus virus, malaria , Zika virus and filariasis in the American tropics ; Rift Valley fever , Wuchereria bancrofti , Japanese encephalitis , chikungunya and filariasis in Africa and Asia; and Murray Valley encephalitis in Australia. Vertical transmission from adult mosquitos to larvae is possible. Depending on the situation, source reduction, biocontrol, larviciding (killing of larvae ), or adulticiding (killing of adults) may be used to manage mosquito populations. These techniques are accomplished using habitat modification, pesticide , biological-control agents, and trapping. The advantage of non-toxic methods of control is they can be used in Conservation Areas . Integrated pest management (IPM) is the use of the most environmentally appropriate method or combination of methods to control pest populations. Typical mosquito-control programs using IPM first conduct surveys, in order to determine the species composition , relative abundance and seasonal distribution of adult and larval mosquitoes, and only then is a control strategy defined.Adult mosquito populations may be monitored by landing rate counts, mechanical traps or by, lidar technology For landing rate counts, an inspector visits a set number of sites every day, counting the number of adult female mosquitoes that land on a part of the body, such as an arm or both legs, within a given time interval. Mechanical traps use a fan to blow adult mosquitoes into a collection bag that is taken back to the laboratory for analysis of catch. The mechanical traps use visual cues (light, black/white contrasts) or chemical attractants that are normally given off by mosquito hosts (e.g., carbon dioxide , ammonia , lactic acid , octenol ) to attract adult female mosquitoes. These cues are often used in combination. Entomology lidar detection has the possibility of showing the difference between male and female mosquitoes. Monitoring larval mosquito populations involves collecting larvae from standing water with a dipper or a turkey baster . The habitat, approximate total number of larvae and pupae , and species are noted for each collection. An alternative method works by providing artificial breeding spots ( ovitraps ) and collecting and counting the developing larvae at fixed intervals. Monitoring these mosquito populations is crucial to see what species are present, if mosquito numbers are rising or falling, and detecting any diseases they carry. Mosquito Alert is a cooperative citizen science project, currently run as a non-profit and coordinated by four public research centers in Spain. The aim of the project is to study, monitor, and fight the spread of invasive mosquitos. The project provided the first detection of the Asian bush mosquito Aedes japonicus in Spain in 2018, providing the first report of a population of mosquitos that were located 1,300 km from their previously nearest known location in Europe. Mechanical control is the management and control using physical means. Since many mosquitoes breed in standing water , source reduction can be as simple as emptying water from containers around the home. This is something that homeowners can accomplish. Mosquito breeding grounds can be eliminated at home by removing unused plastic pools , old tires , or buckets ; by clearing clogged gutters and repairing leaks around faucets ; by regularly (at most every 4 days) changing water in bird baths ; and by filling or draining puddles, swampy areas, and tree stumps. Eliminating such mosquito breeding areas can be an extremely effective and permanent way to reduce mosquito populations without resorting to insecticides. However, this may not be possible in parts of the developing world where water cannot be readily replaced due to irregular water supply. Many individuals also believe mosquito control is the government's responsibility, so if these methods are not done regularly by homeowners then the effectiveness is reduced. Open water marsh management (OWMM) involves the use of shallow ditches, to create a network of water flow within marshes and to connect the marsh to a pond or canal. The network of ditches drains the mosquito habitat and lets in fish which will feed on mosquito larvae. This reduces the need for other control methods such as pesticides . Simply giving the predators access to the mosquito larvae can result in long-term mosquito control. Open-water marsh management is used on both the eastern and western coasts of the United States. [ citation needed ] Rotational impoundment management (RIM) involves the use of large pumps and culverts with gates to control the water level within an impounded marsh. RIM allows mosquito control to occur while still permitting the marsh to function in a state as close to its natural condition as possible. Water is pumped into the marsh in the late spring and summer to prevent the female mosquito from laying her eggs on the soil. The marsh is allowed to drain in the fall, winter, and early spring. Gates in the culverts are used to permit fish, crustaceans, and other marsh organisms to enter and exit the marsh. RIM allows the mosquito-control goals to be met while at the same time reducing the need for pesticide use within the marsh. Rotational impoundment management is used to a great extent on the east coast of Florida. A 2019 study also explored the idea of using unmanned aerial vehicles as a valid strategy to identify and prioritize water bodies where disease vectors such as Ny . darlingi are most likely to breed. An oil drip can or oil drip barrel was a common and nontoxic anti-mosquito measure. The thin layer of oil on top of the water prevents mosquito breeding in two ways: mosquito larvae in the water cannot penetrate the oil film with their breathing tube, and so drown and die; also adult mosquitoes do not lay eggs on the oiled water. A traditional approach to controlling mosquito populations is the use of ovitraps or lethal ovitraps , which provide artificial breeding spots for mosquitoes to lay their eggs. While ovitraps only trap eggs, lethal ovitraps usually contain a chemical inside the trap that is used to kill the adult mosquito and/or the larvae in the trap. Studies have shown that with enough of these lethal ovitraps, Aedes mosquito populations can be controlled. A recent approach is the automatic lethal ovitrap, which works like a traditional ovitrap but automates all steps needed to provide the breeding spots and to destroy the developing larvae. In 2016 researchers from Laurentian University released a design for a low cost trap called an Ovillanta which consists of attractant-laced water in a section of discarded rubber tire. At regular intervals the water is run through a filter to remove any deposited eggs and larva. The water, which then contains an 'oviposition' pheromone deposited during egg-laying, is reused to attract more mosquitoes. Two studies have shown that this type of trap can attract about seven times as many mosquito eggs as a conventional ovitrap. Some newer mosquito traps or known mosquito attractants emit a plume of carbon dioxide together with other mosquito attractants such as sugary scents, lactic acid , octenol , warmth, water vapor and sounds. By mimicking a mammal's scent and outputs, the trap draws female mosquitoes toward it, where they are typically sucked into a net or holder by an electric fan where they are collected. According to the American Mosquito Control Association, the trap will kill some mosquitoes, but their effectiveness in any particular case will depend on a number of factors such as the size and species of the mosquito population and the type and location of the breeding habitat. They are useful in specimen collection studies to determine the types of mosquitoes prevalent in an area but are typically far too inefficient to be useful in reducing mosquito populations. This is a process of achieving sustainable mosquito control in an eco friendly manner by providing artificial breeding grounds with an ovitrap or an ovillanta utilizing common household utensils and destroying larvae by non-hazardous natural means such as throwing them in dry places or feeding them to larvae eating fishes like Gambusia affinis , or suffocating them by spreading a thin plastic sheet over the entire water surface to block atmospheric air. Shifting the water with larvae to another vessel and pouring a few drops of kerosene oil or insecticide/larvicide in it is another option for killing wrigglers, but not preferred due to its environmental impact . Most of the ornamental fishes eat mosquito larvae. [ citation needed ]Since many mosquitoes breed in standing water , source reduction can be as simple as emptying water from containers around the home. This is something that homeowners can accomplish. Mosquito breeding grounds can be eliminated at home by removing unused plastic pools , old tires , or buckets ; by clearing clogged gutters and repairing leaks around faucets ; by regularly (at most every 4 days) changing water in bird baths ; and by filling or draining puddles, swampy areas, and tree stumps. Eliminating such mosquito breeding areas can be an extremely effective and permanent way to reduce mosquito populations without resorting to insecticides. However, this may not be possible in parts of the developing world where water cannot be readily replaced due to irregular water supply. Many individuals also believe mosquito control is the government's responsibility, so if these methods are not done regularly by homeowners then the effectiveness is reduced. Open water marsh management (OWMM) involves the use of shallow ditches, to create a network of water flow within marshes and to connect the marsh to a pond or canal. The network of ditches drains the mosquito habitat and lets in fish which will feed on mosquito larvae. This reduces the need for other control methods such as pesticides . Simply giving the predators access to the mosquito larvae can result in long-term mosquito control. Open-water marsh management is used on both the eastern and western coasts of the United States. [ citation needed ] Rotational impoundment management (RIM) involves the use of large pumps and culverts with gates to control the water level within an impounded marsh. RIM allows mosquito control to occur while still permitting the marsh to function in a state as close to its natural condition as possible. Water is pumped into the marsh in the late spring and summer to prevent the female mosquito from laying her eggs on the soil. The marsh is allowed to drain in the fall, winter, and early spring. Gates in the culverts are used to permit fish, crustaceans, and other marsh organisms to enter and exit the marsh. RIM allows the mosquito-control goals to be met while at the same time reducing the need for pesticide use within the marsh. Rotational impoundment management is used to a great extent on the east coast of Florida. A 2019 study also explored the idea of using unmanned aerial vehicles as a valid strategy to identify and prioritize water bodies where disease vectors such as Ny . darlingi are most likely to breed. An oil drip can or oil drip barrel was a common and nontoxic anti-mosquito measure. The thin layer of oil on top of the water prevents mosquito breeding in two ways: mosquito larvae in the water cannot penetrate the oil film with their breathing tube, and so drown and die; also adult mosquitoes do not lay eggs on the oiled water. A traditional approach to controlling mosquito populations is the use of ovitraps or lethal ovitraps , which provide artificial breeding spots for mosquitoes to lay their eggs. While ovitraps only trap eggs, lethal ovitraps usually contain a chemical inside the trap that is used to kill the adult mosquito and/or the larvae in the trap. Studies have shown that with enough of these lethal ovitraps, Aedes mosquito populations can be controlled. A recent approach is the automatic lethal ovitrap, which works like a traditional ovitrap but automates all steps needed to provide the breeding spots and to destroy the developing larvae. In 2016 researchers from Laurentian University released a design for a low cost trap called an Ovillanta which consists of attractant-laced water in a section of discarded rubber tire. At regular intervals the water is run through a filter to remove any deposited eggs and larva. The water, which then contains an 'oviposition' pheromone deposited during egg-laying, is reused to attract more mosquitoes. Two studies have shown that this type of trap can attract about seven times as many mosquito eggs as a conventional ovitrap. Some newer mosquito traps or known mosquito attractants emit a plume of carbon dioxide together with other mosquito attractants such as sugary scents, lactic acid , octenol , warmth, water vapor and sounds. By mimicking a mammal's scent and outputs, the trap draws female mosquitoes toward it, where they are typically sucked into a net or holder by an electric fan where they are collected. According to the American Mosquito Control Association, the trap will kill some mosquitoes, but their effectiveness in any particular case will depend on a number of factors such as the size and species of the mosquito population and the type and location of the breeding habitat. They are useful in specimen collection studies to determine the types of mosquitoes prevalent in an area but are typically far too inefficient to be useful in reducing mosquito populations.This is a process of achieving sustainable mosquito control in an eco friendly manner by providing artificial breeding grounds with an ovitrap or an ovillanta utilizing common household utensils and destroying larvae by non-hazardous natural means such as throwing them in dry places or feeding them to larvae eating fishes like Gambusia affinis , or suffocating them by spreading a thin plastic sheet over the entire water surface to block atmospheric air. Shifting the water with larvae to another vessel and pouring a few drops of kerosene oil or insecticide/larvicide in it is another option for killing wrigglers, but not preferred due to its environmental impact . Most of the ornamental fishes eat mosquito larvae. [ citation needed ]Chemical control is the management and control using chemical means. Control of larvae can be accomplished through use of contact poisons, growth regulators, surface films, stomach poisons (including bacterial agents), and biological agents such as fungi, nematodes, copepods, and fish. A chemical commonly used in the United States is methoprene , considered slightly toxic to larger animals, which mimics and interferes with natural growth hormones in mosquito larvae, preventing development. Methoprene is frequently distributed in time-release briquette form in breeding areas. Another chemical is Temefos or temephos , a sand granular insecticide is used to treat water infected with disease carrying insects. It is believed by some researchers that the larvae of Anopheles gambiae (important vectors of malaria) can survive for several days on moist mud, and that treatments should therefore include mud and soil several meters from puddles. Control of adult mosquitoes is the most familiar aspect of mosquito control to most of the public. It is accomplished by ground-based applications or via aerial application of residual chemical insecticides such as Duet . Generally modern mosquito-control programs in developed countries use low-volume applications of insecticides, although some programs may still use thermal fogging. Beside fogging there are some other insect repellents for indoors and outdoors. An example of a synthetic insect repellent is DEET . A naturally occurring repellent is citronella . Indoor Residual Spraying ( IRS ) is another method of adulticide. Walls of properties are sprayed with an insecticide, the mosquitoes die when they land on the surface covered in insecticide. To control adult mosquitoes in India, van mounted fogging machines and hand fogging machines are used. DDT was formerly used throughout the world for large area mosquito control, but it is now banned in most developed countries. Controversially, DDT remains in common use in many developing countries (14 countries were reported to be using it in 2009 ), which claim that the public-health cost of switching to other control methods would exceed the harm caused by using DDT. It is sometimes approved for use only in specific, limited circumstances where it is most effective, such as application to walls. [ citation needed ] The role of DDT in combating mosquitoes has been the subject of considerable controversy. Although DDT has been proven to affect biodiversity and cause eggshell thinning in birds such as the bald eagle, some say that DDT is the most effective weapon in combating mosquitoes, and hence malaria. While some of this disagreement is based on differences in the extent to which disease control is valued as opposed to the value of biodiversity, [ citation needed ] there is also genuine disagreement amongst experts about the costs and benefits of using DDT. [ dubious – discuss ] Notwithstanding, DDT-resistant mosquitoes have started to increase in numbers, especially in tropics due to mutations, reducing the effectiveness of this chemical; these mutations can rapidly spread over vast areas if pesticides are applied indiscriminately (Chevillon et al. 1999). In areas where DDT resistance is encountered, malathion , propoxur or lindane is used.Control of larvae can be accomplished through use of contact poisons, growth regulators, surface films, stomach poisons (including bacterial agents), and biological agents such as fungi, nematodes, copepods, and fish. A chemical commonly used in the United States is methoprene , considered slightly toxic to larger animals, which mimics and interferes with natural growth hormones in mosquito larvae, preventing development. Methoprene is frequently distributed in time-release briquette form in breeding areas. Another chemical is Temefos or temephos , a sand granular insecticide is used to treat water infected with disease carrying insects. It is believed by some researchers that the larvae of Anopheles gambiae (important vectors of malaria) can survive for several days on moist mud, and that treatments should therefore include mud and soil several meters from puddles. Control of adult mosquitoes is the most familiar aspect of mosquito control to most of the public. It is accomplished by ground-based applications or via aerial application of residual chemical insecticides such as Duet . Generally modern mosquito-control programs in developed countries use low-volume applications of insecticides, although some programs may still use thermal fogging. Beside fogging there are some other insect repellents for indoors and outdoors. An example of a synthetic insect repellent is DEET . A naturally occurring repellent is citronella . Indoor Residual Spraying ( IRS ) is another method of adulticide. Walls of properties are sprayed with an insecticide, the mosquitoes die when they land on the surface covered in insecticide. To control adult mosquitoes in India, van mounted fogging machines and hand fogging machines are used. DDT was formerly used throughout the world for large area mosquito control, but it is now banned in most developed countries. Controversially, DDT remains in common use in many developing countries (14 countries were reported to be using it in 2009 ), which claim that the public-health cost of switching to other control methods would exceed the harm caused by using DDT. It is sometimes approved for use only in specific, limited circumstances where it is most effective, such as application to walls. [ citation needed ] The role of DDT in combating mosquitoes has been the subject of considerable controversy. Although DDT has been proven to affect biodiversity and cause eggshell thinning in birds such as the bald eagle, some say that DDT is the most effective weapon in combating mosquitoes, and hence malaria. While some of this disagreement is based on differences in the extent to which disease control is valued as opposed to the value of biodiversity, [ citation needed ] there is also genuine disagreement amongst experts about the costs and benefits of using DDT. [ dubious – discuss ] Notwithstanding, DDT-resistant mosquitoes have started to increase in numbers, especially in tropics due to mutations, reducing the effectiveness of this chemical; these mutations can rapidly spread over vast areas if pesticides are applied indiscriminately (Chevillon et al. 1999). In areas where DDT resistance is encountered, malathion , propoxur or lindane is used.Biological control is the management and control using biological means. Biological pest control , or "biocontrol", is the use of the natural enemies of pests like mosquitoes to manage the pest's populations. There are several types of biocontrol, including the direct introduction of parasites, pathogens, and predators to target mosquitoes. Effective biocontrol agents include predatory fish that feed on mosquito larvae such as mosquitofish ( Gambusia affinis ) and some cyprinids (carps and minnows) and killifish . Tilapia also consume mosquito larvae. Direct introduction of tilapia and mosquitofish into ecosystems around the world have had disastrous consequences. However, utilizing a controlled system via aquaponics provides the mosquito control without the adverse effects to the ecosystem. Other predators include dragonfly (fly) naiads , which consume mosquito larvae in the breeding waters, adult dragonflies , which eat adult mosquitoes, and some species of lizard and gecko . Biocontrol agents that have had lesser degrees of success include the predator mosquito Toxorhynchites and predator crustaceans — Mesocyclops copepods , nematodes and fungi . Predators such as birds, bats, lizards, and frogs have been used, but their effectiveness is only anecdotal. Instead of chemical insecticides, some researchers are studying biocides. Like all animals, mosquitoes are subject to disease. Invertebrate pathologists study these diseases in the hope that some of them can be utilized for mosquito management. Microbial pathogens of mosquitoes include viruses, bacteria, fungi, protozoa, nematodes and microsporidia. [ page needed ] Most notably, scientists in Burkina Faso were studying the Metarhizium fungal species. This fungus in a high concentration can slowly kill mosquitoes. To increase the lethality of the fungus, a gene from a spider was inserted into the fungus causing it to produce a neurotoxin . But it is only activated when in mosquito hemolymph. Research was done to show the fungi would not affect other insects or humans. Two other species of fungi that can kill adult mosquitoes are Metarhizium anisopliae and Beauveria bassiana . Dead spores of the soil bacterium Bacillus thuringiensis , especially Bt israelensis (BTI) interfere with dipteran larval digestive systems. It can be dispersed by hand or dropped by helicopter in large areas. BTI loses effectiveness after the larvae turn into pupae, because they stop eating. [ citation needed ] BTI was reported to be widely applied in West Africa with limited adverse effects, and may pose lesser risk than chemical pesticides. In the Wolbachia method, both male and female mosquitos that carry the Wolbachia bacterium are released into natural populations. Wolbachia boosts the natural immune response of the mosquito so that it does not easily get infected and become a host vector for mosquito-borne diseases. Therefore it is unable to easily transmit those viruses to people. This is known as replacement strategy as it aims to replace the natural population with Wolbachia -carrying ones. Since 2011, the World Mosquito Program has conducted several trials and projects, in 14 countries across Asia, Latin America and Oceania. This approach also uses Wolbachia but involves the release of only male mosquitos that carry the Wolbachia bacterium. When these male mosquitos mate with wild female mosquitos, her eggs do not hatch due to lack of biocompatibility. Wolbachia is not endemic to wild mosquito populations although it is endemic in 50% of all insect species. This is known as suppression strategy as it aims to suppress the natural reproduction cycle. Wolbachia-Aedes suppression has been piloted in various countries such as Myanmar (1967), French Polynesia (2009, 2012), USA (2014-2016, 2018), Thailand (2016), Australia (2017), Singapore (since 2016) and Puerto Rico (2020). Maui and Kuai, Hawaii - A series of IIT projects were planned to protect endangered bird species from avian malaria . The projects involve the release of large numbers of male mosquitos infected with a strain of Wolbachia that is incompatible with the strain carried by resident females. These mosquitos would not be irradiated or subject to genetic modification. Introducing large numbers of sterile males is another approach to reducing mosquito numbers. This is called Sterile Insect Technique (SIT). Radiation is used to disrupt DNA in the mosquitoes and randomly create mutations. Males with mutations that disrupt their fertility are selected and released in mass into the wild population. These sterile males mate with wild type females and no offspring is produced, reducing the population size. Guangzhou, China - A combination of SIT with IIT, were used in a mosquito control program in Guangzhou, China. The pilot trial was carried out with the support of the IAEA in cooperation with the Food and Agriculture Organization of the United Nations (FAO). The pilot demonstrated the successful near-elimination of field populations of the world's most invasive mosquito species, Aedes albopictus (Asian tiger mosquito). The two-year trial (2016–2017) covered a 32.5-hectare area on two relatively isolated islands in the Pearl River in Guangzhou. It involved the release of about 200 million irradiated mass-reared adult male mosquitoes exposed to Wolbachia bacteria. Biological pest control , or "biocontrol", is the use of the natural enemies of pests like mosquitoes to manage the pest's populations. There are several types of biocontrol, including the direct introduction of parasites, pathogens, and predators to target mosquitoes. Effective biocontrol agents include predatory fish that feed on mosquito larvae such as mosquitofish ( Gambusia affinis ) and some cyprinids (carps and minnows) and killifish . Tilapia also consume mosquito larvae. Direct introduction of tilapia and mosquitofish into ecosystems around the world have had disastrous consequences. However, utilizing a controlled system via aquaponics provides the mosquito control without the adverse effects to the ecosystem. Other predators include dragonfly (fly) naiads , which consume mosquito larvae in the breeding waters, adult dragonflies , which eat adult mosquitoes, and some species of lizard and gecko . Biocontrol agents that have had lesser degrees of success include the predator mosquito Toxorhynchites and predator crustaceans — Mesocyclops copepods , nematodes and fungi . Predators such as birds, bats, lizards, and frogs have been used, but their effectiveness is only anecdotal.Instead of chemical insecticides, some researchers are studying biocides. Like all animals, mosquitoes are subject to disease. Invertebrate pathologists study these diseases in the hope that some of them can be utilized for mosquito management. Microbial pathogens of mosquitoes include viruses, bacteria, fungi, protozoa, nematodes and microsporidia. [ page needed ] Most notably, scientists in Burkina Faso were studying the Metarhizium fungal species. This fungus in a high concentration can slowly kill mosquitoes. To increase the lethality of the fungus, a gene from a spider was inserted into the fungus causing it to produce a neurotoxin . But it is only activated when in mosquito hemolymph. Research was done to show the fungi would not affect other insects or humans. Two other species of fungi that can kill adult mosquitoes are Metarhizium anisopliae and Beauveria bassiana . Dead spores of the soil bacterium Bacillus thuringiensis , especially Bt israelensis (BTI) interfere with dipteran larval digestive systems. It can be dispersed by hand or dropped by helicopter in large areas. BTI loses effectiveness after the larvae turn into pupae, because they stop eating. [ citation needed ] BTI was reported to be widely applied in West Africa with limited adverse effects, and may pose lesser risk than chemical pesticides. In the Wolbachia method, both male and female mosquitos that carry the Wolbachia bacterium are released into natural populations. Wolbachia boosts the natural immune response of the mosquito so that it does not easily get infected and become a host vector for mosquito-borne diseases. Therefore it is unable to easily transmit those viruses to people. This is known as replacement strategy as it aims to replace the natural population with Wolbachia -carrying ones. Since 2011, the World Mosquito Program has conducted several trials and projects, in 14 countries across Asia, Latin America and Oceania.This approach also uses Wolbachia but involves the release of only male mosquitos that carry the Wolbachia bacterium. When these male mosquitos mate with wild female mosquitos, her eggs do not hatch due to lack of biocompatibility. Wolbachia is not endemic to wild mosquito populations although it is endemic in 50% of all insect species. This is known as suppression strategy as it aims to suppress the natural reproduction cycle. Wolbachia-Aedes suppression has been piloted in various countries such as Myanmar (1967), French Polynesia (2009, 2012), USA (2014-2016, 2018), Thailand (2016), Australia (2017), Singapore (since 2016) and Puerto Rico (2020). Maui and Kuai, Hawaii - A series of IIT projects were planned to protect endangered bird species from avian malaria . The projects involve the release of large numbers of male mosquitos infected with a strain of Wolbachia that is incompatible with the strain carried by resident females. These mosquitos would not be irradiated or subject to genetic modification. Maui and Kuai, Hawaii - A series of IIT projects were planned to protect endangered bird species from avian malaria . The projects involve the release of large numbers of male mosquitos infected with a strain of Wolbachia that is incompatible with the strain carried by resident females. These mosquitos would not be irradiated or subject to genetic modification. Introducing large numbers of sterile males is another approach to reducing mosquito numbers. This is called Sterile Insect Technique (SIT). Radiation is used to disrupt DNA in the mosquitoes and randomly create mutations. Males with mutations that disrupt their fertility are selected and released in mass into the wild population. These sterile males mate with wild type females and no offspring is produced, reducing the population size. Guangzhou, China - A combination of SIT with IIT, were used in a mosquito control program in Guangzhou, China. The pilot trial was carried out with the support of the IAEA in cooperation with the Food and Agriculture Organization of the United Nations (FAO). The pilot demonstrated the successful near-elimination of field populations of the world's most invasive mosquito species, Aedes albopictus (Asian tiger mosquito). The two-year trial (2016–2017) covered a 32.5-hectare area on two relatively isolated islands in the Pearl River in Guangzhou. It involved the release of about 200 million irradiated mass-reared adult male mosquitoes exposed to Wolbachia bacteria. Guangzhou, China - A combination of SIT with IIT, were used in a mosquito control program in Guangzhou, China. The pilot trial was carried out with the support of the IAEA in cooperation with the Food and Agriculture Organization of the United Nations (FAO). The pilot demonstrated the successful near-elimination of field populations of the world's most invasive mosquito species, Aedes albopictus (Asian tiger mosquito). The two-year trial (2016–2017) covered a 32.5-hectare area on two relatively isolated islands in the Pearl River in Guangzhou. It involved the release of about 200 million irradiated mass-reared adult male mosquitoes exposed to Wolbachia bacteria. These techniques share the characteristic of introducing lethal genes and reducing the size of the mosquito population over time. Another control approach under investigation for Aedes aegypti uses a strain that is genetically modified to require the antibiotic tetracycline to develop beyond the larval stage. Modified males develop normally in a nursery while they are supplied with this chemical and can be released into the wild. However, their subsequent offspring will lack tetracycline in the wild and never mature. Field trials were conducted in the Cayman Islands, Malaysia and Brazil to control the mosquitoes that cause dengue fever. In April 2014, Brazil's National Technical Commission for Biosecurity approved the commercial release of the modified mosquito. The FDA is the lead agency for regulating genetically-engineered mosquitoes in the United States. In 2014 and 2018 research was reported into other genetic methods including cytoplasmic incompatibility, chromosomal translocations, sex distortion and gene replacement. Although several years away from the field trial stage, if successful these other methods have the potential to be cheaper and to eradicate the Aedes aegypti mosquito more efficiently. A pioneering experimental demonstration of the gene drive method eradicated small populations of Anopheles gambiae . In 2020, Oxitec 's non-biting Friendly Aedes aegypti mosquito was approved for release by the US EPA and Florida state authorities. Malaysia - In several experiments, researchers released batches of male adult Aedes mosquitos with genetic modifications to study the effects of dispersal and reproduction in natural populations. Mosquito traps were ultilized for the purpose of these studies. The process allowed for the opportunity to determine which mosquitoes were affected, and provided a group to be re-released with genetic modifications resulting in the OX513A variant to reduce reproduction. Adult mosquitoes are attracted inside the traps where they died of dehydration. Research is being conducted that indicates that dismantling a protein associated with eggshell organization, factor EOF1 (factor 1), which may be unique to mosquitoes, may be a means to hamper their reproduction effectively in the wild without creating a resistant population or affecting other animals. Another control approach under investigation for Aedes aegypti uses a strain that is genetically modified to require the antibiotic tetracycline to develop beyond the larval stage. Modified males develop normally in a nursery while they are supplied with this chemical and can be released into the wild. However, their subsequent offspring will lack tetracycline in the wild and never mature. Field trials were conducted in the Cayman Islands, Malaysia and Brazil to control the mosquitoes that cause dengue fever. In April 2014, Brazil's National Technical Commission for Biosecurity approved the commercial release of the modified mosquito. The FDA is the lead agency for regulating genetically-engineered mosquitoes in the United States. In 2014 and 2018 research was reported into other genetic methods including cytoplasmic incompatibility, chromosomal translocations, sex distortion and gene replacement. Although several years away from the field trial stage, if successful these other methods have the potential to be cheaper and to eradicate the Aedes aegypti mosquito more efficiently. A pioneering experimental demonstration of the gene drive method eradicated small populations of Anopheles gambiae . In 2020, Oxitec 's non-biting Friendly Aedes aegypti mosquito was approved for release by the US EPA and Florida state authorities. Malaysia - In several experiments, researchers released batches of male adult Aedes mosquitos with genetic modifications to study the effects of dispersal and reproduction in natural populations. Mosquito traps were ultilized for the purpose of these studies. The process allowed for the opportunity to determine which mosquitoes were affected, and provided a group to be re-released with genetic modifications resulting in the OX513A variant to reduce reproduction. Adult mosquitoes are attracted inside the traps where they died of dehydration.Malaysia - In several experiments, researchers released batches of male adult Aedes mosquitos with genetic modifications to study the effects of dispersal and reproduction in natural populations. Mosquito traps were ultilized for the purpose of these studies. The process allowed for the opportunity to determine which mosquitoes were affected, and provided a group to be re-released with genetic modifications resulting in the OX513A variant to reduce reproduction. Adult mosquitoes are attracted inside the traps where they died of dehydration.Research is being conducted that indicates that dismantling a protein associated with eggshell organization, factor EOF1 (factor 1), which may be unique to mosquitoes, may be a means to hamper their reproduction effectively in the wild without creating a resistant population or affecting other animals. In Singapore , under the Control of Vectors and Pesticides Act there a legal duty on occupiers to prevent Aedes mosquitos from breeding in their homes. If breeding mosquitos are found by inspectors, occupiers are subject to a fine of 5,000 Singapore dollars or imprisonment for a term not exceeding 3 months or both. Some biologists have proposed the deliberate extinction of certain mosquito species. Biologist Olivia Judson has advocated " specicide " of thirty mosquito species by introducing a genetic element which can insert itself into another crucial gene, to create recessive " knockout genes ". She says that the Anopheles mosquitoes (which spread malaria ) and Aedes mosquitoes (which spread dengue fever , yellow fever , elephantiasis , zika , and other diseases) represent only 30 out of some 3,500 mosquito species; eradicating these would save at least one million human lives per year, at a cost of reducing the genetic diversity of the family Culicidae by 1%. She further argues that since species become extinct "all the time" the disappearance of a few more will not destroy the ecosystem : "We're not left with a wasteland every time a species vanishes. Removing one species sometimes causes shifts in the populations of other species — but different need not mean worse." In addition, anti-malarial and mosquito control programs offer little realistic hope to the 300 million people in developing nations who will be infected with acute illnesses each year. Although trials are ongoing, she writes that if they fail: "We should consider the ultimate swatting." Biologist E. O. Wilson has advocated the extinction of several species of mosquito, including malaria vector Anopheles gambiae . Wilson stated, "I'm talking about a very small number of species that have co-evolved with us and are preying on humans, so it would certainly be acceptable to remove them. I believe it's just common sense." Insect ecologist Steven Juliano has argued that "it's difficult to see what the downside would be to removal, except for collateral damage". Entomologist Joe Conlon stated that "If we eradicated them tomorrow, the ecosystems where they are active will hiccup and then get on with life. Something better or worse would take over." However, David Quammen has pointed out that mosquitoes protect forests from human exploitation and may act as competitors for other insects. In terms of malaria control, if populations of mosquitoes were temporarily reduced to zero in a region, then this would exterminate malaria, and the mosquito population could then be allowed to rebound.

Wiki

Chikungunya

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

Alphavirus

Alphavirus is a genus of RNA viruses , the sole genus in the Togaviridae family. Alphaviruses belong to group IV of the Baltimore classification of viruses , with a positive-sense, single-stranded RNA genome. There are 32 alphaviruses, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates . Alphaviruses that could infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector. Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod -borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical (although slightly pleomorphic ), and have a 40 nm isometric nucleocapsid . The alphaviruses are small, spherical, enveloped viruses with a genome of a single strand of positive-sense RNA. The total genome length ranges between 11,000 and 12,000 nucleotides, and has a 5' cap and a 3' poly-A tail . The four non-structural protein genes are encoded in the 5′ two-thirds of the genome, while the three structural proteins are translated from a subgenomic mRNA colinear with the 3′ one-third of the genome. There are two open reading frames (ORFs) in the genome, nonstructural and structural. The first is non-structural and encodes proteins (nsP1–nsP4) necessary for transcription and replication of viral RNA. The second encodes three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1, which associate as a heterodimer . The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion . The proteolytic maturation of P62 into E2 and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3, glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike. Upon exposure of the virus to the acidity of the endosome , E1 dissociates from E2 to form an E1 homotrimer , which is necessary for the fusion step to drive the cellular and viral membranes together. The alphaviral glycoprotein E1 is a class II viral fusion protein, which is structurally different from the class I fusion proteins found in influenza virus and HIV. The structure of the Semliki Forest virus revealed a structure that is similar to that of flaviviral glycoprotein E, with three structural domains in the same primary sequence arrangement. The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor . Most alphaviruses lose the peripheral protein E3, but in Semliki viruses it remains associated with the viral surface. Four nonstructural proteins (nsP1–4) which are produced as a single polyprotein constitute the virus' replication machinery. The processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. This site is located at the base of a narrow cleft and is not readily accessible. Before cleavage, nsP3 creates a ring structure that encircles nsP2. These two proteins have an extensive interface. Mutations in nsP2 that produce noncytopathic viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface region. P3 mutations opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P2/3. This in turn affects RNA infectivity altering viral RNA production levels.The proteolytic maturation of P62 into E2 and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3, glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike. Upon exposure of the virus to the acidity of the endosome , E1 dissociates from E2 to form an E1 homotrimer , which is necessary for the fusion step to drive the cellular and viral membranes together. The alphaviral glycoprotein E1 is a class II viral fusion protein, which is structurally different from the class I fusion proteins found in influenza virus and HIV. The structure of the Semliki Forest virus revealed a structure that is similar to that of flaviviral glycoprotein E, with three structural domains in the same primary sequence arrangement. The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor . Most alphaviruses lose the peripheral protein E3, but in Semliki viruses it remains associated with the viral surface.Four nonstructural proteins (nsP1–4) which are produced as a single polyprotein constitute the virus' replication machinery. The processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. This site is located at the base of a narrow cleft and is not readily accessible. Before cleavage, nsP3 creates a ring structure that encircles nsP2. These two proteins have an extensive interface. Mutations in nsP2 that produce noncytopathic viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface region. P3 mutations opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P2/3. This in turn affects RNA infectivity altering viral RNA production levels.The virus has a 60–70 nanometer diameter. It is enveloped, spherical and has a positive-strand RNA genome of ~12 kilobases. The genome encodes two polyproteins. The first polyprotein consists of four non-structural units: in order from the N terminal to the C terminal - nsP1, nsP2, nsP3, and nsP4. The second is a structural polyprotein composed of five expression units: from the N terminal to the C terminal - Capsid, E3, E2, 6K and E1. A sub genomic positive strand RNA - the 26S RNA - is replicated from a negative-stranded RNA intermediate. This serves as template for the synthesis of viral structural proteins. Most alphaviruses have conserved domains involved in regulation of viral RNA synthesis. The nucleocapsid, 40 nanometers in diameter, contains 240 copies of the capsid protein and has a T = 4 icosahedral symmetry. The E1 and E2 viral glycoproteins are embedded in the lipid bilayer. Single E1 and E2 molecules associate to form heterodimers. The E1–E2 heterodimers form one-to-one contacts between the E2 protein and the nucleocapsid monomers. The E1 and E2 proteins mediate contact between the virus and the host cell. Several receptors have been identified. These include prohibitin , phosphatidylserine , glycosaminoglycans and ATP synthase β subunit (ref needed). Replication occurs within the cytoplasm, specifically in areas termed "spherules" separated by plasma membrane invaginations from the rest. Each complex occupies one such area of about 50-nm in inner diameter. Virions mature by budding through the plasma membrane, where virus-encoded surface glycoproteins E2 and E1 are assimilated. These two glycoproteins are the targets of numerous serologic reactions and tests including neutralization and hemagglutination inhibition. The alphaviruses show various degrees of antigenic cross-reactivity in these reactions and this forms the basis for the seven antigenic complexes, 32 species and many subtypes and varieties. The E2 protein is the site of most neutralizing epitopes, while the E1 protein contains more conserved, cross-reactive epitopes.A study of this taxon suggests that this group of viruses had a marine origin—specifically the Southern Ocean—and that they have subsequently spread to both the Old and New World. There are three subgroups in this genus: the Semliki Forest virus subgroup (Semliki Forest, O'nyong-nyong and Ross River viruses); the eastern equine encephalitis virus subgroup (eastern equine encephalitis and Venezuelan equine encephalitis viruses) and the Sindbis virus subgroup. Sindbis virus, geographically restricted to the Old World, is more closely related to the eastern equine encephalitis subgroup, which are New World viruses, than it is to the Semliki Forest virus subgroup which is also found in the Old World.The following species are assigned to the genus: The seven complexes are: Barmah Forest virus is related to the Semliki Forest virus. Middelburg virus, although classified as a separate complex, may be a member of the Semliki Forest virus group. It seems likely that the genus evolved in the Old World from an insect-borne plant virus. Sindbis virus may have originated in South America. The equine encephalitis viruses and the Sindbis virus are related. The Old World and New World viruses appears to have diverged between 2000 and 3000 years ago. Divergence between the Venezuelan equine encephalitis virus and the eastern equine virus appears to have been ~1400 years ago. The fish infecting clade appears to be basal to the other species. The southern elephant seal virus appears to be related to the Sinbis clade.Barmah Forest virus is related to the Semliki Forest virus. Middelburg virus, although classified as a separate complex, may be a member of the Semliki Forest virus group. It seems likely that the genus evolved in the Old World from an insect-borne plant virus. Sindbis virus may have originated in South America. The equine encephalitis viruses and the Sindbis virus are related. The Old World and New World viruses appears to have diverged between 2000 and 3000 years ago. Divergence between the Venezuelan equine encephalitis virus and the eastern equine virus appears to have been ~1400 years ago. The fish infecting clade appears to be basal to the other species. The southern elephant seal virus appears to be related to the Sinbis clade.Fever, malaise, rash, joint pain, muscle tenderness There are many alphaviruses distributed around the world with the ability to cause human disease. Infectious arthritis , encephalitis , rashes and fever are the most commonly observed symptoms. Larger mammals such as humans and horses are usually dead-end hosts or play a minor role in viral transmission; however, in the case of Venezuelan equine encephalitis the virus is mainly amplified in horses. In most other cases the virus is maintained in nature in mosquitoes, rodents and birds. Terrestrial alphavirus infections are spread by insect vectors such as mosquitoes. Once a human is bitten by the infected mosquito, the virus can gain entry into the bloodstream, causing viremia . The alphavirus can also get into the CNS where it is able to grow and multiply within the neurones. This can lead to encephalitis , which can be fatal. When an individual is infected with this particular virus, its immune system can play a role in clearing away the virus particles. Alphaviruses are able to cause the production of interferons . Antibodies and T cells are also involved. The neutralizing antibodies also play an important role to prevent further infection and spread.Diagnoses is based on clinical samples from which the virus can be easily isolated and identified. There are no alphavirus vaccines currently available. Vector control with repellents, protective clothing, breeding site destruction, and spraying are the preventive measures of choice. [ citation needed ]Alphaviruses are of interest to gene therapy researchers, in particular the Ross River virus, Sindbis virus , Semliki Forest virus , and Venezuelan equine encephalitis virus have all been used to develop viral vectors for gene delivery. Of particular interest are the chimeric viruses that may be formed with alphaviral envelopes and retroviral capsids. Such chimeras are termed pseudotyped viruses. Alphaviral envelope pseudotypes of retroviruses or lentiviruses are able to integrate the genes that they carry into the expansive range of potential host cells that are recognized and infected by the alphaviral envelope proteins E2 and E1. The stable integration of viral genes is mediated by the retroviral interiors of these vectors. There are limitations to the use of alphaviruses in the field of gene therapy due to their lack of targeting, however, through the introduction of variable antibody domains in a non-conserved loop in the structure of E2, specific populations of cells have been targeted. Furthermore, the use of whole alphaviruses for gene therapy is of limited efficacy both because several internal alphaviral proteins are involved in the induction of apoptosis upon infection and also because the alphaviral capsid mediates only the transient introduction of mRNA into host cells. Neither of these limitations extend to alphaviral envelope pseudotypes of retroviruses or lentiviruses. However, the expression of Sindbis virus envelopes may lead to apoptosis, and their introduction into host cells upon infection by Sindbis virus envelope pseudotyped retroviruses may also lead to cell death. The toxicity of Sindbis viral envelopes may be the cause of the very low production titers realized from packaging cells constructed to produce Sindbis pseudotypes. Another branch of research involving alphaviruses is in vaccination. Alphaviruses are apt to be engineered to create replicon vectors which efficiently induce humoral and T-cell immune responses. They could therefore be used to vaccinate against viral, bacterial, protozoan, and tumor antigens.Initially, the Togaviridae family included what are now called the Flaviviruses , within the Alphavirus genus. The flaviviruses were formed into their own family when sufficient differences with the alphaviruses were noted due to the development of sequencing. Rubella virus was formerly included in the family Togaviridae in its own genus Rubivirus , but is now classified in its own family Matonaviridae . Alphavirus is now the sole genus in the family.

Wiki

Chikungunya

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

Dona Ganguly

Sanjeev Roy Swapna Roy Dona Ganguly ( née Roy ) (born 22 August 1976) is an Indian Odissi dancer. She took her dancing lessons from guru Kelucharan Mohapatra . She has a dance troupe Diksha Manjari . In 1997 she eloped with and married her childhood friend and later Indian cricketer and skipper Sourav Ganguly , 35th president of Board of Control for Cricket in India . The couple has a daughter Sana (born 2001).Dona Ganguly was born on 22 August 1976 in an affluent business family in Behala , Kolkata . Her parents were Sanjeev Roy (father) and Swapna Roy (mother). She was a student of Loreto Convent School. She eloped with her childhood friend Sourav Ganguly because their families were sworn enemies at that time. Later their families accepted the marriage and a formal wedding took place in February 1997. The couple have a daughter Sana Ganguly. On 5 October 2022, she was infected with mosquito-borne disease Chikungunya and was admitted to Woodlands Hospital, Kolkata .Dona Ganguly started learning dance from Amala Shankar when she was only 3 years old. Later she shifted to Odissi under the guidance of Guru Giridhari Nayek. Dona considers the most significant development took place when she met Kelucharan Mohapatra and started taking dancing lessons from him. At early stage of her career, in different programs, Mohapatra accompanied her many times with Pakhavaj . Dona Ganguly has a dance school named Diksha Manjari . This institution was inaugurated by Lata Mangeshkar . It has capacity of more than 2000 students. Other than dancing, this institution has other departments like Yoga , Drawing , Karate and Swimming . In October 2012, Dona Ganguly choreographed Rabindranath Tagore 's Shapmochan which she called a sombre dance drama. Dona Ganguly has a dance school named Diksha Manjari . This institution was inaugurated by Lata Mangeshkar . It has capacity of more than 2000 students. Other than dancing, this institution has other departments like Yoga , Drawing , Karate and Swimming . In October 2012, Dona Ganguly choreographed Rabindranath Tagore 's Shapmochan which she called a sombre dance drama.

Wiki

Chikungunya

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

Genital wart

Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They may be flat or project out from the surface of the skin, and their color may vary; brownish, white, pale yellow, pinkish-red, or gray. There may be a few individual warts or several, either in a cluster or merged together to look cauliflower-shaped. They can be itchy and feel burning. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection . HPV types 6 and 11 are responsible for causing majority of genital warts whereas HPV types 16, 18, 31, 33, and 35 are also occasionally found. It is spread through direct skin-to-skin contact, usually during oral , manual , vaginal , or anal sex with an infected partner. Diagnosis is generally based on symptoms and can be confirmed by biopsy . The types of HPV that cause cancer are not the same as those that cause warts. Some HPV vaccines can prevent genital warts as may condoms . Treatment options include creams such as podophyllin , imiquimod , and trichloroacetic acid . Cryotherapy or surgery may also be an option. After treatment warts often resolve within six months. Without treatment, in up to a third of cases they resolve on their own. About 1% of people in the United States have genital warts. Many people, however, are infected and do not have symptoms. Without vaccination nearly all sexually active people will get some type of HPV at one point in their lives. The disease has been known at least since the time of Hippocrates in 300 BC. They may be found anywhere in the anal or genital area, and are frequently found on external surfaces of the body, including the penile shaft , scrotum , or labia majora . They can also occur on internal surfaces like the opening to the urethra , inside the vagina , on the cervix , or in the anus . They can be as small as 1–5 mm in diameter, but can also grow or spread into large masses in the genital or anal area. In some cases they look like small stalks. They may be hard (" keratinized ") or soft. Their color can be variable, and sometimes they may bleed. In most cases, there are no symptoms of HPV infection other than the warts themselves. Sometimes warts may cause itching, redness, or discomfort, especially when they occur around the anus. Although they are usually without other physical symptoms, an outbreak of genital warts may cause psychological distress, such as anxiety , in some people. HPV is most commonly transmitted through penetrative sex . While HPV can also be transmitted via non-penetrative sexual activity, it is less transmissible than via penetrative sex. There is conflicting evidence about the effect of condoms on transmission of low-risk HPV. Some studies have suggested that they are effective at reducing transmission. Other studies suggest that condoms are not effective at preventing transmission of the low-risk HPV variants that cause genital warts. The effect of condoms on HPV transmission may also be sex-dependent; there is some evidence that condoms are more effective at preventing infection of males than of females. The types of HPV that cause warts are highly transmissible. Roughly three out of four unaffected partners of patients with warts develop them within eight months. Other studies of partner concordance suggest that the presence of visible warts may be an indicator of increased infectivity; HPV concordance rates are higher in couples where one partner has visible warts. Although 90% of HPV infections are cleared by the body within two years of infection, it is possible for infected cells to undergo a latency (quiet) period, with the first occurrence or a recurrence of symptoms happening months or years later. Latent HPV, even with no outward symptoms, is still transmissible to a sexual partner. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected. [ citation needed ] In individuals with a history of previous HPV infection, the appearance of new warts may be either from a new exposure to HPV, or from a recurrence of the previous infection. As many as one-third of people with warts will experience a recurrence. Anal or genital warts may be transmitted during birth . The presence of wart-like lesions on the genitals of young children has been suggested as an indicator of sexual abuse. However, genital warts can sometimes result from autoinoculation by warts elsewhere on the body, such as from the hands. It has also been reported from sharing of swimsuits, underwear, or bath towels, and from non-sexual touching during routine care such as diapering. Genital warts in children are less likely to be caused by HPV subtypes 6 and 11 than adults, and more likely to be caused by HPV types that cause warts elsewhere on the body ("cutaneous types"). Surveys of pediatricians who are child abuse specialists suggest that in children younger than 4 years old, there is no consensus on whether the appearance of new anal or genital warts, by itself, can be considered an indicator of sexual abuse. HPV is most commonly transmitted through penetrative sex . While HPV can also be transmitted via non-penetrative sexual activity, it is less transmissible than via penetrative sex. There is conflicting evidence about the effect of condoms on transmission of low-risk HPV. Some studies have suggested that they are effective at reducing transmission. Other studies suggest that condoms are not effective at preventing transmission of the low-risk HPV variants that cause genital warts. The effect of condoms on HPV transmission may also be sex-dependent; there is some evidence that condoms are more effective at preventing infection of males than of females. The types of HPV that cause warts are highly transmissible. Roughly three out of four unaffected partners of patients with warts develop them within eight months. Other studies of partner concordance suggest that the presence of visible warts may be an indicator of increased infectivity; HPV concordance rates are higher in couples where one partner has visible warts. Although 90% of HPV infections are cleared by the body within two years of infection, it is possible for infected cells to undergo a latency (quiet) period, with the first occurrence or a recurrence of symptoms happening months or years later. Latent HPV, even with no outward symptoms, is still transmissible to a sexual partner. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected. [ citation needed ] In individuals with a history of previous HPV infection, the appearance of new warts may be either from a new exposure to HPV, or from a recurrence of the previous infection. As many as one-third of people with warts will experience a recurrence. Anal or genital warts may be transmitted during birth . The presence of wart-like lesions on the genitals of young children has been suggested as an indicator of sexual abuse. However, genital warts can sometimes result from autoinoculation by warts elsewhere on the body, such as from the hands. It has also been reported from sharing of swimsuits, underwear, or bath towels, and from non-sexual touching during routine care such as diapering. Genital warts in children are less likely to be caused by HPV subtypes 6 and 11 than adults, and more likely to be caused by HPV types that cause warts elsewhere on the body ("cutaneous types"). Surveys of pediatricians who are child abuse specialists suggest that in children younger than 4 years old, there is no consensus on whether the appearance of new anal or genital warts, by itself, can be considered an indicator of sexual abuse. The diagnosis of genital warts is most often made visually, but may require confirmation by biopsy in some cases. Smaller warts may occasionally be confused with molluscum contagiosum . Genital warts, histopathologically , characteristically rise above the skin surface due to enlargement of the dermal papillae , have parakeratosis and the characteristic nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing). DNA tests are available for diagnosis of high-risk HPV infections. Because genital warts are caused by low-risk HPV types, DNA tests cannot be used for diagnosis of genital warts or other low-risk HPV infections. Some practitioners use an acetic acid solution to identify smaller warts ("subclinical lesions"), but this practice is controversial. Because a diagnosis made with acetic acid will not meaningfully affect the course of the disease, and cannot be verified by a more specific test, a 2007 UK guideline advises against its use. Gardasil (sold by Merck & Co. ) is a vaccine that protects against human papillomavirus types 6, 11, 16 and 18. Types 6 and 11 cause genital warts, while 16 and 18 cause cervical cancer . The vaccine is preventive, not therapeutic, and must be given before exposure to the virus type to be effective, ideally before the beginning of sexual activity. The vaccine is approved by the US Food and Drug Administration for use in both males and females as early as 9 years of age. In the UK, Gardasil replaced Cervarix in September 2012 for reasons unrelated to safety. Cervarix had been used routinely in young females from its introduction in 2008, but was only effective against the high-risk HPV types 16 and 18, neither of which typically causes warts. [ citation needed ]There is no cure for HPV. Existing treatments are directed towards the removal of visible warts, but these may also regress on their own without any therapy. There is no evidence to suggest that removing visible warts reduces transmission of the underlying HPV infection. As many as 80% of people with HPV will clear the infection within 18 months. A healthcare practitioner may offer one of several ways to treat warts, depending on their number, sizes, locations, or other factors. All treatments can cause depigmentation, itching, pain, or scarring . Treatments can be classified as either physically ablative , or topical agents. Physically ablative therapies are considered more effective at initial wart removal, but like all therapies have significant recurrence rates. Many therapies, including folk remedies , have been suggested for treating genital warts, some of which have little evidence to suggest they are effective or safe. Those listed here are ones mentioned in national or international practice guidelines as having some basis in evidence for their use. [ citation needed ] Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts. Podophyllin, podofilox and isotretinoin should not be used during pregnancy , as they could cause birth defects in the fetus . Isotretinoin taken orally has been shown to treat recalcitrant condylomata acuminata (RCA) of the cervix.Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts. Podophyllin, podofilox and isotretinoin should not be used during pregnancy , as they could cause birth defects in the fetus .Podophyllin, podofilox and isotretinoin should not be used during pregnancy , as they could cause birth defects in the fetus .Isotretinoin taken orally has been shown to treat recalcitrant condylomata acuminata (RCA) of the cervix.Genital HPV infections have an estimated prevalence in the US of 10–20% and clinical manifestations in 1% of the sexually active adult population. US incidence of HPV infection has increased between 1975 and 2006. About 80% of those infected are between the ages of 17–33. Although treatments can remove warts, they do not remove the HPV, so warts can recur after treatment (about 50–73% of the time ). Warts can also spontaneously regress (with or without treatment). Traditional theories postulated that the virus remained in the body for a lifetime. However, studies using sensitive DNA techniques have shown that through immunological response , the virus can either be cleared or suppressed to levels below what polymerase chain reaction (PCR) tests can measure. One study testing genital skin for subclinical HPV using PCR found a prevalence of 10%. A condyloma acuminatum is a single genital wart, and condylomata acuminata are multiple genital warts. The word roots mean 'pointed wart' (from Greek ÎºÏŒÎ½Î´Ï Î»Î¿Ï‚ 'knuckle', Greek -ωμα -oma 'disease', and Latin acuminatum 'pointed'). Although similarly named, it is not the same as condyloma latum , which is a complication of secondary syphilis . [ citation needed ]

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/SARS-CoV-2/html

SARS-CoV-2

2019-nCoV Severe acute respiratory syndrome coronavirus 2 ( SARS‑CoV‑2 ) is a strain of coronavirus that causes COVID-19 , the respiratory illness responsible for the COVID-19 pandemic . The virus previously had the provisional name 2019 novel coronavirus ( 2019-nCoV ), and has also been called human coronavirus 2019 ( HCoV-19 or hCoV-19 ). First identified in the city of Wuhan , Hubei, China, the World Health Organization designated the outbreak a public health emergency of international concern from January 30, 2020, to May 5, 2023. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans. SARS‑CoV‑2 is a strain of the species severe-acute-respiratory-syndrome-related coronavirus (SARSr-CoV), as is SARS-CoV-1 , the virus that caused the 2002–2004 SARS outbreak . There are animal-borne coronavirus strains more closely related to SARS-CoV-2, the most closely known relative being the BANAL-52 bat coronavirus. SARS-CoV-2 is of zoonotic origin; its close genetic similarity to bat coronaviruses suggests it emerged from such a bat-borne virus . Research is ongoing as to whether SARS‑CoV‑2 came directly from bats or indirectly through any intermediate hosts. The virus shows little genetic diversity , indicating that the spillover event introducing SARS‑CoV‑2 to humans is likely to have occurred in late 2019. Epidemiological studies estimate that in the period between December 2019 and September 2020 each infection resulted in an average of 2.4–3.4 new infections when no members of the community were immune and no preventive measures were taken. However, some subsequent variants have become more infectious. The virus is airborne and primarily spreads between people through close contact and via aerosols and respiratory droplets that are exhaled when talking, breathing, or otherwise exhaling, as well as those produced from coughs and sneezes. It enters human cells by binding to angiotensin-converting enzyme 2 (ACE2), a membrane protein that regulates the renin–angiotensin system. During the initial outbreak in Wuhan , China, various names were used for the virus; some names used by different sources included "the coronavirus" or "Wuhan coronavirus". In January 2020, the World Health Organization (WHO) recommended "2019 novel coronavirus" (2019-nCoV) as the provisional name for the virus. This was in accordance with WHO's 2015 guidance against using geographical locations, animal species, or groups of people in disease and virus names. On 11 February 2020, the International Committee on Taxonomy of Viruses adopted the official name "severe acute respiratory syndrome coronavirus 2" (SARS‑CoV‑2). To avoid confusion with the disease SARS , the WHO sometimes refers to SARS‑CoV‑2 as "the COVID-19 virus" in public health communications and the name HCoV-19 was included in some research articles. Referring to COVID-19 as the "Wuhan virus" has been described as dangerous by WHO officials, and as xenophobic by many journalists and academics. Human-to-human transmission of SARS‑CoV‑2 was confirmed on 20 January 2020 during the COVID-19 pandemic . Transmission was initially assumed to occur primarily via respiratory droplets from coughs and sneezes within a range of about 1.8 metres (6 ft) . Laser light scattering experiments suggest that speaking is an additional mode of transmission and a far-reaching one, indoors, with little air flow. Other studies have suggested that the virus may be airborne as well, with aerosols potentially being able to transmit the virus. During human-to-human transmission, between 200 and 800 infectious SARS‑CoV‑2 virions are thought to initiate a new infection. If confirmed, aerosol transmission has biosafety implications because a major concern associated with the risk of working with emerging viruses in the laboratory is the generation of aerosols from various laboratory activities which are not immediately recognizable and may affect other scientific personnel. Indirect contact via contaminated surfaces is another possible cause of infection. Preliminary research indicates that the virus may remain viable on plastic ( polypropylene ) and stainless steel ( AISI 304 ) for up to three days, but it does not survive on cardboard for more than one day or on copper for more than four hours. The virus is inactivated by soap, which destabilizes its lipid bilayer . Viral RNA has also been found in stool samples and semen from infected individuals. The degree to which the virus is infectious during the incubation period is uncertain, but research has indicated that the pharynx reaches peak viral load approximately four days after infection or in the first week of symptoms and declines thereafter. The duration of SARS-CoV-2 RNA shedding is generally between 3 and 46 days after symptom onset. A study by a team of researchers from the University of North Carolina found that the nasal cavity is seemingly the dominant initial site of infection, with subsequent aspiration -mediated virus-seeding into the lungs in SARS‑CoV‑2 pathogenesis. They found that there was an infection gradient from high in proximal towards low in distal pulmonary epithelial cultures, with a focal infection in ciliated cells and type 2 pneumocytes in the airway and alveolar regions respectively. Studies have identified a range of animals—such as cats, ferrets, hamsters, non-human primates, minks, tree shrews, raccoon dogs, fruit bats, and rabbits—that are susceptible and permissive to SARS-CoV-2 infection. Some institutions have advised that those infected with SARS‑CoV‑2 restrict their contact with animals. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". One meta-analysis found that 17% of infections are asymptomatic, and asymptomatic individuals were 42% less likely to transmit the virus. However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections. That may explain how out of 217 on board a cruise liner that docked at Montevideo , only 24 of 128 who tested positive for viral RNA showed symptoms. Similarly, a study of ninety-four patients hospitalized in January and February 2020 estimated patients began shedding virus two to three days before symptoms appear and that "a substantial proportion of transmission probably occurred before first symptoms in the index case ". The authors later published a correction that showed that shedding began earlier than first estimated, four to five days before symptoms appear. There is uncertainty about reinfection and long-term immunity. It is not known how common reinfection is, but reports have indicated that it is occurring with variable severity. The first reported case of reinfection was a 33-year-old man from Hong Kong who first tested positive on 26 March 2020, was discharged on 15 April 2020 after two negative tests, and tested positive again on 15 August 2020 (142 days later), which was confirmed by whole-genome sequencing showing that the viral genomes between the episodes belong to different clades . The findings had the implications that herd immunity may not eliminate the virus if reinfection is not an uncommon occurrence and that vaccines may not be able to provide lifelong protection against the virus. Another case study described a 25-year-old man from Nevada who tested positive for SARS‑CoV‑2 on 18 April 2020 and on 5 June 2020 (separated by two negative tests). Since genomic analyses showed significant genetic differences between the SARS‑CoV‑2 variant sampled on those two dates, the case study authors determined this was a reinfection. The man's second infection was symptomatically more severe than the first infection, but the mechanisms that could account for this are not known. On 1 February 2020, the World Health Organization (WHO) indicated that "transmission from asymptomatic cases is likely not a major driver of transmission". One meta-analysis found that 17% of infections are asymptomatic, and asymptomatic individuals were 42% less likely to transmit the virus. However, an epidemiological model of the beginning of the outbreak in China suggested that "pre-symptomatic shedding may be typical among documented infections" and that subclinical infections may have been the source of a majority of infections. That may explain how out of 217 on board a cruise liner that docked at Montevideo , only 24 of 128 who tested positive for viral RNA showed symptoms. Similarly, a study of ninety-four patients hospitalized in January and February 2020 estimated patients began shedding virus two to three days before symptoms appear and that "a substantial proportion of transmission probably occurred before first symptoms in the index case ". The authors later published a correction that showed that shedding began earlier than first estimated, four to five days before symptoms appear. There is uncertainty about reinfection and long-term immunity. It is not known how common reinfection is, but reports have indicated that it is occurring with variable severity. The first reported case of reinfection was a 33-year-old man from Hong Kong who first tested positive on 26 March 2020, was discharged on 15 April 2020 after two negative tests, and tested positive again on 15 August 2020 (142 days later), which was confirmed by whole-genome sequencing showing that the viral genomes between the episodes belong to different clades . The findings had the implications that herd immunity may not eliminate the virus if reinfection is not an uncommon occurrence and that vaccines may not be able to provide lifelong protection against the virus. Another case study described a 25-year-old man from Nevada who tested positive for SARS‑CoV‑2 on 18 April 2020 and on 5 June 2020 (separated by two negative tests). Since genomic analyses showed significant genetic differences between the SARS‑CoV‑2 variant sampled on those two dates, the case study authors determined this was a reinfection. The man's second infection was symptomatically more severe than the first infection, but the mechanisms that could account for this are not known. No natural reservoir for SARS-CoV-2 has been identified. Prior to the emergence of SARS-CoV-2 as a pathogen infecting humans, there had been two previous zoonosis -based coronavirus epidemics, those caused by SARS-CoV-1 and MERS-CoV . The first known infections from SARS‑CoV‑2 were discovered in Wuhan, China. The original source of viral transmission to humans remains unclear, as does whether the virus became pathogenic before or after the spillover event . Because many of the early infectees were workers at the Huanan Seafood Market , it has been suggested that the virus might have originated from the market. However, other research indicates that visitors may have introduced the virus to the market, which then facilitated rapid expansion of the infections. A March 2021 WHO-convened report stated that human spillover via an intermediate animal host was the most likely explanation, with direct spillover from bats next most likely. Introduction through the food supply chain and the Huanan Seafood Market was considered another possible, but less likely, explanation. An analysis in November 2021, however, said that the earliest-known case had been misidentified and that the preponderance of early cases linked to the Huanan Market argued for it being the source. For a virus recently acquired through a cross-species transmission, rapid evolution is expected. The mutation rate estimated from early cases of SARS-CoV-2 was of 6.54 × 10 −4 per site per year. Coronaviruses in general have high genetic plasticity , but SARS-CoV-2's viral evolution is slowed by the RNA proofreading capability of its replication machinery. For comparison, the viral mutation rate in vivo of SARS-CoV-2 has been found to be lower than that of influenza. Research into the natural reservoir of the virus that caused the 2002–2004 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses , most originating in horseshoe bats . The closest match by far, published in Nature (journal) in February 2022, were viruses BANAL-52 (96.8% resemblance to SARS‑CoV‑2), BANAL-103 and BANAL-236, collected in three different species of bats in Feuang , Laos. An earlier source published in February 2020 identified the virus RaTG13 , collected in bats in Mojiang , Yunnan, China to be the closest to SARS‑CoV‑2, with 96.1% resemblance. None of the above are its direct ancestor. Bats are considered the most likely natural reservoir of SARS‑CoV‑2. Differences between the bat coronavirus and SARS‑CoV‑2 suggest that humans may have been infected via an intermediate host; although the source of introduction into humans remains unknown. Although the role of pangolins as an intermediate host was initially posited (a study published in July 2020 suggested that pangolins are an intermediate host of SARS‑CoV‑2-like coronaviruses ), subsequent studies have not substantiated their contribution to the spillover. Evidence against this hypothesis includes the fact that pangolin virus samples are too distant to SARS-CoV-2: isolates obtained from pangolins seized in Guangdong were only 92% identical in sequence to the SARS‑CoV‑2 genome (matches above 90 percent may sound high, but in genomic terms it is a wide evolutionary gap ). In addition, despite similarities in a few critical amino acids, pangolin virus samples exhibit poor binding to the human ACE2 receptor. 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 . Like the SARS-related coronavirus implicated in the 2003 SARS outbreak, SARS‑CoV‑2 is a member of the subgenus Sarbecovirus ( beta-CoV lineage B). Coronaviruses undergo frequent recombination. The mechanism of recombination in unsegmented RNA viruses such as SARS-CoV-2 is generally by copy-choice replication, in which gene material switches from one RNA template molecule to another during replication. The SARS-CoV-2 RNA sequence is approximately 30,000 bases in length, relatively long for a coronavirus—which in turn carry the largest genomes among all RNA families. Its genome consists nearly entirely of protein-coding sequences, a trait shared with other coronaviruses. A distinguishing feature of SARS‑CoV‑2 is its incorporation of a polybasic site cleaved by furin , which appears to be an important element enhancing its virulence. It was suggested that the acquisition of the furin-cleavage site in the SARS-CoV-2 S protein was essential for zoonotic transfer to humans. The furin protease recognizes the canonical peptide sequence R X[ R / K ] R ↓X where the cleavage site is indicated by a down arrow and X is any amino acid . In SARS-CoV-2 the recognition site is formed by the incorporated 12 codon nucleotide sequence CCT CGG CGG GCA which corresponds to the amino acid sequence P RR A . This sequence is upstream of an arginine and serine which forms the S1/S2 cleavage site ( P RR A R ↓ S ) of the spike protein. Although such sites are a common naturally-occurring feature of other viruses within the Subfamily Orthocoronavirinae, it appears in few other viruses from the Beta-CoV genus, and it is unique among members of its subgenus for such a site. The furin cleavage site PRRAR↓ is highly similar to that of the feline coronavirus , an alphacoronavirus 1 strain. Viral genetic sequence data can provide critical information about whether viruses separated by time and space are likely to be epidemiologically linked. With a sufficient number of sequenced genomes , it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS‑CoV‑2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions; the number of genomes increased to 42 by 30 January 2020. A phylogenetic analysis of those samples showed they were "highly related with at most seven mutations relative to a common ancestor ", implying that the first human infection occurred in November or December 2019. Examination of the topology of the phylogenetic tree at the start of the pandemic also found high similarities between human isolates. As of 21 August 2021 , [ update ] 3,422 SARS‑CoV‑2 genomes, belonging to 19 strains, sampled on all continents except Antarctica were publicly available. On 11 February 2020, the International Committee on Taxonomy of Viruses announced that according to existing rules that compute hierarchical relationships among coronaviruses based on five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus from the 2003 SARS outbreak were insufficient to make them separate viral species . Therefore, they identified 2019-nCoV as a virus of Severe acute respiratory syndrome–related coronavirus . In July 2020, scientists reported that a more infectious SARS‑CoV‑2 variant with spike protein variant G614 has replaced D614 as the dominant form in the pandemic. Coronavirus genomes and subgenomes encode six open reading frames (ORFs). In October 2020, researchers discovered a possible overlapping gene named ORF3d , in the SARS‑CoV‑2 genome . It is unknown if the protein produced by ORF3d has any function, but it provokes a strong immune response. ORF3d has been identified before, in a variant of coronavirus that infects pangolins . A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is: ( Bat ) Rc-o319 , 81% to SARS-CoV-2, Rhinolophus cornutus , Iwate , Japan Bat SL-ZXC21 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan , Zhejiang Bat SL-ZC45 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan, Zhejiang Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng , Cambodia Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng, Cambodia (Bat) RacCS203 , 91.5% to SARS-CoV-2, Rhinolophus acuminatus , Chachoengsao , Thailand (Bat) RmYN02 , 93.3% to SARS-CoV-2, Rhinolophus malayanus , Mengla , Yunnan (Bat) RpYN06 , 94.4% to SARS-CoV-2, Rhinolophus pusillus , Xishuangbanna , Yunnan (Bat) RaTG13 , 96.1% to SARS-CoV-2, Rhinolophus affinis , Mojiang , Yunnan (Bat) BANAL-52 , 96.8% to SARS-CoV-2, Rhinolophus malayanus , Vientiane , Laos SARS-CoV-2 SARS-CoV-1 , 79% to SARS-CoV-2 There are many thousands of variants of SARS-CoV-2, which can be grouped into the much larger clades . Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR). Several notable variants of SARS-CoV-2 emerged in late 2020. The World Health Organization has currently declared five variants of concern , which are as follows: Other notable variants include 6 other WHO-designated variants under investigation and Cluster 5 , which emerged among mink in Denmark and resulted in a mink euthanasia campaign rendering it virtually extinct. A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is: ( Bat ) Rc-o319 , 81% to SARS-CoV-2, Rhinolophus cornutus , Iwate , Japan Bat SL-ZXC21 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan , Zhejiang Bat SL-ZC45 , 88% to SARS-CoV-2, Rhinolophus pusillus , Zhoushan, Zhejiang Pangolin SARSr-CoV-GX, 85.3% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Pangolin SARSr-CoV-GD, 90.1% to SARS-CoV-2, Manis javanica , smuggled from Southeast Asia Bat RshSTT182, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng , Cambodia Bat RshSTT200, 92.6% to SARS-CoV-2, Rhinolophus shameli , Steung Treng, Cambodia (Bat) RacCS203 , 91.5% to SARS-CoV-2, Rhinolophus acuminatus , Chachoengsao , Thailand (Bat) RmYN02 , 93.3% to SARS-CoV-2, Rhinolophus malayanus , Mengla , Yunnan (Bat) RpYN06 , 94.4% to SARS-CoV-2, Rhinolophus pusillus , Xishuangbanna , Yunnan (Bat) RaTG13 , 96.1% to SARS-CoV-2, Rhinolophus affinis , Mojiang , Yunnan (Bat) BANAL-52 , 96.8% to SARS-CoV-2, Rhinolophus malayanus , Vientiane , Laos SARS-CoV-2 SARS-CoV-1 , 79% to SARS-CoV-2 There are many thousands of variants of SARS-CoV-2, which can be grouped into the much larger clades . Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR). Several notable variants of SARS-CoV-2 emerged in late 2020. The World Health Organization has currently declared five variants of concern , which are as follows: Other notable variants include 6 other WHO-designated variants under investigation and Cluster 5 , which emerged among mink in Denmark and resulted in a mink euthanasia campaign rendering it virtually extinct. There are many thousands of variants of SARS-CoV-2, which can be grouped into the much larger clades . Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR). Several notable variants of SARS-CoV-2 emerged in late 2020. The World Health Organization has currently declared five variants of concern , which are as follows: Other notable variants include 6 other WHO-designated variants under investigation and Cluster 5 , which emerged among mink in Denmark and resulted in a mink euthanasia campaign rendering it virtually extinct. Each SARS-CoV-2 virion is 60–140 nanometres (2.4 × 10 −6 –5.5 × 10 −6 in) in diameter; its mass within the global human populace has been estimated as being between 0.1 and 10 kilograms. Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S ( spike ), E ( envelope ), M ( membrane ), and N ( nucleocapsid ) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope . Coronavirus S proteins are glycoproteins and also type I membrane proteins (membranes containing a single transmembrane domain oriented on the extracellular side). They are divided into two functional parts (S1 and S2). In SARS-CoV-2, the spike protein, which has been imaged at the atomic level using cryogenic electron microscopy , is the protein responsible for allowing the virus to attach to and fuse with the membrane of a host cell; specifically, its S1 subunit catalyzes attachment, the S2 subunit fusion. As of early 2022, about 7 million SARS-CoV-2 genomes had been sequenced and deposited into public databases and another 800,000 or so were added each month. By September 2023, the GISAID EpiCoV database contained more than 16 million genome sequences. SARS-CoV-2 has a linear, positive-sense , single-stranded RNA genome about 30,000 bases long. Its genome has a bias against cytosine (C) and guanine (G) nucleotides , like other coronaviruses. The genome has the highest composition of U (32.2%), followed by A (29.9%), and a similar composition of G (19.6%) and C (18.3%). The nucleotide bias arises from the mutation of guanines and cytosines to adenosines and uracils , respectively. The mutation of CG dinucleotides is thought to arise to avoid the zinc finger antiviral protein related defense mechanism of cells, and to lower the energy to unbind the genome during replication and translation (adenosine and uracil base pair via two hydrogen bonds , cytosine and guanine via three). The depletion of CG dinucleotides in its genome has led the virus to have a noticeable codon usage bias . For instance, arginine's six different codons have a relative synonymous codon usage of AGA (2.67), CGU (1.46), AGG (.81), CGC (.58), CGA (.29), and CGG (.19). A similar codon usage bias trend is seen in other SARS–related coronaviruses. Virus infections start when viral particles bind to host surface cellular receptors. Protein modeling experiments on the spike protein of the virus soon suggested that SARS‑CoV‑2 has sufficient affinity to the receptor angiotensin converting enzyme 2 (ACE2) on human cells to use them as a mechanism of cell entry . By 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS‑CoV‑2. Studies have shown that SARS‑CoV‑2 has a higher affinity to human ACE2 than the original SARS virus. SARS‑CoV‑2 may also use basigin to assist in cell entry. Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS‑CoV‑2. The host protein neuropilin 1 (NRP1) may aid the virus in host cell entry using ACE2. After a SARS‑CoV‑2 virion attaches to a target cell, the cell's TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide in the S2 subunit, and the host receptor ACE2. After fusion, an endosome forms around the virion, separating it from the rest of the host cell. The virion escapes when the pH of the endosome drops or when cathepsin , a host cysteine protease, cleaves it. The virion then releases RNA into the cell and forces the cell to produce and disseminate copies of the virus , which infect more cells. SARS‑CoV‑2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response . Whether they include downregulation of ACE2, as seen in similar coronaviruses, remains under investigation (as of May 2020). Each SARS-CoV-2 virion is 60–140 nanometres (2.4 × 10 −6 –5.5 × 10 −6 in) in diameter; its mass within the global human populace has been estimated as being between 0.1 and 10 kilograms. Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S ( spike ), E ( envelope ), M ( membrane ), and N ( nucleocapsid ) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope . Coronavirus S proteins are glycoproteins and also type I membrane proteins (membranes containing a single transmembrane domain oriented on the extracellular side). They are divided into two functional parts (S1 and S2). In SARS-CoV-2, the spike protein, which has been imaged at the atomic level using cryogenic electron microscopy , is the protein responsible for allowing the virus to attach to and fuse with the membrane of a host cell; specifically, its S1 subunit catalyzes attachment, the S2 subunit fusion. As of early 2022, about 7 million SARS-CoV-2 genomes had been sequenced and deposited into public databases and another 800,000 or so were added each month. By September 2023, the GISAID EpiCoV database contained more than 16 million genome sequences. SARS-CoV-2 has a linear, positive-sense , single-stranded RNA genome about 30,000 bases long. Its genome has a bias against cytosine (C) and guanine (G) nucleotides , like other coronaviruses. The genome has the highest composition of U (32.2%), followed by A (29.9%), and a similar composition of G (19.6%) and C (18.3%). The nucleotide bias arises from the mutation of guanines and cytosines to adenosines and uracils , respectively. The mutation of CG dinucleotides is thought to arise to avoid the zinc finger antiviral protein related defense mechanism of cells, and to lower the energy to unbind the genome during replication and translation (adenosine and uracil base pair via two hydrogen bonds , cytosine and guanine via three). The depletion of CG dinucleotides in its genome has led the virus to have a noticeable codon usage bias . For instance, arginine's six different codons have a relative synonymous codon usage of AGA (2.67), CGU (1.46), AGG (.81), CGC (.58), CGA (.29), and CGG (.19). A similar codon usage bias trend is seen in other SARS–related coronaviruses. Virus infections start when viral particles bind to host surface cellular receptors. Protein modeling experiments on the spike protein of the virus soon suggested that SARS‑CoV‑2 has sufficient affinity to the receptor angiotensin converting enzyme 2 (ACE2) on human cells to use them as a mechanism of cell entry . By 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS‑CoV‑2. Studies have shown that SARS‑CoV‑2 has a higher affinity to human ACE2 than the original SARS virus. SARS‑CoV‑2 may also use basigin to assist in cell entry. Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS‑CoV‑2. The host protein neuropilin 1 (NRP1) may aid the virus in host cell entry using ACE2. After a SARS‑CoV‑2 virion attaches to a target cell, the cell's TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide in the S2 subunit, and the host receptor ACE2. After fusion, an endosome forms around the virion, separating it from the rest of the host cell. The virion escapes when the pH of the endosome drops or when cathepsin , a host cysteine protease, cleaves it. The virion then releases RNA into the cell and forces the cell to produce and disseminate copies of the virus , which infect more cells. SARS‑CoV‑2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response . Whether they include downregulation of ACE2, as seen in similar coronaviruses, remains under investigation (as of May 2020). Very few drugs are known to effectively inhibit SARS‑CoV‑2. Masitinib is a clinically safe drug and was recently found to inhibit its main protease , 3CLpro and showed >200-fold reduction in viral titers in the lungs and nose in mice. However, it is not approved for the treatment of COVID-19 in humans as of August 2021. [ needs update ] In December 2021, the United States granted emergency use authorization to Nirmatrelvir/ritonavir for the treatment of the virus; the European Union , United Kingdom , and Canada followed suit with full authorization soon after. One study found that Nirmatrelvir/ritonavir reduced the risk of hospitalization and death by 88%. COVID Moonshot is an international collaborative open-science project started in March 2020 with the goal of developing an un- patented oral antiviral drug for treatment of SARS-CoV-2. Retrospective tests collected within the Chinese surveillance system revealed no clear indication of substantial unrecognized circulation of SARS‑CoV‑2 in Wuhan during the latter part of 2019. A meta-analysis from November 2020 estimated the basic reproduction number ( R 0 {\displaystyle R_{0}} ) of the virus to be between 2.39 and 3.44. This means each infection from the virus is expected to result in 2.39 to 3.44 new infections when no members of the community are immune and no preventive measures are taken. The reproduction number may be higher in densely populated conditions such as those found on cruise ships . Human behavior affects the R0 value and hence estimates of R0 differ between different countries, cultures, and social norms. For instance, one study found relatively low R0 (~3.5) in Sweden, Belgium and the Netherlands, while Spain and the US had significantly higher R0 values (5.9 to 6.4, respectively). There have been about 96,000 confirmed cases of infection in mainland China. While the proportion of infections that result in confirmed cases or progress to diagnosable disease remains unclear, one mathematical model estimated that 75,815 people were infected on 25 January 2020 in Wuhan alone, at a time when the number of confirmed cases worldwide was only 2,015. Before 24 February 2020, over 95% of all deaths from COVID-19 worldwide had occurred in Hubei province , where Wuhan is located. As of 10 March 2023 , the percentage had decreased to 0.047% . As of 10 March 2023 , there were 676,609,955 total confirmed cases of SARS‑CoV‑2 infection. The total number of deaths attributed to the virus was 6,881,955 .

Wiki

Chikungunya

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

MMR vaccine and autism

Claims of a link between the MMR vaccine and autism have been extensively investigated and found to be false. The link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud , characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper, authored by discredited former doctor Andrew Wakefield and published in The Lancet , falsely claimed the vaccine was linked to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccine activists . The claims in the paper were widely reported, leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continues in anti-vaccination propaganda despite being refuted, has led to an increase in the incidence of measles and mumps , resulting in deaths and serious permanent injuries. Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention , the American Academy of Pediatrics , the Institute of Medicine of the US National Academy of Sciences , the UK National Health Service , and the Cochrane Library all found no link between the MMR vaccine and autism. Physicians, medical journals, and editors have described Wakefield's actions as fraudulent and tied them to epidemics and deaths. An investigation by journalist Brian Deer found that Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest , had manipulated evidence, and had broken other ethical codes. [ which? ] The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet ' s editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010 and was struck off the Medical Register , meaning he could no longer practise as a physician in the UK. In January 2011, Deer published a series of reports in the British Medical Journal , which in a signed editorial stated of the journalist, "It has taken the diligent scepticism of one man, standing outside medicine and science, to show that the paper was in fact an elaborate fraud." The scientific consensus is that there is no link between the MMR vaccine and autism and that the vaccine's benefits greatly outweigh its potential risks.In the wake of the measles outbreaks, which occurred in England in 1992, and on the basis of analyses of seroepidemiological data combined with mathematical modeling, British Health authorities predicted a major resurgence of measles in school-age children. Two strategies were then examined: either to target vaccination at all children without a history of prior measles vaccination or to immunize all children irrespective of vaccination history. In November 1994, the latter option was chosen and a national measles and rubella vaccination campaign, described as "one of the most ambitious vaccination initiatives that Britain has undertaken" was commenced: within one month, 92% of the 7.1 million schoolchildren in England aged 5–16 years received measles and rubella (MR) vaccine. In April 1994, Richard Barr , a solicitor, succeeded in winning legal aid for the pursuit of a class action lawsuit against the manufacturers of MMR vaccines under the UK Consumer Protection Act 1987 . The class action case was aimed at Aventis Pasteur , SmithKline Beecham , and Merck , manufacturers respectively of Immravax, Pluserix-MMR and MMR II. This suit, based on a claim that MMR is a defective product and should not have been used, was the first big class action lawsuit funded by the Legal Aid Board (which became the Legal Services Commission , which in turn was replaced by the Legal Aid Agency ) after its formation in 1988. Noticing two publications from Andrew Wakefield that explored the role of measles virus in Crohn's disease and inflammatory bowel disease , Barr contacted Wakefield for his expertise. According to Wakefield supporters, the two men first met on 6 January 1996. The Legal Services Commission halted proceedings in September 2003, citing a high probability of failure based on the medical evidence, bringing an end to the first case of research funding by the LSC. In the wake of the measles outbreaks, which occurred in England in 1992, and on the basis of analyses of seroepidemiological data combined with mathematical modeling, British Health authorities predicted a major resurgence of measles in school-age children. Two strategies were then examined: either to target vaccination at all children without a history of prior measles vaccination or to immunize all children irrespective of vaccination history. In November 1994, the latter option was chosen and a national measles and rubella vaccination campaign, described as "one of the most ambitious vaccination initiatives that Britain has undertaken" was commenced: within one month, 92% of the 7.1 million schoolchildren in England aged 5–16 years received measles and rubella (MR) vaccine. In April 1994, Richard Barr , a solicitor, succeeded in winning legal aid for the pursuit of a class action lawsuit against the manufacturers of MMR vaccines under the UK Consumer Protection Act 1987 . The class action case was aimed at Aventis Pasteur , SmithKline Beecham , and Merck , manufacturers respectively of Immravax, Pluserix-MMR and MMR II. This suit, based on a claim that MMR is a defective product and should not have been used, was the first big class action lawsuit funded by the Legal Aid Board (which became the Legal Services Commission , which in turn was replaced by the Legal Aid Agency ) after its formation in 1988. Noticing two publications from Andrew Wakefield that explored the role of measles virus in Crohn's disease and inflammatory bowel disease , Barr contacted Wakefield for his expertise. According to Wakefield supporters, the two men first met on 6 January 1996. The Legal Services Commission halted proceedings in September 2003, citing a high probability of failure based on the medical evidence, bringing an end to the first case of research funding by the LSC. Wakefield's paper "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children" was published in The Lancet on 28 February 1998. An investigation by journalist Brian Deer found that Wakefield had multiple undeclared conflicts of interest , had manipulated evidence, and had broken other ethical codes. [ which? ] Based on Deer's findings, Peter N. Steinmetz summarizes six fabrications and falsifications in the paper itself and in Wakefield's response in the areas of findings of non-specific colitis; behavioral symptoms; findings of regressive autism; ethics consent statement; conflict of interest statement; and methods of patient referral. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when The Lancet ' s editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010 and was struck off the Medical Register , meaning he could no longer practise as a doctor in the UK. In 2011, Deer provided further information on Wakefield's improper research practices to the British Medical Journal , which in a signed editorial described the original paper as fraudulent. The scientific consensus is that there is no link between the MMR vaccine and autism and that the vaccine's benefits greatly outweigh its risks. However, by the time that scientists had shown the narrative to be false, it had become part of the lay understanding of autism. The narrative was easy to understand and apparently consistent with anecdotal evidence of children receiving autism diagnoses shortly after having been vaccinated. By the time it was retracted, all authors other than Wakefield had requested their names be removed from the publication. Fiona Godlee , editor of The BMJ , said in January 2011: The original paper has received so much media attention, with such potential to damage public health, that it is hard to find a parallel in the history of medical science. Many other medical frauds have been exposed but usually more quickly after publication and on less important health issues.Observers [ who? ] have criticized the involvement of mass media in the controversy, what is known as ' science by press conference ', alleging that the media provided Wakefield's study with more credibility than it deserved. A March 2007 paper in BMC Public Health by Shona Hilton, Mark Petticrew, and Kate Hunt postulated that media reports on Wakefield's study had "created the misleading impression that the evidence for the link with autism was as substantial as the evidence against" through an attempt to create "balanced reporting". Earlier papers in Communication in Medicine and British Medical Journal concluded that media reports provided a misleading picture of the level of support for Wakefield's hypothesis. A 2007 editorial in Australian Doctor complained that some journalists had continued to defend Wakefield's study even after The Lancet had published the retraction by 10 of the study's 12 original authors, but noted that it was an investigative journalist, Brian Deer, who had played a leading role in exposing weaknesses in the study. PRWeek noted that after Wakefield was removed from the general medical register for misconduct in May 2010, 62% of respondents to a poll regarding the MMR controversy stated they did not feel that the media conducted responsible reporting on health issues. A New England Journal of Medicine article examining the history of anti-vaccine activists said that opposition to vaccines has existed since the 19th century, but "now the antivaccinationists' media of choice are typically television and the Internet, including its social media outlets, which are used to sway public opinion and distract attention from scientific evidence". The editorial characterized anti-vaccine activists as people who "tend toward complete mistrust of government and manufacturers, conspiratorial thinking, denialism, low cognitive complexity in thinking patterns, reasoning flaws, and a habit of substituting emotional anecdotes for data", including people who range from those "unable to understand and incorporate concepts of risk and probability into science-grounded decision making" and those "who use deliberate mistruths, intimidation, falsified data, and threats of violence". In a January 2011 editorial in The American Spectator , Robert M. Goldberg contended that evidence from the scientific community of issues with Wakefield's research "were undermined because the media allowed Wakefield and his followers to discredit the findings just by saying so". Seth Mnookin , author of The Panic Virus , also partly blames the media for presenting a false balance between scientific evidence and people's personal experiences: "Reporting fell into this 'on the one hand, on the other hand' fallacy, this notion that if you have two sides that are disagreeing, that means that you should present both of them with equal weight." Concerns have also been raised over the journal peer review system, which largely relies on trust among researchers, and the role of journalists reporting on scientific theories that they "are hardly in a position to question and comprehend". Neil Cameron, a historian who specializes in the history of science, writing for the Montreal Gazette , labeled the controversy a "failure of journalism" that resulted in unnecessary deaths, saying that: 1) The Lancet should not have published a study based on "statistically meaningless results" from only 12 cases; 2) the anti-vaccination crusade was continued by the satirical Private Eye magazine; and 3) a grapevine of worried parents and "nincompoop" celebrities fueled the widespread fears. The Gazette also reported that: There is no guarantee that debunking the original study is going to sway all parents. Medical experts are going to have to work hard to try to undo the damage inflicted by what is apparently a rogue medical researcher whose work was inadequately vetted by a top-ranked international journal. Folk epidemiology of autism refers to the popular beliefs about the origin of autism . Without direct informed knowledge of autism, a complex disorder, members of the public are easily influenced by rumors and misinformation presented in the mass media and repeated on social media and the internet . These misinformed beliefs persist even when contradicted by scientific evidence . Folk epidemiology persists because people seek, receive, and preferentially believe information that is consistent with their existing views; misjudge the reliability of their sources of information, and are misled by anecdotal evidence ; and tend not to revise their opinions even when their original sources of information are shown to be wrong. Folk epidemiology of autism refers to the popular beliefs about the origin of autism . Without direct informed knowledge of autism, a complex disorder, members of the public are easily influenced by rumors and misinformation presented in the mass media and repeated on social media and the internet . These misinformed beliefs persist even when contradicted by scientific evidence . Folk epidemiology persists because people seek, receive, and preferentially believe information that is consistent with their existing views; misjudge the reliability of their sources of information, and are misled by anecdotal evidence ; and tend not to revise their opinions even when their original sources of information are shown to be wrong. During the 1980s and 1990s, a number of lawsuits were brought against manufacturers of vaccines, alleging the vaccines had caused physical and mental disorders in children. While these lawsuits were unsuccessful, they did lead to a large jump in the costs of the MMR vaccine, and pharmaceutical companies sought legislative protections. In 1993, Merck KGaA became the only company willing to sell MMR vaccines in the United States and the United Kingdom. [ citation needed ] In June 2012, a local court in Rimini , Italy, ruled that the MMR vaccination had caused autism in a 15-month-old boy. The court relied heavily on the discredited Lancet paper and largely ignored the scientific evidence presented to it. The decision was appealed. On 13 February 2015, the decision was overturned by a Court of Appeals in Bologna. The MMR scare caused a low percentage of mumps vaccination (less than 30%), which resulted in outbreaks in Japan. There were up to 2002 measles-caused deaths in Japan while there were none in the UK, but the extra deaths were attributed to Japan's application of the vaccine at a later age. A spokesman for the Ministry of Health said that the discontinuation had no effect in measles, but also mentioning that there were more deaths by measles while MMR was being used. In 1994 the government dropped the vaccination requirement for measles and rubella due to the 1993 MMR scare. : 2 It has been called a "measles exporter" by the US Centers for Disease Control and Prevention. As another consequence of the scare, in 2003, 7 million schoolchildren had not been vaccinated against rubella. Autism rates continued to rise in Japan after the discontinuation of the MMR vaccine, which disproves any large-scale effect of vaccination, and means that the withdrawal of MMR in other countries is unlikely to cause a reduction in autism cases. The Japanese government does not recognize any link between MMR and autism. By 2003 it was still trying to find a combined vaccine to replace MMR. It was later discovered that some of the vaccines were administered after their expiry date and that the MMR compulsory vaccination was only retracted after the death of three children and more than 2000 reports of adverse effects. By 1993 the Japanese government had paid $160,000 in compensation to the families of each of the three dead children. Other parents received no compensation because the government said that it was unproven that the MMR vaccine had been the cause; they decided to sue the manufacturer instead of the government. The Osaka district court ruled on 13 March 2003 that the death of two children (among numerous other serious conditions) had been indeed caused by Japan's strain of Urabe MMR. In 2006, the Osaka High Court stated in another ruling that the state was responsible for failing to properly supervise a manufacturer of the measles-mumps-rubella vaccine, which caused severe side effects in children. Commenced before the Civil Procedure Rules were promulgated, the MMR Litigation had its status as group litigation achieved by the then Lord Chief Justice's practice direction of 8 July 1999. On 8 June 2007, the High Court judge, Justice Keith, put an end to the group litigation because the withdrawal of legal aid by the legal services commission had made the pursuit of most of the claimants impossible. He ruled that all but two claims against pharmaceutical companies must be discontinued. The judge stressed that his ruling did not amount to a rejection of any of the claims that MMR had seriously damaged the children concerned. A pressure group , JABS ( Justice, Awareness and Basic Support ), was established to represent families with children who, their parents said, were "vaccine-damaged". £15 million in public legal aid funding was spent on the litigation, of which £9.7 million went to solicitors and barristers , and £4.3 million to expert witnesses. The omnibus autism proceeding (OAP) is a coordinated proceeding before the Office of Special Masters of the U.S. Court of Federal Claims—commonly called the vaccine court . [ citation needed ] It is structured to facilitate the handling of nearly 5000 vaccine petitions involving claims that children who have received certain vaccinations have developed autism. The Petitioners' Steering Committee have claimed that MMR vaccines can cause autism, possibly in combination with thiomersal-containing vaccines . In 2007 three test cases were presented to test the claims about the combination; these cases failed. The vaccine court ruled against the plaintiffs in all three cases, stating that the evidence presented did not validate their claims that vaccinations caused autism in these specific patients or in general. In some cases, the plaintiffs' attorneys opted out of the Omnibus Autism Proceedings, which were concerned solely with autism, and issues concerned with bowel disorders; they argued their cases in the regular vaccine court. On 30 July 2007, the family of Bailey Banks, a child with pervasive developmental delay, won its case versus the Department of Health and Human Services. In a case listed as relating to "non-autistic developmental delay", Special Master Richard B. Abell ruled that the Banks had successfully demonstrated, "the MMR vaccine at issue actually caused the conditions from which Bailey suffered and continues to suffer." In his conclusion, he ruled that he was satisfied that MMR had caused a brain inflammation called acute disseminated encephalomyelitis (ADEM). He reached this conclusion because of two vaccine cases in 1994 and 2001, which had concluded, "ADEM can be caused by natural measles, mumps, and rubella infections, as well as by measles, mumps, and rubella vaccines." In other cases, attorneys did not claim that vaccines caused autism; they sought compensation for encephalopathy, encephalitis, or seizure disorders. In June 2012, a local court in Rimini , Italy, ruled that the MMR vaccination had caused autism in a 15-month-old boy. The court relied heavily on the discredited Lancet paper and largely ignored the scientific evidence presented to it. The decision was appealed. On 13 February 2015, the decision was overturned by a Court of Appeals in Bologna. The MMR scare caused a low percentage of mumps vaccination (less than 30%), which resulted in outbreaks in Japan. There were up to 2002 measles-caused deaths in Japan while there were none in the UK, but the extra deaths were attributed to Japan's application of the vaccine at a later age. A spokesman for the Ministry of Health said that the discontinuation had no effect in measles, but also mentioning that there were more deaths by measles while MMR was being used. In 1994 the government dropped the vaccination requirement for measles and rubella due to the 1993 MMR scare. : 2 It has been called a "measles exporter" by the US Centers for Disease Control and Prevention. As another consequence of the scare, in 2003, 7 million schoolchildren had not been vaccinated against rubella. Autism rates continued to rise in Japan after the discontinuation of the MMR vaccine, which disproves any large-scale effect of vaccination, and means that the withdrawal of MMR in other countries is unlikely to cause a reduction in autism cases. The Japanese government does not recognize any link between MMR and autism. By 2003 it was still trying to find a combined vaccine to replace MMR. It was later discovered that some of the vaccines were administered after their expiry date and that the MMR compulsory vaccination was only retracted after the death of three children and more than 2000 reports of adverse effects. By 1993 the Japanese government had paid $160,000 in compensation to the families of each of the three dead children. Other parents received no compensation because the government said that it was unproven that the MMR vaccine had been the cause; they decided to sue the manufacturer instead of the government. The Osaka district court ruled on 13 March 2003 that the death of two children (among numerous other serious conditions) had been indeed caused by Japan's strain of Urabe MMR. In 2006, the Osaka High Court stated in another ruling that the state was responsible for failing to properly supervise a manufacturer of the measles-mumps-rubella vaccine, which caused severe side effects in children. Commenced before the Civil Procedure Rules were promulgated, the MMR Litigation had its status as group litigation achieved by the then Lord Chief Justice's practice direction of 8 July 1999. On 8 June 2007, the High Court judge, Justice Keith, put an end to the group litigation because the withdrawal of legal aid by the legal services commission had made the pursuit of most of the claimants impossible. He ruled that all but two claims against pharmaceutical companies must be discontinued. The judge stressed that his ruling did not amount to a rejection of any of the claims that MMR had seriously damaged the children concerned. A pressure group , JABS ( Justice, Awareness and Basic Support ), was established to represent families with children who, their parents said, were "vaccine-damaged". £15 million in public legal aid funding was spent on the litigation, of which £9.7 million went to solicitors and barristers , and £4.3 million to expert witnesses. The omnibus autism proceeding (OAP) is a coordinated proceeding before the Office of Special Masters of the U.S. Court of Federal Claims—commonly called the vaccine court . [ citation needed ] It is structured to facilitate the handling of nearly 5000 vaccine petitions involving claims that children who have received certain vaccinations have developed autism. The Petitioners' Steering Committee have claimed that MMR vaccines can cause autism, possibly in combination with thiomersal-containing vaccines . In 2007 three test cases were presented to test the claims about the combination; these cases failed. The vaccine court ruled against the plaintiffs in all three cases, stating that the evidence presented did not validate their claims that vaccinations caused autism in these specific patients or in general. In some cases, the plaintiffs' attorneys opted out of the Omnibus Autism Proceedings, which were concerned solely with autism, and issues concerned with bowel disorders; they argued their cases in the regular vaccine court. On 30 July 2007, the family of Bailey Banks, a child with pervasive developmental delay, won its case versus the Department of Health and Human Services. In a case listed as relating to "non-autistic developmental delay", Special Master Richard B. Abell ruled that the Banks had successfully demonstrated, "the MMR vaccine at issue actually caused the conditions from which Bailey suffered and continues to suffer." In his conclusion, he ruled that he was satisfied that MMR had caused a brain inflammation called acute disseminated encephalomyelitis (ADEM). He reached this conclusion because of two vaccine cases in 1994 and 2001, which had concluded, "ADEM can be caused by natural measles, mumps, and rubella infections, as well as by measles, mumps, and rubella vaccines." In other cases, attorneys did not claim that vaccines caused autism; they sought compensation for encephalopathy, encephalitis, or seizure disorders. The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices; it is not known how much, if any, growth came from real changes in autism's prevalence , and no causal connection to the MMR vaccine has been demonstrated. In 2004, a meta review financed by the European Union assessed the evidence given in 120 other studies and considered unintended effects of the MMR vaccine, concluding that although the vaccine is associated with positive and negative side effects, a connection between MMR and autism was "unlikely". Also in 2004, a review article was published that concluded, "The evidence now is convincing that the measles–mumps–rubella vaccine does not cause autism or any particular subtypes of autistic spectrum disorder." A 2006 review of the literature regarding vaccines and autism found "[t]he bulk of the evidence suggests no causal relationship between the MMR vaccine and autism." A 2007 case study used the figure in Wakefield's 1999 letter to The Lancet alleging a temporal association between MMR vaccination and autism to illustrate how a graph can misrepresent its data, and gave advice to authors and publishers to avoid similar misrepresentations in the future. A 2007 review of independent studies performed after the publication of Wakefield et al. ' s original report found that the studies provided compelling evidence against the hypothesis that MMR is associated with autism. A review of the work conducted in 2004 for UK court proceedings but not revealed until 2007 found that the polymerase chain reaction analysis essential to the Wakefield et al. results was fatally flawed due to contamination, and that it could not have possibly detected the measles that it was supposed to have detected. A 2009 review of studies on links between vaccines and autism discussed the MMR vaccine controversy as one of three main hypotheses that epidemiological and biological studies failed to support. In 2012, the Cochrane Library published a review of dozens of scientific studies involving about 14,700,000 children, which found no credible evidence of an involvement of MMR with either autism or Crohn's disease . The article was updated in 2020 and again in 2021, with the authors stating, "We have observed an improvement in the quality of the design and reporting of safety outcomes in MMR and MMRV in recent years both pre- and post-marketing." A June 2014 meta-analysis involving more than 1.25 million children found "vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines ( thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder." In July 2014, a systematic review found "strong evidence that MMR vaccine is not associated with autism", and in March 2019, a large-scale study conducted by Statens Serum Institut following over 650,000 children for over 10 years found no link between the vaccine and autism, even among children with autistic siblings. After the controversy began, the MMR vaccination compliance dropped sharply in the United Kingdom, from 92% in 1996 to 84% in 2002. In some parts of London, it was as low as 61% in 2003, far below the rate needed to avoid an epidemic of measles. By 2006 coverage for MMR in the UK at 24 months was 85%, lower than the about 94% coverage for other vaccines. After vaccination rates dropped, the incidence of two of the three diseases increased greatly in the UK. In 1998 there were 56 confirmed cases of measles in the UK; in 2006 there were 449 in the first five months of the year, with the first death since 1992; cases occurred in inadequately vaccinated children. Mumps cases began rising in 1999 after years of very few cases, and by 2005 the United Kingdom was in a mumps epidemic with almost 5000 notifications in the first month of 2005 alone. The age group affected was too old to have received the routine MMR immunisations around the time the paper by Wakefield et al. was published, and too young to have contracted natural mumps as a child, and thus to achieve a herd immunity effect. With the decline in mumps that followed the introduction of the MMR vaccine, these individuals had not been exposed to the disease, but still had no immunity, either natural or vaccine induced. Therefore, as immunisation rates declined following the controversy and the disease re-emerged, they were susceptible to infection. Measles and mumps cases continued in 2006, at incidence rates 13 and 37 times greater than respective 1998 levels. Two children who underwent kidney transplantation in London were severely and permanently injured by measles encephalitis. Disease outbreaks also caused casualties in nearby countries. Three deaths and 1,500 cases were reported in the Irish outbreak of 2000, which occurred as a direct result of decreased vaccination rates following the MMR scare. In 2008, for the first time in 14 years, measles was declared endemic in the UK, meaning that the disease was sustained within the population; this was caused by the preceding decade's low MMR vaccination rates, which created a population of susceptible children who could spread the disease. MMR vaccination rates for English children were unchanged in 2007–08 from the year before, at too low a level to prevent serious measles outbreaks. In May 2008, a British 17-year-old with an underlying immunodeficiency died of measles. In 2008 Europe also faced a measles epidemic, including large outbreaks in Austria, Italy, and Switzerland. Following the January 2011 BMJ statements about Wakefield's fraud, Paul Offit , a pediatrician at Children's Hospital of Philadelphia and a "long-time critic of the dangers of the anti-vaccine movement", said, "that paper killed children", and Michael Smith of the University of Louisville , an "infectious diseases expert who has studied the autism controversy's effect on immunization rates", said "clearly, the results of this (Wakefield) study have had repercussions." In 2014, Laurie Garrett , senior fellow at the Council on Foreign Relations , blamed "Wakefieldism" for an increase in the number of unvaccinated children in countries such as Australia and New Zealand, saying, "Our data suggests that where Wakefield's message has caught on, measles follows." The New England Journal of Medicine said that antivaccinationist activities resulted in a high cost to society, "including damage to individual and community well-being from outbreaks of previously controlled diseases, withdrawal of vaccine manufacturers from the market, compromising of national security (in the case of anthrax and smallpox vaccines), and lost productivity". Costs to society from declining vaccination rates (in US dollars) were estimated by AOL's DailyFinance in 2011: A 2002–2003 outbreak of measles in Italy, "which led to the hospitalizations of more than 5,000 people, had a combined estimated cost between 17.6 million euros and 22.0 million euros". A 2004 outbreak of measles from "an unvaccinated student return[ing] from India in 2004 to Iowa was $142,452". A 2006 outbreak of mumps in Chicago, "caused by poorly immunized employees, cost the institution $262,788, or $29,199 per mumps case". A 2007 outbreak of mumps in Nova Scotia cost $3,511 per case. A 2008 outbreak of measles in San Diego, California cost $177,000, or $10,376 per case. In the United States, Jenny McCarthy blamed vaccinations for her son Evan's disorders and leveraged her celebrity status to warn parents of a link between vaccines and autism. Evan's disorder began with seizures and his improvement occurred after the seizures were treated, symptoms experts have noted are more consistent with Landau–Kleffner syndrome , often misdiagnosed as autism. After the Lancet article was discredited, McCarthy continued to defend Wakefield. An article in Salon.com called McCarthy "a menace" for her continued position that vaccines are dangerous. Bill Gates has reacted strongly to Wakefield and the work of anti-vaccination groups: Dr. [Andrew] Wakefield has been shown to have used absolutely fraudulent data. He had a financial interest in some lawsuits, he created a fake paper, the journal allowed it to run. All the other studies were done, showed no connection whatsoever again and again and again. So it's an absolute lie that has killed thousands of kids. Because the mothers who heard that lie, many of them didn't have their kids take either pertussis or measles vaccine, and their children are dead today. And so the people who go and engage in those anti-vaccine efforts—you know, they, they kill children. It's a very sad thing, because these vaccines are important. The proportion of children in England receiving the vaccine by the age of two fell to 91.2% in 2017–18, from 91.6% the year before. Only 87.2% of five-year-olds had received both MMR vaccines. With the onset of a large number of measles outbreaks in the United States in 2019, there is fear that parents who have not had their children vaccinated will help to spread infectious diseases in schools and universities where there are already other outbreaks. The New England Journal of Medicine said that antivaccinationist activities resulted in a high cost to society, "including damage to individual and community well-being from outbreaks of previously controlled diseases, withdrawal of vaccine manufacturers from the market, compromising of national security (in the case of anthrax and smallpox vaccines), and lost productivity". Costs to society from declining vaccination rates (in US dollars) were estimated by AOL's DailyFinance in 2011: A 2002–2003 outbreak of measles in Italy, "which led to the hospitalizations of more than 5,000 people, had a combined estimated cost between 17.6 million euros and 22.0 million euros". A 2004 outbreak of measles from "an unvaccinated student return[ing] from India in 2004 to Iowa was $142,452". A 2006 outbreak of mumps in Chicago, "caused by poorly immunized employees, cost the institution $262,788, or $29,199 per mumps case". A 2007 outbreak of mumps in Nova Scotia cost $3,511 per case. A 2008 outbreak of measles in San Diego, California cost $177,000, or $10,376 per case. In the United States, Jenny McCarthy blamed vaccinations for her son Evan's disorders and leveraged her celebrity status to warn parents of a link between vaccines and autism. Evan's disorder began with seizures and his improvement occurred after the seizures were treated, symptoms experts have noted are more consistent with Landau–Kleffner syndrome , often misdiagnosed as autism. After the Lancet article was discredited, McCarthy continued to defend Wakefield. An article in Salon.com called McCarthy "a menace" for her continued position that vaccines are dangerous. Bill Gates has reacted strongly to Wakefield and the work of anti-vaccination groups: Dr. [Andrew] Wakefield has been shown to have used absolutely fraudulent data. He had a financial interest in some lawsuits, he created a fake paper, the journal allowed it to run. All the other studies were done, showed no connection whatsoever again and again and again. So it's an absolute lie that has killed thousands of kids. Because the mothers who heard that lie, many of them didn't have their kids take either pertussis or measles vaccine, and their children are dead today. And so the people who go and engage in those anti-vaccine efforts—you know, they, they kill children. It's a very sad thing, because these vaccines are important. The proportion of children in England receiving the vaccine by the age of two fell to 91.2% in 2017–18, from 91.6% the year before. Only 87.2% of five-year-olds had received both MMR vaccines. With the onset of a large number of measles outbreaks in the United States in 2019, there is fear that parents who have not had their children vaccinated will help to spread infectious diseases in schools and universities where there are already other outbreaks.

Wiki

Chikungunya

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

Fifth disease

Erythema infectiosum , fifth disease , or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19 . Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect humans of all ages, only two out of ten individuals will present with physical symptoms. The name "fifth disease" comes from its place on the standard list of rash-causing childhood diseases , which also includes measles (first), scarlet fever (second), rubella (third), Dukes' disease (fourth, but is no longer widely accepted as distinct from scarlet fever), and roseola (sixth). Treatment is mostly supportive.Fifth disease starts with a low-grade fever, headache, rash, and cold-like symptoms, such as a runny or stuffy nose. These symptoms pass, then a few days later, the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks . This is a defining symptom of the infection in children (hence the name "slapped cheek disease"). Occasionally, the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children often develop a red, lacy rash on the rest of the body, with the upper arms, torso, and legs being the most common locations. The rash typically lasts a few days and may itch; some cases have been known to last for several weeks. Patients are usually no longer infectious once the rash has appeared. Teenagers and adults may present with a self-limited arthritis . It manifests in painful swelling of the joints that feels similar to arthritis. Older children and adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders. The disease is usually mild, but in certain risk groups and rare circumstances, it can have serious consequences:Fifth disease, also known as erythema infectiosum, is caused by parvovirus B19, which only infects humans. Infection by parvovirus B19 can lead to multiple clinical manifestations, but the most common is fifth disease. Parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus. Binding of B19V capsid to the cellular receptor globoside (Gb4Cer) results in a cascade of structural changes and subsequent signal transduction processes facilitating the entry of parvovirus B19 into the host cell. After gaining access to the host cell, B19V binds to glycosphingolipid globoside (blood group P antigen) targeting erythroid lineage in the bone marrow. Replication of viral genome and release of virus from infected cells lead to various complex effects on host's cellular environment such as induction of DNA damage, hijack of cell cycle and apoptosis (killing of infected cells). B19V DNA has been found in a wide range of tissues in healthy and diseased individuals indicates the persistence of B19V infection. According to a clinical microbiology review published by Jianming Qiu "Persistence of viral DNA has been detected in up to 50% of biopsy specimens of the spleen, lymph nodes, tonsils, liver, heart, synovial tissues, skin, brain, and testes, for decades after infection." Recovery from parvovirus B19 infection is achieved by production of IgM antibodies which are specific for virus and are generated 10–12 days after infection. After day 16, when signs of fifth disease (red rashes) and arthralgia (pain in joints) becomes apparent, specific anti B19 IgG is produced by immune cells. Production of serum anti B19 IgG keeps infection under control and facilitates the recovery of erythroid cell production in erythroid lineage cells that were targeted by parvovirus B19. The "slapped cheek" appearance of the rash can be suggestive of fifth disease, however, the rash can be mistaken with other skin related disease or infections. Blood samples testing can be definitive in confirming diagnosis. Anti-parvovirus B19 IgM antibody serum assay is the preferred method to detect previous infection. An antibody assay uses antibodies designed to detect parvovirus antigen or protein in blood circulation. The assay can result positive one week after initial infection. Negative results may prompt retesting in the future to rule out early sampling of blood serum. A positive result can also be indicative of an infection within the past two to six months. People acquire lifetime immunity if IgG antibodies are produced in response to parvovirus B19 exposure. Infection by parvovirus B19 can also be confirmed by isolation of viral DNA detected by PCR or direct hybridization . PCR Is considered significantly more sensitive to detecting viral antigen compared direct DNA hybridization. DNA hybridization assay can better detect variants of the parvovirus B19. There exists 3 biological similar genotypes of parvovirus B19, numbered one through three. The most common genotype circulating is genotype one. Laboratory tests can indicate complications of infection, including anemia, liver damage, and low platelet count. Fifth disease is transmitted primarily by respiratory secretions ( saliva , mucus , etc.), but can also be spread by contact with infected blood . The incubation period (the time between the initial infection and the onset of symptoms) is usually between 4 and 21 days. Individuals with fifth disease are most infectious before the onset of symptoms. Typically, school children, day-care workers, teachers, and parents are most likely to be exposed to the virus. When symptoms are evident, the risk of transmission is small; therefore, symptomatic individuals do not need to be isolated. Vertical transmission from maternal infection may also occur, which can lead to hydrops fetalis due to the infection's detrimental effects on red blood cell production. Treatment is supportive, as the infection is frequently self-limiting. No specific therapy is recommended. Antipyretics are commonly used to reduce fevers. In cases of arthropathy, such as those with arthritis or arthralgia, non-steroidal anti-inflammatories (NSAIDs) or other anti-inflammatories can be used. The rash usually does not itch, but can be mildly painful. The rash itself is not considered contagious. The infection generally lasts about 5 to 10 days. Stress, hot temperatures, exercise, and exposure to sunlight can contribute to reoccurrence within months of the initial infection. Upon resolution, immunity is considered life-long. Populations at greater risk of complications (see below) may need referral to a specialist. Anemia is a more severe complication that could result from parvovirus B19 infection and requires a blood transfusion as part of therapy. Fifth disease is a viral illness caused by Parvovirus B19. The illness is very common and self-limiting. The modes of transmission include respiratory droplets, blood, or mother to fetus. 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. Fifth Disease is most prevalent in children aged 5 to 15 years old. Fifth disease occurs at lower rates in adults. The virus spreads easily and once contracted, the body will begin developing lasting immunity to reinfection. The prevalence of antibodies is 50% in children and 70% to 85% in adults. The virus affects both men and women equally. During the spring and winter, epidemic outbreaks are most likely to occur. In the summer and fall, sporadic cases and outbreaks occur. The outbreaks most commonly occur in daycares and schools. The periodicity of the outbreak cycle is three-to-seven years. The risk of acquiring the viral illness increases when exposed to an infected person or contaminated blood. Individuals who have an occupation that requires close contact with infected people such as healthcare workers and teachers are at an increased risk of acquiring the viral illness. Another risk factor of fifth disease are immunocompromised individuals, those with anemia are at a higher risk of developing complications. Pregnant women are at risk for acquiring viral illness, especially during the first half of pregnancy. Though, complications are very rare and less than 5% of these cases will experience serious complications. The most common complication among pregnant women is anemia. In rare cases, severe anemia can occur, and a buildup of fluid can develop. A buildup of fluid can cause congestive heart failure or death. A blood infusion or induction may be necessary. No vaccine is available for human parvovirus B19, though attempts have been made to develop one. Parvovirus, the virus causing the fifth disease, was first discovered in 1975 by Yvonne Cossart. It, or a disease presenting similarly, was first described by Robert Willan in his book On Cutaneous Diseases in 1808 as "rubeola, sine catarrho". It was better defined by Anton Tschamer in 1889 as a rubella variant ( örtliche Rotheln ) and described it as abortive rubella, identified as a distinct condition in 1896 by Theodor Escherich , and given the name erythema infectiosum in 1899. The term fifth disease was coined in 1905 by the Russian–French physician Léon Cheinisse (1871–1924), who proposed a numbered classification of the six most common childhood exanthems . The virus was first described in 1957 at the University of Pennsylvania by Werner et al. A 2019 systematic review examined the rates of parvovirus B19 infection among daycare workers. Since transmission typically occurs through respiratory secretions, it was thought that daycare workers would be at an increased risk of infection because young children can spread saliva through drool. The systematic review indicates that daycare workers are at an increased risk for infection. Another review also supports the finding that daycare workers have an increased risk of contracting parvovirus B19 infection. A 2019 meta-analysis examined rates of parvovirus B19 infection among those with Sickle Cell Disease (SCD) using IgG and IgM antibody detection. Pooled data from Africa, Asia, and the Americas revealed a 48.8% parvovirus B19 infection prevalence among persons with SCD. Prevalence of infection was also determined by geographic location, where areas with reduced access to adequate housing had higher prevalence (Africa was 55.5%). A 2020 literature review also supports the finding that persons with SCD, as well as those with the blood disorder beta thalassemia , are at a higher risk of parvovirus B19 infection. There are some known complications associated with Fifth Disease relating to pregnancy. While parvovirus B19 is typically transmitted via respiratory secretions or hand to mouth contact, it has also been known to be passed from pregnant mothers to fetuses. Roughly 50-75% of all pregnant women are immune to parvovirus B19 while the remainder of women are susceptible to mild illness. A majority of fetuses who do contract parvovirus B19 show either no significant symptoms or complete resolution of the virus. However, the following serious complications are rare but possible: miscarriage, stillbirth, fetal anemia, hepatic failure, and abnormal neurodevelopment outcome. In some cases, fetuses would develop hydrops fetalis due to congenital parvovirus B19. This condition was studied as a determinant of later fetal outcomes, such as miscarriage or perinatal death, in 2016 systematic review. The review showed that those born with parvovirus B19 that caused hydrops fetalis did have an association with higher mortality risk and higher risk of complications. While the potential consequences of erythema infectiosum can be quite serious in pregnancy, mothers can be tested for immunity via the presence of IgG and IgM antibodies. In addition to fetuses, parvovirus B19 infection and its effects has been studied in adults as well. The virus has also been associated with the development of neurological complications, as identified in a systematic review in 2014. This analysis included a total of 89 studies covering complications in both the central and nervous system such as encephalitis, meningitis, and peripheral neuropathy. However, the specific pathophysiology of these complications has yet to be discovered but the review does encourage the use of antibody testing to determine a patient's risk. Infection of this virus is not limited to the nervous system. Parvovirus B19 has also been linked to cases of cardiac inflammation that can cause structural damage to the heart over time. If the damage progresses and is significant, cardiac cell death may occur. Individuals that are living with HIV are also susceptible to complications if infected due to being immunocompromised. While relatively rare, those who live with both HIV and parvovirus B19 infection will be unable to fight off the B19 virus. This can result in substantial loss of red blood cells and cause anemia.

Wiki

Chikungunya

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

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.

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Hand,_foot,_and_mouth_disease/html

Hand, foot, and mouth disease

Hand, foot, and mouth disease ( HFMD ) is a common infection caused by a group of enteroviruses . It typically begins with a fever and feeling generally unwell . This is followed a day or two later by flat discolored spots or bumps that may blister, on the hands, feet and mouth and occasionally buttocks and groin. Signs and symptoms normally appear 3–6 days after exposure to the virus . The rash generally resolves on its own in about a week. Fingernail and toenail loss may occur a few weeks later, but they will regrow with time. The viruses that cause HFMD are spread through close personal contact, through the air from coughing and the feces of an infected person. Contaminated objects can also spread the disease. Coxsackievirus A16 is the most common cause, and enterovirus 71 is the second-most common cause. Other strains of coxsackievirus and enterovirus can also be responsible. Some people may carry and pass on the virus despite having no symptoms of disease. Other animals are not involved. Diagnosis can often be made based on symptoms. Occasionally, a throat or stool sample may be tested for the virus. Most people with hand, foot, and mouth disease get better on their own in 7 to 10 days. Most cases require no specific treatment. No antiviral medication or vaccine is available, but development efforts are underway. For fever and for painful mouth sores, over-the-counter pain medications such as ibuprofen may be used, though aspirin should be avoided in children. The illness is usually not serious. Occasionally, intravenous fluids are given to children who are dehydrated. Very rarely, viral meningitis or encephalitis may complicate the disease. Because HFMD is normally mild, some jurisdictions allow children to continue to go to child care and schools as long as they have no fever or uncontrolled drooling with mouth sores, and as long as they feel well enough to participate in classroom activities. HFMD occurs in all areas of the world. It often occurs in small outbreaks in nursery schools or kindergartens. Large outbreaks have been occurring in Asia since 1997. It usually occurs during the spring, summer and fall months. Typically it occurs in children less than five years old but can occasionally occur in adults. HFMD should not be confused with foot-and-mouth disease (also known as hoof-and-mouth disease), which mostly affects livestock. Common constitutional signs and symptoms of the HFMD include fever, nausea, vomiting, feeling tired , generalized discomfort , loss of appetite , and irritability in infants and toddlers. Skin lesions frequently develop in the form of a rash of flat discolored spots and bumps which may be followed by vesicular sores with blisters on palms of the hands, soles of the feet, buttocks, and sometimes on the lips. The rash is rarely itchy for children, but can be extremely itchy for adults. Painful facial ulcers , blisters , or lesions may also develop in or around the nose or mouth . HFMD usually resolves on its own after 7–10 days. Most cases of the disease are relatively harmless, but complications including encephalitis, meningitis, and paralysis that mimics the neurological symptoms of polio can occur. The viruses that cause the disease are of the Picornaviridae family . Coxsackievirus A16 is the most common cause of HFMD. Enterovirus 71 (EV-71) is the second-most common cause. Many other strains of coxsackievirus and enterovirus can also be responsible. HFMD is highly contagious and is transmitted by nasopharyngeal secretions such as saliva or nasal mucus, by direct contact, or by fecal–oral transmission . It is possible to be infectious for days to weeks after the symptoms have resolved. Child care settings are the most common places for HFMD to be contracted because of toilet training, diaper changes, and the fact that children often put their hands into their mouths. HFMD is contracted through nose and throat secretions such as saliva, sputum, nasal mucus and as well as fluid in blisters, and stool. HFMD is highly contagious and is transmitted by nasopharyngeal secretions such as saliva or nasal mucus, by direct contact, or by fecal–oral transmission . It is possible to be infectious for days to weeks after the symptoms have resolved. Child care settings are the most common places for HFMD to be contracted because of toilet training, diaper changes, and the fact that children often put their hands into their mouths. HFMD is contracted through nose and throat secretions such as saliva, sputum, nasal mucus and as well as fluid in blisters, and stool. A diagnosis usually can be made by the presenting signs and symptoms alone. If the diagnosis is unclear, a throat swab or stool specimen may be taken to identify the virus by culture. The common incubation period (the time between infection and onset of symptoms) ranges from three to six days. Early detection of HFMD is important in preventing an outbreak in the pediatric population. Preventive measures include avoiding direct contact with infected individuals (including keeping infected children home from school), proper cleaning of shared utensils, disinfecting contaminated surfaces , and proper hand hygiene. These measures have been shown to be effective in decreasing the transmission of the viruses responsible for HFMD. Protective habits include hand washing and disinfecting surfaces in play areas. Breast-feeding has also shown to decrease rates of severe HFMD, though does not reduce the risk for the infection of the disease. A vaccine known as the EV71 vaccine is available to prevent HFMD in China as of December 2015 [ update ] . No vaccine is currently available in the United States. A vaccine known as the EV71 vaccine is available to prevent HFMD in China as of December 2015 [ update ] . No vaccine is currently available in the United States. Medications are usually not needed as hand, foot, and mouth disease is a viral disease that typically resolves on its own. Currently, there is no specific curative treatment for hand, foot and mouth disease. Disease management typically focuses on achieving symptomatic relief. Pain from the sores may be eased with the use of analgesic medications . Infection in older children, adolescents, and adults is typically mild and lasts approximately 1 week, but may occasionally run a longer course. Fever reducers can help decrease body temperature. [ citation needed ] A minority of individuals with hand, foot and mouth disease may require hospital admission due to complications such as inflammation of the brain , inflammation of the meninges , or acute flaccid paralysis . Non-neurologic complications such as inflammation of the heart , fluid in the lungs , or bleeding into the lungs may also occur. Complications from the viral infections that cause HFMD are rare, but require immediate medical treatment if present. HFMD infections caused by Enterovirus 71 tend to be more severe and are more likely to have neurologic or cardiac complications including death than infections caused by Coxsackievirus A16. Viral or aseptic meningitis can occur with HFMD in rare cases and is characterized by fever, headache , stiff neck , or back pain. The condition is usually mild and clears without treatment; however, hospitalization for a short time may be needed. Other serious complications of HFMD include encephalitis (inflammation of the brain), or flaccid paralysis in rare circumstances. Fingernail and toenail loss have been reported in children 4–8 weeks after having HFMD. The relationship between HFMD and the reported nail loss is unclear; however, it is temporary and nail growth resumes without treatment. Minor complications due to symptoms can occur such as dehydration, due to mouth sores causing discomfort with intake of foods and fluid. Hand, foot and mouth disease most commonly occurs in children under the age of 10 and more often under the age of 5, but it can also affect adults with varying symptoms. It tends to occur in outbreaks during the spring, summer, and autumn seasons. This is believed to be due to heat and humidity improving spread. HFMD is more common in rural areas than urban areas; however, socioeconomic status and hygiene levels need to be considered. Poor hygiene is a risk factor for HFMD. [ better source needed ] An outbreak of an illness referred to as tomato fever or tomato flu was identified in the Kollam district on May 6, 2022. The illness is endemic to Kerala , India and gets its name because of the red and round blisters it causes, which look like tomatoes . The disease may be a new variant of the viral HFMD or an effect of chikungunya or dengue fever . Flu may be a misnomer. The condition mainly affects children under the age of five. An article in The Lancet states that the appearance of the blisters is similar to that seen in monkey pox , and the illness is not thought to be related to SARS-CoV-2 . Symptoms, treatment and prevention are similar to HFMD. An outbreak of an illness referred to as tomato fever or tomato flu was identified in the Kollam district on May 6, 2022. The illness is endemic to Kerala , India and gets its name because of the red and round blisters it causes, which look like tomatoes . The disease may be a new variant of the viral HFMD or an effect of chikungunya or dengue fever . Flu may be a misnomer. The condition mainly affects children under the age of five. An article in The Lancet states that the appearance of the blisters is similar to that seen in monkey pox , and the illness is not thought to be related to SARS-CoV-2 . Symptoms, treatment and prevention are similar to HFMD. HFMD cases were first described clinically in Canada and New Zealand in 1957. The disease was termed "Hand Foot and Mouth Disease", by Thomas Henry Flewett , after a similar outbreak in 1960. Novel antiviral agents to prevent and treat infection with the viruses responsible for HFMD are currently under development. Preliminary studies have shown inhibitors of the EV-71 viral capsid to have potent antiviral activity.

Wiki

Chikungunya

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

Maculopapular rash

A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound: macules are small, flat discolored spots on the surface of the skin; and papules are small, raised bumps. It is also described as erythematous , or red. This type of rash is common in several diseases and medical conditions, including scarlet fever , measles , Ebola virus disease , rubella , HIV , secondary syphilis (Congenital syphilis, which is asymptomatic, the newborn may present this type of rash), erythrovirus ( parvovirus B19 ), chikungunya (alphavirus), zika , smallpox (which has been eradicated), varicella (when vaccinated persons exhibit symptoms from the modified form), heat rash , and sometimes in Dengue fever . It is also a common manifestation of a skin reaction to the antibiotic amoxicillin or chemotherapy drugs. Cutaneous infiltration of leukemic cells may also have this appearance. Maculopapular rash is seen in graft-versus-host disease (GVHD) developed after a hematopoietic stem cell transplant (bone marrow transplant), which can be seen within one week or several weeks after the transplant. In the case of GVHD, the maculopapular lesions may progress to a condition similar to toxic epidermal necrolysis . In addition, this is the type of rash that some patients presenting with Ebola virus hemorrhagic (EBO-Z) fever will reveal but can be hard to see on dark skin people. It is also seen in patients with Marburg hemorrhagic fever , a filovirus not unlike Ebola. This type of rash can be as a result of large doses of niacin or no-flush niacin (2000 – 2500 mg), [ citation needed ] used for the management of low HDL cholesterol. This type of rash can also be a symptom of Sea bather's eruption . This stinging, pruritic, maculopapular rash affects swimmers in some Atlantic locales (e.g., Florida, Caribbean, Long Island). It is caused by hypersensitivity to stings from the larvae of the sea anemone (e.g., Edwardsiella lineate ) or the thimble jellyfish ( Linuche unguiculata ). The rash appears where the bathing suit contacts the skin. This type of rash can also be a symptom of acute arsenic intoxication, appearing 2 weeks later.

Wiki

Chikungunya

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

Rubella virus

Rubella virus Rubella virus ( RuV ) is the pathogenic agent of the disease rubella , transmitted only between humans via the respiratory route, and is the main cause of congenital rubella syndrome when infection occurs during the first weeks of pregnancy . Rubella virus, scientific name Rubivirus rubellae , is a member of the genus Rubivirus and belongs to the family of Matonaviridae , whose members commonly have a genome of single-stranded RNA of positive polarity which is enclosed by an icosahedral capsid . As of 1999 [ update ] the molecular basis for the causation of congenital rubella syndrome was not yet completely clear, but in vitro studies with cell lines showed that rubella virus has an apoptotic effect on certain cell types. There is evidence for a p53 -dependent mechanism. Rubella virus ( Rubivirus rubellae ) is assigned to the Rubivirus genus. Until 2018, Rubiviruses were classified as part of the family Togaviridae , but have since been changed to be the sole genus of the family Matonaviridae . This family is named after George de Maton, who in 1814 first distinguished rubella from measles and scarlet fever . The change was made by the International Committee on the Taxonomy of Viruses (ICTV), the central governing body for viral classification . Matonaviridae remains part of the realm that it was already in as Togaviridae , Riboviria , because of its RNA genome and RNA dependent RNA polymerase . In 2020, Ruhugu virus and Rustrela virus joined Rubella virus as second and third of only three members of the genus Rubivirus . Neither of them are known to infect people. Until 2018, Rubiviruses were classified as part of the family Togaviridae , but have since been changed to be the sole genus of the family Matonaviridae . This family is named after George de Maton, who in 1814 first distinguished rubella from measles and scarlet fever . The change was made by the International Committee on the Taxonomy of Viruses (ICTV), the central governing body for viral classification . Matonaviridae remains part of the realm that it was already in as Togaviridae , Riboviria , because of its RNA genome and RNA dependent RNA polymerase . In 2020, Ruhugu virus and Rustrela virus joined Rubella virus as second and third of only three members of the genus Rubivirus . Neither of them are known to infect people. While alphavirus virions are spherical and contain an icosahedral nucleocapsid , RuV virions are pleiomorphic and do not contain icosahedral nucleocapsids. ICTV analyzed the sequence of RuV and compared its phylogeny to that of togaviruses. They concluded: Phylogenetic analysis of the RNA-dependent RNA polymerase of alphaviruses, rubella virus and other positive-sense RNA viruses shows the two genera within the Togaviridae are not monophyletic. In particular, rubella virus groups more closely with members of the families Benyviridae , Hepeviridae and Alphatetraviridae , along with several unclassified viruses, than it does with members of the family Togaviridae belonging to the genus Alphavirus . ICTV analyzed the sequence of RuV and compared its phylogeny to that of togaviruses. They concluded: Phylogenetic analysis of the RNA-dependent RNA polymerase of alphaviruses, rubella virus and other positive-sense RNA viruses shows the two genera within the Togaviridae are not monophyletic. In particular, rubella virus groups more closely with members of the families Benyviridae , Hepeviridae and Alphatetraviridae , along with several unclassified viruses, than it does with members of the family Togaviridae belonging to the genus Alphavirus . The spherical virus particles ( virions ) of Matonaviridae have a diameter of 50 to 70 nm and are covered by a lipid membrane ( viral envelope ), derived from the host cell membrane. There are prominent "spikes" (projections) of 6 nm composed of the viral envelope proteins E1 and E2 embedded in the membrane. The E1 glycoprotein is considered immunodominant in the humoral response induced against the structural proteins and contains both neutralizing and hemagglutinating determinants. Inside the lipid envelope is a capsid of 40 nm in diameter. The capsid protein (CP) has different functions. Its main tasks are the formation of homo oligomeres to form the capsid, and the binding of the genomic RNA. Further is it responsible for the aggregation of RNA in the capsid, it interacts with the membrane proteins E1 and E2 and binds the human host-protein p32 which is important for replication of the virus in the host. As opposed to alphaviruses the capsid does not undergo autoproteolysis, rather is it cut off from the rest of the polyprotein by the signal- peptidase . Production of the capsid happens at the surface of intracellular membranes simultaneously with the budding of the virus. Inside the lipid envelope is a capsid of 40 nm in diameter. The capsid protein (CP) has different functions. Its main tasks are the formation of homo oligomeres to form the capsid, and the binding of the genomic RNA. Further is it responsible for the aggregation of RNA in the capsid, it interacts with the membrane proteins E1 and E2 and binds the human host-protein p32 which is important for replication of the virus in the host. As opposed to alphaviruses the capsid does not undergo autoproteolysis, rather is it cut off from the rest of the polyprotein by the signal- peptidase . Production of the capsid happens at the surface of intracellular membranes simultaneously with the budding of the virus. The genome has 9,762 nucleotides and encodes 2 nonstructural polypeptides (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third. Both envelope proteins E1 and E2 are glycosylated . There are three sites that are highly conserved in Matonaviruses: a stem-and-loop structure at the 5' end of the genome, a 51-nucleotide conserved sequence near the 5' end of the genome and a 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequences are present in the rubella genome. The genome encodes several non-coding RNA structures; among them is the rubella virus 3' cis-acting element , which contains multiple stem-loops , one of which has been found to be essential for viral replication. The only significant region of homology between rubella and the alphaviruses is located at the NH2 terminus of non structural protein 3. This sequence has helicase and replicase activity. In the rubella genome these occur in the opposite orientation to that found in the alphaviruses indicating that a genome rearrangement has occurred. The genome has the highest G+C content of any currently known single stranded RNA virus (~70%). Despite this high GC content its codon use is similar to that of its human host.The viruses attach to the cell surface via specific receptors and are taken up by an endosome being formed. At the neutral pH outside of the cell the E2 envelope protein covers the E1 protein. The dropping pH inside the endosome frees the outer domain of E1 and causes the fusion of the viral envelope with the endosomal membrane. Thus, the capsid reaches the cytosol , decays and releases the genome The +ssRNA ( positive , single-stranded RNA ) at first only acts as a template for the translation of the non-structural proteins, which are synthesized as a large polyprotein and are then cut into single proteins. The sequences for the structural proteins are first replicated by the viral RNA polymerase (Replicase) via a complementary − ssRNA as a template and translated as a separate short mRNA. This short subgenomic RNA is additionally packed in a virion. Translation of the structural proteins produces a large polypeptide (110 Dalton ). This is then endoproteolytically cut into E1, E2 and the capsid protein. E1 and E2 are type I transmembrane proteins which are transported into the endoplasmatic reticulum (ER) with the help of an N-terminal signal sequence. From the ER the heterodimeric E1·E2-complex reaches the Golgi apparatus , where the budding of new virions occurs (unlike alpha viruses, where budding occurs at the plasma membrane. The capsid proteins on the other hand stay in the cytoplasm and interact with the genomic RNA, together forming the capsid. RuV is transmitted via respiration between humans. On the basis of differences in the sequence of the E1 protein, two genotypes have been described which differ by 8 - 10%. These have been subdivided into 13 recognised genotypes - 1a, 1B, 1C, 1D, 1E, 1F, 1G, 1h, 1i, 1j, 2A, 2B and 2C. For typing, the WHO recommends a minimum window that includes nucleotides 8731 to 9469. Genotypes 1a, 1E, 1F, 2A and 2B have been isolated in China . Genotype 1j has only been isolated from Japan and the Philippines . Genotype 1E is found in Africa , the Americas , Asia and Europe . Genotype 1G has been isolated in Belarus , Cote d'Ivoire and Uganda . Genotype 1C is endemic only in Central and South America. Genotype 2B has been isolated in South Africa . Genotype 2C has been isolated in Russia .David M. Knipe, Peter M. Howley et al. (eds.): Fields Virology 4. Auflage, Philadelphia 2001 C.M. Fauquet, M.A. Mayo et al.: Eighth Report of the International Committee on Taxonomy of Viruses , London San Diego 2005

Wiki

Chikungunya

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

Wolbachia

" Candidatus Wolbachia bourtzisii " Ramirez-Puebla et al. 2015 " Candidatus Wolbachia brugii " Ramirez-Puebla et al. 2015 " Candidatus Wolbachia collembolicola " Ramirez-Puebla et al. 2015 " Candidatus Wolbachia ivorensis " Ehounoud et al. 2016 Wolbachia melophagi (Nöller 1917) Philip 1956 (Approved Lists 1980) " Candidatus Wolbachia multihospitum " Ramirez-Puebla et al. 2015 " Candidatus Wolbachia onchocercicola " Ramirez-Puebla et al. 2015 Wolbachia pipientis Hertig 1936 (Approved Lists 1980) Wolbachia is a genus of gram-negative bacteria that can either infect many species of arthropod as an intracellular parasite , or act as a mutualistic microbe in filarial nematodes . It is one of the most common parasitic microbes of arthropods, and is possibly the most common reproductive parasite in the biosphere . Its interactions with its hosts are often complex. Some host species cannot reproduce, or even survive, without Wolbachia colonisation . One study concluded that more than 16% of neotropical insect species carry bacteria of this genus, and as many as 25 to 70% of all insect species are estimated to be potential hosts. The genus was first identified in 1924 by Marshall Hertig and Simeon Burt Wolbach in the common house mosquito . They described it as "a somewhat pleomorphic , rodlike , Gram-negative , intracellular organism [that] apparently infects only the ovaries and testes ". Hertig formally described the species in 1936, and proposed both the generic and specific names: Wolbachia pipientis . Research on Wolbachia intensified after 1971, when Janice Yen and A. Ralph Barr of UCLA discovered that Culex mosquito eggs were killed by a cytoplasmic incompatibility when the sperm of Wolbachia -infected males fertilized infection-free eggs. The genus Wolbachia is of considerable interest today due to its ubiquitous distribution, its many different evolutionary interactions, and its potential use as a biocontrol agent . Phylogenetic studies have shown that Wolbachia persica (now Francisella persica ) was closely related to species in the genus Francisella and that Wolbachia melophagi (now Bartonella melophagi ) was closely related to species in the genus Bartonella , leading to a transfer of these species to these respective genera. Furthermore, unlike true Wolbachia , which needs a host cell to multiply, F. persica and B. melophagi can be cultured on agar plates . These bacteria can infect many different types of organs, but are most notable for the infections of the testes and ovaries of their hosts. Wolbachia species are ubiquitous in mature eggs, but not mature sperm. Only infected females, therefore, pass the infection on to their offspring. Wolbachia bacteria maximize their spread by significantly altering the reproductive capabilities of their hosts, with four different phenotypes :Several host species, such as those within the genus Trichogramma , are so dependent on sexual differentiation of Wolbachia that they are unable to reproduce effectively without the bacteria in their bodies, and some might even be unable to survive uninfected. One study on infected woodlice showed the broods of infected organisms had a higher proportion of females than their uninfected counterparts. Wolbachia , especially Wolbachia -caused cytoplasmic incompatibility, may be important in promoting speciation. Wolbachia strains that distort the sex ratio may alter their host's pattern of sexual selection in nature, and also engender strong selection to prevent their action, leading to some of the fastest examples of natural selection in natural populations. The male killing and feminization effects of Wolbachia infections can also lead to speciation in their hosts. For example, populations of the pill woodlouse, Armadillidium vulgare which are exposed to the feminizing effects of Wolbachia , have been known to lose their female-determining chromosome. In these cases, only the presence of Wolbachia can cause an individual to develop into a female. Cryptic species of ground wētā ( Hemiandrus maculifrons complex) are host to different lineages of Wolbachia which might explain their speciation without ecological or geographical separation. The enzyme aromatase is found to mediate sex-change in many species of fish. Wolbachia can affect the activity of aromatase in developing fish embryos. The enzyme aromatase is found to mediate sex-change in many species of fish. Wolbachia can affect the activity of aromatase in developing fish embryos. Wolbachia may transfer from prey to predator through the digestive system. To do so, Wolbachia needs to first survive through the lumen secretion and then enter the host tissue through the gut epithelium. This route does not seem to occur frequently due to little evidence. This may be one of the most common routes of Wolbachia host shifts. Compared to predator-prey interactions, the physical association between the host and parasites typically lasts longer, occurs at various developmental stages, and enables Wolbachia to directly contact various tissues. Since this interaction may expose both sides to microbial exchange, one strategy for understanding the direction of transfer is to assess Wolbachia 's presence in close relatives on both sides, as the donor side generally has a larger diversity of infection. One parasitoid species can infect multiple shared hosts, and one host species can infect multiple parasitoids. For instance, parthenogenesis-inducing Wolbachia can spread between Trichogramma parasitoid wasps sharing host eggs. Parasites can also serve as a vector between infected and uninfected hosts without being infected. When the mouthparts and ovipositors of aphelinid parasitoid wasps become contaminated through feeding Wolbachia -infected Bemisia tabaci , it can infect the next host. This route applies to microbes that can survive either within or on the surface of the food. Experiments demonstrated that the Wolbachia wAlbB strain can survive extracellularly for up to 7 days, and up to 50 days for some strains in cotton leaf phloem vessels. Plants are one of the best platforms for this route. By physical contact between arthropod mouthparts and plant tissue, the Wolbachia inhabiting the salivary glands of some insects may be transferred to the plants. As a result, arthropod species feeding on the same plants may share common Wolbachia strains. Other insect food sources may also mediate Wolbachia horizontal transfer, such as the sharing of dung patches between two Malagasy dung beetle species. The pathogen-associated molecular patterns (PAMPs) in the bacteria, such as peptidoglycan, can activate the host's innate immune responses. In response, some Wolbachia strains have a unique functional peptidoglycan amidase (AmiDwol) that cleaves its bacterial cell wall so that it can escape from immune responses. Besides the peptidoglycans, cell-to-cell movements of Wolbachia can also cause oxidative stress to the host and trigger the host's immune response. Therefore, Wolbachia has a triple-layer vacuole that acts as a mechanical shield to protect it from cellular immune responses. Vertical transmission requires Wolbachia to reach germ line cells and maintain in the zygote. Wolbachia may initially occupy somatic stem cells as a stable reservoir and then use the host's vitellogenin transovarial transportation system to enter the oocyte. Once Wolbachia enter the zygote, they need to reach important host tissues without disrupting the embryo's development. This can be achieved using the host cytoskeleton, by bundling Wolbachia protein WD0830 to host actin filaments. They can also increase the division rate of germ-line stem cells to localize and increase their titer. Under natural conditions, successful vertical transmission of Wolbachia is challenging. Invasion of a new population likely stems from specific phenotypic effects, including reproductive manipulations and/or providing direct fitness benefits to their female hosts. Upon transferring into a new host, Wolbachia may retain its original phenotypic effects, induce a different phenotype, or have no detectable effect. For instance, a strain that induce male killing in the moth Cadra cautella induced Cytoplasmic incompatibility in a novel moth host Ephestia kuehniella . Wolbachia may transfer from prey to predator through the digestive system. To do so, Wolbachia needs to first survive through the lumen secretion and then enter the host tissue through the gut epithelium. This route does not seem to occur frequently due to little evidence. This may be one of the most common routes of Wolbachia host shifts. Compared to predator-prey interactions, the physical association between the host and parasites typically lasts longer, occurs at various developmental stages, and enables Wolbachia to directly contact various tissues. Since this interaction may expose both sides to microbial exchange, one strategy for understanding the direction of transfer is to assess Wolbachia 's presence in close relatives on both sides, as the donor side generally has a larger diversity of infection. One parasitoid species can infect multiple shared hosts, and one host species can infect multiple parasitoids. For instance, parthenogenesis-inducing Wolbachia can spread between Trichogramma parasitoid wasps sharing host eggs. Parasites can also serve as a vector between infected and uninfected hosts without being infected. When the mouthparts and ovipositors of aphelinid parasitoid wasps become contaminated through feeding Wolbachia -infected Bemisia tabaci , it can infect the next host. This route applies to microbes that can survive either within or on the surface of the food. Experiments demonstrated that the Wolbachia wAlbB strain can survive extracellularly for up to 7 days, and up to 50 days for some strains in cotton leaf phloem vessels. Plants are one of the best platforms for this route. By physical contact between arthropod mouthparts and plant tissue, the Wolbachia inhabiting the salivary glands of some insects may be transferred to the plants. As a result, arthropod species feeding on the same plants may share common Wolbachia strains. Other insect food sources may also mediate Wolbachia horizontal transfer, such as the sharing of dung patches between two Malagasy dung beetle species. Wolbachia may transfer from prey to predator through the digestive system. To do so, Wolbachia needs to first survive through the lumen secretion and then enter the host tissue through the gut epithelium. This route does not seem to occur frequently due to little evidence. This may be one of the most common routes of Wolbachia host shifts. Compared to predator-prey interactions, the physical association between the host and parasites typically lasts longer, occurs at various developmental stages, and enables Wolbachia to directly contact various tissues. Since this interaction may expose both sides to microbial exchange, one strategy for understanding the direction of transfer is to assess Wolbachia 's presence in close relatives on both sides, as the donor side generally has a larger diversity of infection. One parasitoid species can infect multiple shared hosts, and one host species can infect multiple parasitoids. For instance, parthenogenesis-inducing Wolbachia can spread between Trichogramma parasitoid wasps sharing host eggs. Parasites can also serve as a vector between infected and uninfected hosts without being infected. When the mouthparts and ovipositors of aphelinid parasitoid wasps become contaminated through feeding Wolbachia -infected Bemisia tabaci , it can infect the next host. This route applies to microbes that can survive either within or on the surface of the food. Experiments demonstrated that the Wolbachia wAlbB strain can survive extracellularly for up to 7 days, and up to 50 days for some strains in cotton leaf phloem vessels. Plants are one of the best platforms for this route. By physical contact between arthropod mouthparts and plant tissue, the Wolbachia inhabiting the salivary glands of some insects may be transferred to the plants. As a result, arthropod species feeding on the same plants may share common Wolbachia strains. Other insect food sources may also mediate Wolbachia horizontal transfer, such as the sharing of dung patches between two Malagasy dung beetle species. The pathogen-associated molecular patterns (PAMPs) in the bacteria, such as peptidoglycan, can activate the host's innate immune responses. In response, some Wolbachia strains have a unique functional peptidoglycan amidase (AmiDwol) that cleaves its bacterial cell wall so that it can escape from immune responses. Besides the peptidoglycans, cell-to-cell movements of Wolbachia can also cause oxidative stress to the host and trigger the host's immune response. Therefore, Wolbachia has a triple-layer vacuole that acts as a mechanical shield to protect it from cellular immune responses. Vertical transmission requires Wolbachia to reach germ line cells and maintain in the zygote. Wolbachia may initially occupy somatic stem cells as a stable reservoir and then use the host's vitellogenin transovarial transportation system to enter the oocyte. Once Wolbachia enter the zygote, they need to reach important host tissues without disrupting the embryo's development. This can be achieved using the host cytoskeleton, by bundling Wolbachia protein WD0830 to host actin filaments. They can also increase the division rate of germ-line stem cells to localize and increase their titer. Under natural conditions, successful vertical transmission of Wolbachia is challenging.Invasion of a new population likely stems from specific phenotypic effects, including reproductive manipulations and/or providing direct fitness benefits to their female hosts. Upon transferring into a new host, Wolbachia may retain its original phenotypic effects, induce a different phenotype, or have no detectable effect. For instance, a strain that induce male killing in the moth Cadra cautella induced Cytoplasmic incompatibility in a novel moth host Ephestia kuehniella . Wolbachia infection has been linked to viral resistance in Drosophila melanogaster , Drosophila simulans , and mosquito species. Flies, including mosquitoes, infected with the bacteria are more resistant to RNA viruses such as Drosophila C virus , norovirus , flock house virus , cricket paralysis virus , chikungunya virus , and West Nile virus . In the common house mosquito, higher levels of Wolbachia were correlated with more insecticide resistance. In leafminers of the species Phyllonorycter blancardella , Wolbachia bacteria help their hosts produce green islands on yellowing tree leaves, that is, small areas of leaf remaining fresh, allowing the hosts to continue feeding while growing to their adult forms. Larvae treated with tetracycline , which kills Wolbachia , lose this ability and subsequently only 13% emerge successfully as adult moths. Muscidifurax uniraptor , a parasitoid wasp , also benefits from hosting Wolbachia bacteria. In the parasitic filarial nematode species responsible for elephantiasis , such as Brugia malayi and Wuchereria bancrofti , Wolbachia has become an obligate endosymbiont and provides the host with chemicals necessary for its reproduction and survival. Elimination of the Wolbachia symbionts through antibiotic treatment therefore prevents reproduction of the nematode, and eventually results in its premature death. Some Wolbachia species that infect arthropods also provide some metabolic provisioning to their hosts. In Drosophila melanogaster , Wolbachia is found to mediate iron metabolism under nutritional stress and in Cimex lectularius , the Wolbachia strain cCle helps the host to synthesize B vitamins . Some Wolbachia strains have increased their prevalence by increasing their hosts' fecundity. Wolbachia strains captured from 1988 in southern California still induce a fecundity deficit, but nowadays the fecundity deficit is replaced with a fecundity advantage such that infected Drosophila simulans produces more offspring than the uninfected ones. Wolbachia often manipulates host reproduction and life-history in a way that favours its own propagation. In the Pharaoh ant , Wolbachia infection correlates with increased colony-level production of reproductives (i.e., greater reproductive investment), and earlier onset of reproductive production (i.e., shorter life-cycle). Infected colonies also seem to grow more rapidly. There is substantial evidence that the presence of Wolbachia that induce parthenogenesis have put pressure on species to reproduce primarily or entirely this way. Additionally, Wolbachia has been seen to decrease the lifespan of Aedes aegypti , carriers of mosquito-borne diseases, and it decreases their efficacy of pathogen transmission because older mosquitoes are more likely to have become carriers of one of those diseases. This has been exploited as a method for pest control.The first Wolbachia genome to be determined was that of strain wMel, which infects D. melanogaster fruit flies. This genome was sequenced at The Institute for Genomic Research in a collaboration between Jonathan Eisen and Scott O'Neill. The second Wolbachia genome to be determined was of strain wBm, which infects Brugia malayi nematodes. Genome sequencing projects for several other Wolbachia strains are in progress. Wolbachia species also harbor a bacteriophage called bacteriophage WO or phage WO. Comparative sequence analyses of bacteriophage WO offer some of the most compelling examples of large-scale horizontal gene transfer between Wolbachia coinfections in the same host. It is the first bacteriophage implicated in frequent lateral transfer between the genomes of bacterial endosymbionts . Gene transfer by bacteriophages could drive significant evolutionary change in the genomes of intracellular bacteria that were previously considered highly stable or prone to loss of genes over time. Wolbachia also transfers genes to the host. A nearly complete copy of the Wolbachia genome sequence was found within the genome sequence of the fruit fly Drosophila ananassae and large segments were found in seven other Drosophila species. In an application of DNA barcoding to the identification of species of Protocalliphora flies, several distinct morphospecies had identical cytochrome c oxidase I gene sequences, most likely through horizontal gene transfer (HGT) by Wolbachia species as they jump across host species. As a result, Wolbachia can cause misleading results in molecular cladistical analyses. It is estimated that between 20 and 50 percent of insect species have evidence of HGT from Wolbachia —passing from microbes to animal (i.e. insects). Wolbachia species also harbor a bacteriophage called bacteriophage WO or phage WO. Comparative sequence analyses of bacteriophage WO offer some of the most compelling examples of large-scale horizontal gene transfer between Wolbachia coinfections in the same host. It is the first bacteriophage implicated in frequent lateral transfer between the genomes of bacterial endosymbionts . Gene transfer by bacteriophages could drive significant evolutionary change in the genomes of intracellular bacteria that were previously considered highly stable or prone to loss of genes over time. Wolbachia also transfers genes to the host. A nearly complete copy of the Wolbachia genome sequence was found within the genome sequence of the fruit fly Drosophila ananassae and large segments were found in seven other Drosophila species. In an application of DNA barcoding to the identification of species of Protocalliphora flies, several distinct morphospecies had identical cytochrome c oxidase I gene sequences, most likely through horizontal gene transfer (HGT) by Wolbachia species as they jump across host species. As a result, Wolbachia can cause misleading results in molecular cladistical analyses. It is estimated that between 20 and 50 percent of insect species have evidence of HGT from Wolbachia —passing from microbes to animal (i.e. insects). The small non-coding RNAs WsnRNA-46 and WsnRNA-59 in Wolbachia were detected in Aedes aegypti mosquitoes and Drosophila melanogaster . The small RNAs (sRNAs) may regulate bacterial and host genes. Highly conserved intragenic region sRNA called ncrwmel02 was also identified in Wolbachia pipientis. It is expressed in four different strains in a regulated pattern that differs according to the sex of the host and the tissue localisation. This suggested that the sRNA may play important roles in the biology of Wolbachia. Outside of insects, Wolbachia infects a variety of isopod species, spiders , mites , and many species of filarial nematodes (a type of parasitic worm ), including those causing onchocerciasis (river blindness) and elephantiasis in humans, as well as heartworms in dogs. Not only are these disease-causing filarial worms infected with Wolbachia , but Wolbachia also seems to play an inordinate role in these diseases. A large part of the pathogenicity of filarial nematodes is due to host immune response toward their Wolbachia . Elimination of Wolbachia from filarial nematodes generally results in either death or sterility of the nematode. Consequently, current strategies for control of filarial nematode diseases include elimination of their symbiotic Wolbachia via the simple doxycycline antibiotic, rather than directly killing the nematode with often more toxic antinematode medications. Naturally existing strains of Wolbachia have been shown to be a route for vector control strategies because of their presence in arthropod populations, such as mosquitoes. Due to the unique traits of Wolbachia that cause cytoplasmic incompatibility , some strains are useful to humans as a promoter of genetic drive within an insect population. Wolbachia -infected females are able to produce offspring with uninfected and infected males; however, uninfected females are only able to produce viable offspring with uninfected males. This gives infected females a reproductive advantage that is greater the higher the frequency of Wolbachia in the population. Computational models predict that introducing Wolbachia strains into natural populations will reduce pathogen transmission and reduce overall disease burden. An example includes a life-shortening Wolbachia that can be used to control dengue virus and malaria by eliminating the older insects that contain more parasites. Promoting the survival and reproduction of younger insects lessens selection pressure for evolution of resistance. In addition, some Wolbachia strains are able to directly reduce viral replication inside the insect. For dengue they include wAllbB and wMelPop with Aedes aegypti , wMel with Aedes albopictus and Aedes aegypti . Wolbachia has also been identified to inhibit replication of chikungunya virus (CHIKV) in A. aegypti . The w Mel strain of Wolbachia pipientis significantly reduced infection and dissemination rates of CHIKV in mosquitoes, compared to Wolbachia uninfected controls and the same phenomenon was observed in yellow fever virus infection converting this bacterium in an excellent promise for YFV and CHIKV suppression. Wolbachia also inhibits the secretion of West Nile virus (WNV) in cell line Aag2 derived from A. aegypti cells. The mechanism is somewhat novel, as the bacteria actually enhances the production of viral genomic RNA in the cell line Wolbachia . Also, the antiviral effect in intrathoracically infected mosquitoes depends on the strain of Wolbachia , and the replication of the virus in orally fed mosquitoes was completely inhibited in wMelPop strain of Wolbachia . The effect of Wolbachia infection on virus replication in insect hosts is complex and depends on the Wolbachia strain and virus species. While several studies have indicated consistent refractory phenotypes of Wolbachia infection on positive-sense RNA viruses in Drosophila melanogaster , the yellow fever mosquito Aedes aegypti and the Asian tiger mosquito Aedes albopictus , this effect is not seen in DNA virus infection and in some cases Wolbachia infection has been associated or shown to increase single stranded DNA and double-stranded DNA virus infection. There is also currently no evidence that Wolbachia infection restricts any tested negative-sense RNA viruses indicating Wolbachia would be unsuitable for restriction of negative-sense RNA arthropod borne viruses. Wolbachia infection can also increase mosquito resistance to malaria, as shown in Anopheles stephensi where the w AlbB strain of Wolbachia hindered the lifecycle of Plasmodium falciparum . However, Wolbachia infections can also enhance pathogen transmission. Wolbachia has enhanced multiple arboviruses in Culex tarsalis mosquitoes. In another study, West Nile Virus (WNV) infection rate was significantly higher in Wolbachia (strain wAlbB)-infected C. tarsalis compared to controls. Wolbachia may induce reactive oxygen species –dependent activation of the Toll (gene family) pathway, which is essential for activation of antimicrobial peptides , defensins , and cecropins that help to inhibit virus proliferation. Conversely, certain strains actually dampen the pathway, leading to higher replication of viruses. One example is with strain wAlbB in Culex tarsalis , where infected mosquitoes actually carried the west nile virus (WNV) more frequently. This is because wAlbB inhibits REL1, an activator of the antiviral Toll immune pathway. As a result, careful studies of the Wolbachia strain and ecological consequences must be done before releasing artificially-infected mosquitoes in the environment. The World Mosquito Program (WMP) uses Wolbachia strain wMel to infect Aedes mosquitos. The mixed-sex mosquitos are intended to infect the local population with wMel, giving them transmission resistance. In 2014, WMP released infected mosquitos in Townsville , an Australia city with 187,000 inhabitants plagued by dengue. For four years after introduction, no cases of dengue were reported. Trials in much smaller areas had been carried out, but a larger area had not been tested. No environmental ill-effects were reported. The cost was A$ 15 per inhabitant, but it was hoped that it could be reduced to US$ 1 in poorer countries with lower labor costs. In 2016, WMP scientist Scott Ritchie proposed using wMel mosquitos to combat the spread of the Zika virus . A study reported that Wolbachia wMel has the ability to block Zika in Brazil. In October 2016, it was announced that US$18 million in funding was being allocated for the use of Wolbachia -infected mosquitoes to fight Zika and dengue viruses. Deployment is slated for early 2017 in Colombia and Brazil. Between 2016 and 2020, WMP conducted its first randomized controlled trial in Yogyakarta , an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist Adi Utarini announced that the trial showed a 77% reduction in dengue cases compared to the control areas. This trial was the "strongest evidence yet" for the technique. In 2017 – 2019, WMP released mosquitos in Niterói, Brazil. In March 2023, Brazil's Oswaldo Cruz Foundation signed an agreement with WMP to provide funds for a large "mosquito factory" producing infected insects. Another method to use Wolbachia in mosquitos exploits the cytoplamic incompatibility between infected males and uninfected females. If an uninfected female mates with an infected male, her eggs become infertile. With enough infected males released, the mosquito population would be reduced temporarily. Verily , the life sciences arm of Google's parent company Alphabet Inc. , uses this method. In July 2017, it announced a plan to release about 20 million Wolbachia -infected male Aedes aegypti mosquitoes in Fresno , California , in an attempt to combat the Zika virus. Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male Wolbachia mosquitoes for Phase 2 of its study to suppress the urban Aedes aegypti mosquito population and fight dengue. On November 3, 2017, the US Environmental Protection Agency (EPA) registered Mosquito Mate, Inc. to release Wolbachia strain "ZAP"-infected male mosquitoes in 20 US states and the District of Columbia. Outside of insects, Wolbachia infects a variety of isopod species, spiders , mites , and many species of filarial nematodes (a type of parasitic worm ), including those causing onchocerciasis (river blindness) and elephantiasis in humans, as well as heartworms in dogs. Not only are these disease-causing filarial worms infected with Wolbachia , but Wolbachia also seems to play an inordinate role in these diseases. A large part of the pathogenicity of filarial nematodes is due to host immune response toward their Wolbachia . Elimination of Wolbachia from filarial nematodes generally results in either death or sterility of the nematode. Consequently, current strategies for control of filarial nematode diseases include elimination of their symbiotic Wolbachia via the simple doxycycline antibiotic, rather than directly killing the nematode with often more toxic antinematode medications. Naturally existing strains of Wolbachia have been shown to be a route for vector control strategies because of their presence in arthropod populations, such as mosquitoes. Due to the unique traits of Wolbachia that cause cytoplasmic incompatibility , some strains are useful to humans as a promoter of genetic drive within an insect population. Wolbachia -infected females are able to produce offspring with uninfected and infected males; however, uninfected females are only able to produce viable offspring with uninfected males. This gives infected females a reproductive advantage that is greater the higher the frequency of Wolbachia in the population. Computational models predict that introducing Wolbachia strains into natural populations will reduce pathogen transmission and reduce overall disease burden. An example includes a life-shortening Wolbachia that can be used to control dengue virus and malaria by eliminating the older insects that contain more parasites. Promoting the survival and reproduction of younger insects lessens selection pressure for evolution of resistance. In addition, some Wolbachia strains are able to directly reduce viral replication inside the insect. For dengue they include wAllbB and wMelPop with Aedes aegypti , wMel with Aedes albopictus and Aedes aegypti . Wolbachia has also been identified to inhibit replication of chikungunya virus (CHIKV) in A. aegypti . The w Mel strain of Wolbachia pipientis significantly reduced infection and dissemination rates of CHIKV in mosquitoes, compared to Wolbachia uninfected controls and the same phenomenon was observed in yellow fever virus infection converting this bacterium in an excellent promise for YFV and CHIKV suppression. Wolbachia also inhibits the secretion of West Nile virus (WNV) in cell line Aag2 derived from A. aegypti cells. The mechanism is somewhat novel, as the bacteria actually enhances the production of viral genomic RNA in the cell line Wolbachia . Also, the antiviral effect in intrathoracically infected mosquitoes depends on the strain of Wolbachia , and the replication of the virus in orally fed mosquitoes was completely inhibited in wMelPop strain of Wolbachia . The effect of Wolbachia infection on virus replication in insect hosts is complex and depends on the Wolbachia strain and virus species. While several studies have indicated consistent refractory phenotypes of Wolbachia infection on positive-sense RNA viruses in Drosophila melanogaster , the yellow fever mosquito Aedes aegypti and the Asian tiger mosquito Aedes albopictus , this effect is not seen in DNA virus infection and in some cases Wolbachia infection has been associated or shown to increase single stranded DNA and double-stranded DNA virus infection. There is also currently no evidence that Wolbachia infection restricts any tested negative-sense RNA viruses indicating Wolbachia would be unsuitable for restriction of negative-sense RNA arthropod borne viruses. Wolbachia infection can also increase mosquito resistance to malaria, as shown in Anopheles stephensi where the w AlbB strain of Wolbachia hindered the lifecycle of Plasmodium falciparum . However, Wolbachia infections can also enhance pathogen transmission. Wolbachia has enhanced multiple arboviruses in Culex tarsalis mosquitoes. In another study, West Nile Virus (WNV) infection rate was significantly higher in Wolbachia (strain wAlbB)-infected C. tarsalis compared to controls. Wolbachia may induce reactive oxygen species –dependent activation of the Toll (gene family) pathway, which is essential for activation of antimicrobial peptides , defensins , and cecropins that help to inhibit virus proliferation. Conversely, certain strains actually dampen the pathway, leading to higher replication of viruses. One example is with strain wAlbB in Culex tarsalis , where infected mosquitoes actually carried the west nile virus (WNV) more frequently. This is because wAlbB inhibits REL1, an activator of the antiviral Toll immune pathway. As a result, careful studies of the Wolbachia strain and ecological consequences must be done before releasing artificially-infected mosquitoes in the environment. The World Mosquito Program (WMP) uses Wolbachia strain wMel to infect Aedes mosquitos. The mixed-sex mosquitos are intended to infect the local population with wMel, giving them transmission resistance. In 2014, WMP released infected mosquitos in Townsville , an Australia city with 187,000 inhabitants plagued by dengue. For four years after introduction, no cases of dengue were reported. Trials in much smaller areas had been carried out, but a larger area had not been tested. No environmental ill-effects were reported. The cost was A$ 15 per inhabitant, but it was hoped that it could be reduced to US$ 1 in poorer countries with lower labor costs. In 2016, WMP scientist Scott Ritchie proposed using wMel mosquitos to combat the spread of the Zika virus . A study reported that Wolbachia wMel has the ability to block Zika in Brazil. In October 2016, it was announced that US$18 million in funding was being allocated for the use of Wolbachia -infected mosquitoes to fight Zika and dengue viruses. Deployment is slated for early 2017 in Colombia and Brazil. Between 2016 and 2020, WMP conducted its first randomized controlled trial in Yogyakarta , an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist Adi Utarini announced that the trial showed a 77% reduction in dengue cases compared to the control areas. This trial was the "strongest evidence yet" for the technique. In 2017 – 2019, WMP released mosquitos in Niterói, Brazil. In March 2023, Brazil's Oswaldo Cruz Foundation signed an agreement with WMP to provide funds for a large "mosquito factory" producing infected insects. Another method to use Wolbachia in mosquitos exploits the cytoplamic incompatibility between infected males and uninfected females. If an uninfected female mates with an infected male, her eggs become infertile. With enough infected males released, the mosquito population would be reduced temporarily. Verily , the life sciences arm of Google's parent company Alphabet Inc. , uses this method. In July 2017, it announced a plan to release about 20 million Wolbachia -infected male Aedes aegypti mosquitoes in Fresno , California , in an attempt to combat the Zika virus. Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male Wolbachia mosquitoes for Phase 2 of its study to suppress the urban Aedes aegypti mosquito population and fight dengue. On November 3, 2017, the US Environmental Protection Agency (EPA) registered Mosquito Mate, Inc. to release Wolbachia strain "ZAP"-infected male mosquitoes in 20 US states and the District of Columbia. The World Mosquito Program (WMP) uses Wolbachia strain wMel to infect Aedes mosquitos. The mixed-sex mosquitos are intended to infect the local population with wMel, giving them transmission resistance. In 2014, WMP released infected mosquitos in Townsville , an Australia city with 187,000 inhabitants plagued by dengue. For four years after introduction, no cases of dengue were reported. Trials in much smaller areas had been carried out, but a larger area had not been tested. No environmental ill-effects were reported. The cost was A$ 15 per inhabitant, but it was hoped that it could be reduced to US$ 1 in poorer countries with lower labor costs. In 2016, WMP scientist Scott Ritchie proposed using wMel mosquitos to combat the spread of the Zika virus . A study reported that Wolbachia wMel has the ability to block Zika in Brazil. In October 2016, it was announced that US$18 million in funding was being allocated for the use of Wolbachia -infected mosquitoes to fight Zika and dengue viruses. Deployment is slated for early 2017 in Colombia and Brazil. Between 2016 and 2020, WMP conducted its first randomized controlled trial in Yogyakarta , an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist Adi Utarini announced that the trial showed a 77% reduction in dengue cases compared to the control areas. This trial was the "strongest evidence yet" for the technique. In 2017 – 2019, WMP released mosquitos in Niterói, Brazil. In March 2023, Brazil's Oswaldo Cruz Foundation signed an agreement with WMP to provide funds for a large "mosquito factory" producing infected insects. Another method to use Wolbachia in mosquitos exploits the cytoplamic incompatibility between infected males and uninfected females. If an uninfected female mates with an infected male, her eggs become infertile. With enough infected males released, the mosquito population would be reduced temporarily. Verily , the life sciences arm of Google's parent company Alphabet Inc. , uses this method. In July 2017, it announced a plan to release about 20 million Wolbachia -infected male Aedes aegypti mosquitoes in Fresno , California , in an attempt to combat the Zika virus. Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male Wolbachia mosquitoes for Phase 2 of its study to suppress the urban Aedes aegypti mosquito population and fight dengue. On November 3, 2017, the US Environmental Protection Agency (EPA) registered Mosquito Mate, Inc. to release Wolbachia strain "ZAP"-infected male mosquitoes in 20 US states and the District of Columbia. The World Mosquito Program (WMP) uses Wolbachia strain wMel to infect Aedes mosquitos. The mixed-sex mosquitos are intended to infect the local population with wMel, giving them transmission resistance. In 2014, WMP released infected mosquitos in Townsville , an Australia city with 187,000 inhabitants plagued by dengue. For four years after introduction, no cases of dengue were reported. Trials in much smaller areas had been carried out, but a larger area had not been tested. No environmental ill-effects were reported. The cost was A$ 15 per inhabitant, but it was hoped that it could be reduced to US$ 1 in poorer countries with lower labor costs. In 2016, WMP scientist Scott Ritchie proposed using wMel mosquitos to combat the spread of the Zika virus . A study reported that Wolbachia wMel has the ability to block Zika in Brazil. In October 2016, it was announced that US$18 million in funding was being allocated for the use of Wolbachia -infected mosquitoes to fight Zika and dengue viruses. Deployment is slated for early 2017 in Colombia and Brazil. Between 2016 and 2020, WMP conducted its first randomized controlled trial in Yogyakarta , an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist Adi Utarini announced that the trial showed a 77% reduction in dengue cases compared to the control areas. This trial was the "strongest evidence yet" for the technique. In 2017 – 2019, WMP released mosquitos in Niterói, Brazil. In March 2023, Brazil's Oswaldo Cruz Foundation signed an agreement with WMP to provide funds for a large "mosquito factory" producing infected insects. Another method to use Wolbachia in mosquitos exploits the cytoplamic incompatibility between infected males and uninfected females. If an uninfected female mates with an infected male, her eggs become infertile. With enough infected males released, the mosquito population would be reduced temporarily. Verily , the life sciences arm of Google's parent company Alphabet Inc. , uses this method. In July 2017, it announced a plan to release about 20 million Wolbachia -infected male Aedes aegypti mosquitoes in Fresno , California , in an attempt to combat the Zika virus. Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male Wolbachia mosquitoes for Phase 2 of its study to suppress the urban Aedes aegypti mosquito population and fight dengue. On November 3, 2017, the US Environmental Protection Agency (EPA) registered Mosquito Mate, Inc. to release Wolbachia strain "ZAP"-infected male mosquitoes in 20 US states and the District of Columbia.

Wiki

Chikungunya

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

Hepatitis E

Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis . Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A , although the viruses are unrelated. HEV is a positive-sense , single-stranded, nonenveloped, RNA icosahedral virus and one of five known human hepatitis viruses: A, B , C , D , and E. Like hepatitis A, hepatitis E usually follows an acute and self-limiting course of illness (the condition is temporary and the individual recovers) with low death rates in resource-rich areas; however, it can be more severe in pregnant women and people with a weakened immune system , with substantially higher death rates. In pregnant women , especially in the third trimester, the disease is more often severe and is associated with a clinical syndrome called fulminant liver failure , with death rates around 20%. Whereas pregnant women may have a rapid and severe course, organ transplant recipients who receive medications to weaken the immune system and prevent organ rejection can develop a slower and more persistent form called chronic hepatitis E, which is so diagnosed after 3 months of continuous viremia. HEV can be clustered genetically into 8 genotypes, and genotypes 3 and 4 tend to be the ones that cause chronic hepatitis in the immunosuppressed. In 2017, hepatitis E was estimated to affect more than 19 million people. Those most commonly at risk of HEV are men aged 15 to 35 years of age. A preventive vaccine (HEV 239) is approved for use in China . The virus was discovered in 1983 by researchers investigating an outbreak of unexplained hepatitis among Soviet soldiers serving in Afghanistan . The earliest well-documented epidemic of hepatitis E occurred in 1955 in New Delhi and affected tens of thousands of people (hepatitis E virus was identified as the etiological agent at fault retrospectively through testing of stored samples). The average incubation period of hepatitis E is 40 days, ranging from 2 to 8 weeks. After a short prodromal phase symptoms may include jaundice , fatigue, and nausea , though most HEV infections are asymptomatic. The symptomatic phase coincides with elevated hepatic aminotransferase levels. Viral RNA becomes detectable in stool and blood serum during the incubation period. Serum IgM and IgG antibodies against HEV appear just before the onset of clinical symptoms. Recovery leads to virus clearance from the blood, while the virus may persist in stool for much longer. Recovery is also marked by disappearance of IgM antibodies and increase of levels of IgG antibodies. While usually lasting weeks and then resolving, in people with weakened immune systems —particularly in people who have had solid organ transplant—hepatitis E may cause a chronic infection . Occasionally this may result in a life-threatening illness such as fulminant liver failure or liver cirrhosis . Infection with hepatitis E virus can also lead to problems in other organs. For some of these reported conditions such as musculoskeletal or immune-mediated manifestations the relationship is not entirely clear, but for several neurological and blood conditions the relationship appears more consistent: Pregnant women show a more severe course of infection than other populations. Liver failure with mortality rates of 20% to 25% has been reported from outbreaks of genotype 1 and 2 HEV in developing countries. Besides signs of an acute infections, adverse effects on the mother and fetus may include preterm delivery , abortion, stillbirth , and neonatal death. The pathological and biological mechanisms behind the adverse outcomes of pregnancy infections remain largely unclear. Increased viral replication and influence of hormonal changes on the immune system are currently thought to contribute to worsening the course of infection. Furthermore, studies showing evidence for viral replication in the placenta or reporting the full viral life cycle in placental-derived cells in vitro suggest that the human placenta may be a site of viral replication outside the liver. The primary reason for HEV severity in pregnancy remains enigmatic. The average incubation period of hepatitis E is 40 days, ranging from 2 to 8 weeks. After a short prodromal phase symptoms may include jaundice , fatigue, and nausea , though most HEV infections are asymptomatic. The symptomatic phase coincides with elevated hepatic aminotransferase levels. Viral RNA becomes detectable in stool and blood serum during the incubation period. Serum IgM and IgG antibodies against HEV appear just before the onset of clinical symptoms. Recovery leads to virus clearance from the blood, while the virus may persist in stool for much longer. Recovery is also marked by disappearance of IgM antibodies and increase of levels of IgG antibodies. While usually lasting weeks and then resolving, in people with weakened immune systems —particularly in people who have had solid organ transplant—hepatitis E may cause a chronic infection . Occasionally this may result in a life-threatening illness such as fulminant liver failure or liver cirrhosis . Infection with hepatitis E virus can also lead to problems in other organs. For some of these reported conditions such as musculoskeletal or immune-mediated manifestations the relationship is not entirely clear, but for several neurological and blood conditions the relationship appears more consistent: Pregnant women show a more severe course of infection than other populations. Liver failure with mortality rates of 20% to 25% has been reported from outbreaks of genotype 1 and 2 HEV in developing countries. Besides signs of an acute infections, adverse effects on the mother and fetus may include preterm delivery , abortion, stillbirth , and neonatal death. The pathological and biological mechanisms behind the adverse outcomes of pregnancy infections remain largely unclear. Increased viral replication and influence of hormonal changes on the immune system are currently thought to contribute to worsening the course of infection. Furthermore, studies showing evidence for viral replication in the placenta or reporting the full viral life cycle in placental-derived cells in vitro suggest that the human placenta may be a site of viral replication outside the liver. The primary reason for HEV severity in pregnancy remains enigmatic. HEV is classified into the family Hepeviridae , which is divided in two genera, Orthohepevirus (all mammalian and avian HEV isolates) and Piscihepevirus (cutthroat trout HEV). Only one serotype of the human virus is known, and classification is based on the nucleotide sequences of the genome. Genotype 1 can be further subclassified into five subtypes, genotype 2 into two subtypes, and genotypes 3 and 4 have been divided into 10 and seven subtypes. Additionally there are genotypes 5, 6, 7 and 8. Rat HEV was first isolated from Norway rats in Germany, and a 2018 CDC article indicated the detection of rat HEV RNA in a transplant recipient. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs, and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries. Hepatitis E (genotype 1 and, to a lesser extent genotype 2) is endemic and can cause outbreaks in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly by the fecal–oral route due to contamination of water supplies or food; direct person-to-person transmission is uncommon. In contrast to genotypes 1 and 2, genotypes 3 and 4 cause sporadic cases thought to be contracted zoonotically, from direct contact with animals or indirectly from contaminated water or undercooked meat. Outbreaks of epidemic hepatitis E most commonly occur after heavy rainfalls, especially monsoons because of their disruption of water supplies; heavy flooding can causes sewage to contaminate water supplies. : 78 The World Health Organization recommendation for chlorine on HEV inactivation, a free chlorine residual of 0.5 mg/L (6.7 × 10 −5 oz/US gal) for 30 min (pH, <8.0) Major outbreaks have occurred in New Delhi , India (30,000 cases in 1955–1956), Burma (20,000 cases in 1976–1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988). According to Rein et al., HEV genotypes 1 and 2 caused some 20.1 million hepatitis E infections, along with 3.4 million cases of symptomatic disease, and 70,000 deaths in 2005; however the aforementioned paper did not estimate the burden of genotypes 3 and 4. According to the Department for Environment, Food and Rural Affairs, evidence indicated the increase in hepatitis E in the U.K. was due to food-borne zoonoses , citing a study that found in the U.K. that 10% of pork sausages contained the hepatitis E virus. Some research suggests that food must reach a temperature of 70 °C (158 °F) for 20 minutes to eliminate the risk of infection. The Animal Health and Veterinary Laboratories Agency discovered hepatitis E in almost half of all pigs in Scotland. Hepatitis E infection appeared to be more common in people on hemodialysis, although the specific risk factors for transmission are not clear. Hepatitis E due to genotypes other than 1 and 2 is thought to be a zoonosis , in that animals are thought to be the primary reservoir; deer and swine have frequently been implicated. Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Replicative virus has been found in the small intestine , lymph nodes , colon , and liver of experimentally infected pigs . Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are, however, still unclear. Other animal reservoirs are possible but unknown at this time A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat ( Bandicota bengalensis ), the black rat ( Rattus rattus brunneusculus ) and the Asian house shrew ( Suncus murinus ). A new virus designated rat hepatitis E virus has been isolated. HEV has three open reading frames (ORFs) encoding two polyproteins (O1 and O2 protein). ORF2 encodes three capsid proteins whereas O1 encodes seven fragments involved in viral replication, among others. The smallest ORF of the HEV genome, ORF3 is translated from a subgenomic RNA into O3, a protein of 113–115 amino acids. ORF3 is proposed to play critical roles in immune evasion by HEV. Previous studies showed that ORF3 is bound to viral particles found in patient sera and produced in cell culture. Although in cultured cells ORF3 has not appeared essential for HEV RNA replication, viral assembly, or infection, it is required for particle release. The lifecycle of hepatitis E virus is unknown; the capsid protein obtains viral entry by binding to a cellular receptor. ORF2 (c-terminal) moderates viral entry by binding to HSC70 . Geldanamycin blocks the transport of HEV239 capsid protein, but not the binding/entry of the truncated capsid protein, which indicates that Hsp90 plays an important part in HEV transport. HEV is classified into the family Hepeviridae , which is divided in two genera, Orthohepevirus (all mammalian and avian HEV isolates) and Piscihepevirus (cutthroat trout HEV). Only one serotype of the human virus is known, and classification is based on the nucleotide sequences of the genome. Genotype 1 can be further subclassified into five subtypes, genotype 2 into two subtypes, and genotypes 3 and 4 have been divided into 10 and seven subtypes. Additionally there are genotypes 5, 6, 7 and 8. Rat HEV was first isolated from Norway rats in Germany, and a 2018 CDC article indicated the detection of rat HEV RNA in a transplant recipient. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs, and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs, and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries. Hepatitis E (genotype 1 and, to a lesser extent genotype 2) is endemic and can cause outbreaks in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly by the fecal–oral route due to contamination of water supplies or food; direct person-to-person transmission is uncommon. In contrast to genotypes 1 and 2, genotypes 3 and 4 cause sporadic cases thought to be contracted zoonotically, from direct contact with animals or indirectly from contaminated water or undercooked meat. Outbreaks of epidemic hepatitis E most commonly occur after heavy rainfalls, especially monsoons because of their disruption of water supplies; heavy flooding can causes sewage to contaminate water supplies. : 78 The World Health Organization recommendation for chlorine on HEV inactivation, a free chlorine residual of 0.5 mg/L (6.7 × 10 −5 oz/US gal) for 30 min (pH, <8.0) Major outbreaks have occurred in New Delhi , India (30,000 cases in 1955–1956), Burma (20,000 cases in 1976–1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988). According to Rein et al., HEV genotypes 1 and 2 caused some 20.1 million hepatitis E infections, along with 3.4 million cases of symptomatic disease, and 70,000 deaths in 2005; however the aforementioned paper did not estimate the burden of genotypes 3 and 4. According to the Department for Environment, Food and Rural Affairs, evidence indicated the increase in hepatitis E in the U.K. was due to food-borne zoonoses , citing a study that found in the U.K. that 10% of pork sausages contained the hepatitis E virus. Some research suggests that food must reach a temperature of 70 °C (158 °F) for 20 minutes to eliminate the risk of infection. The Animal Health and Veterinary Laboratories Agency discovered hepatitis E in almost half of all pigs in Scotland. Hepatitis E infection appeared to be more common in people on hemodialysis, although the specific risk factors for transmission are not clear. Hepatitis E due to genotypes other than 1 and 2 is thought to be a zoonosis , in that animals are thought to be the primary reservoir; deer and swine have frequently been implicated. Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Replicative virus has been found in the small intestine , lymph nodes , colon , and liver of experimentally infected pigs . Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are, however, still unclear. Other animal reservoirs are possible but unknown at this time A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat ( Bandicota bengalensis ), the black rat ( Rattus rattus brunneusculus ) and the Asian house shrew ( Suncus murinus ). A new virus designated rat hepatitis E virus has been isolated. HEV has three open reading frames (ORFs) encoding two polyproteins (O1 and O2 protein). ORF2 encodes three capsid proteins whereas O1 encodes seven fragments involved in viral replication, among others. The smallest ORF of the HEV genome, ORF3 is translated from a subgenomic RNA into O3, a protein of 113–115 amino acids. ORF3 is proposed to play critical roles in immune evasion by HEV. Previous studies showed that ORF3 is bound to viral particles found in patient sera and produced in cell culture. Although in cultured cells ORF3 has not appeared essential for HEV RNA replication, viral assembly, or infection, it is required for particle release. The lifecycle of hepatitis E virus is unknown; the capsid protein obtains viral entry by binding to a cellular receptor. ORF2 (c-terminal) moderates viral entry by binding to HSC70 . Geldanamycin blocks the transport of HEV239 capsid protein, but not the binding/entry of the truncated capsid protein, which indicates that Hsp90 plays an important part in HEV transport. In terms of the diagnosis of hepatitis E, only a laboratory blood test that confirms the presence of HEV RNA or IgM antibodies to HEV can be trusted. In the United States no serologic tests for diagnosis of HEV infection have ever been authorized by the Food and Drug Administration . The World Health Organization has developed an international standard strain for detection and quantification of HEV RNA. In acute infection the viremic window for detection of HEV RNA closes 3 weeks after symptoms begin. Assuming that vaccination has not occurred, tests may show: if the person's immune system is normal , then if IgM anti-HEV is negative, then there is no evidence of recent HEV infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection if the person's immune system is weakened by disease or medical treatment , as in the case of a person who has received a solid organ transplant, then if IgM anti-HEV is negative, then if additional blood testing reveals positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection, and HEV RNA may be useful to track resolution if IgM anti-HEV is negative, then there is no evidence of recent HEV infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection if IgM anti-HEV is negative, then if additional blood testing reveals positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection, and HEV RNA may be useful to track resolution positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infectionAssuming that vaccination has not occurred, tests may show: if the person's immune system is normal , then if IgM anti-HEV is negative, then there is no evidence of recent HEV infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection if the person's immune system is weakened by disease or medical treatment , as in the case of a person who has received a solid organ transplant, then if IgM anti-HEV is negative, then if additional blood testing reveals positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection, and HEV RNA may be useful to track resolution if IgM anti-HEV is negative, then there is no evidence of recent HEV infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection if IgM anti-HEV is negative, then if additional blood testing reveals positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infection if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection, and HEV RNA may be useful to track resolution positive HEV RNA then the person has HEV infection negative HEV RNA then there is no evidence of current or recent infectionSanitation is the most important measure in prevention of hepatitis E; this consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures, and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many other diseases that plague developing nations. Cooking meat at 71 °C (159.8 °F) for five minutes kills the hepatitis E virus, different temperatures means different time to inactivate the virus. The amount of virus present in blood products required to cause transfusion-transmitted infection (TTI) appears variable. Transfusion transmission of hepatitis E virus can be screened via minipool HEV NAT (Nucleic acid testing) screening. NAT is a technique used to screen blood molecularly, when blood donations are received; it screens for TTI. A vaccine based on recombinant viral proteins was developed in the 1990s and tested in a high-risk population (in Nepal ) in 2001. The vaccine appeared to be effective and safe, but development was stopped for lack of profitability, since hepatitis E is rare in developed countries. No hepatitis E vaccine is licensed for use in the United States. The exception is China; after more than a year of scrutiny and inspection by China's State Food and Drug Administration (SFDA), a hepatitis E vaccine developed by Chinese scientists was available at the end of 2012. The vaccine—called HEV 239 by its developer Xiamen Innovax Biotech —was approved for prevention of hepatitis E in 2012 by the Chinese Ministry of Science and Technology, following a controlled trial on 100,000+ people from Jiangsu Province where none of those vaccinated became infected during a 12-month period, compared to 15 in the group given placebo. The first vaccine batches came out of Innovax's factory in late October 2012, to be sold to Chinese distributors. Due to lack of evidence, the World Health Organization has not made a recommendation regarding routine use of the HEV 239 vaccine as of 2015. Its 2015 position was that national authorities may decide to use the vaccine based on their local epidemiology. Sanitation is the most important measure in prevention of hepatitis E; this consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures, and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many other diseases that plague developing nations. Cooking meat at 71 °C (159.8 °F) for five minutes kills the hepatitis E virus, different temperatures means different time to inactivate the virus. The amount of virus present in blood products required to cause transfusion-transmitted infection (TTI) appears variable. Transfusion transmission of hepatitis E virus can be screened via minipool HEV NAT (Nucleic acid testing) screening. NAT is a technique used to screen blood molecularly, when blood donations are received; it screens for TTI. A vaccine based on recombinant viral proteins was developed in the 1990s and tested in a high-risk population (in Nepal ) in 2001. The vaccine appeared to be effective and safe, but development was stopped for lack of profitability, since hepatitis E is rare in developed countries. No hepatitis E vaccine is licensed for use in the United States. The exception is China; after more than a year of scrutiny and inspection by China's State Food and Drug Administration (SFDA), a hepatitis E vaccine developed by Chinese scientists was available at the end of 2012. The vaccine—called HEV 239 by its developer Xiamen Innovax Biotech —was approved for prevention of hepatitis E in 2012 by the Chinese Ministry of Science and Technology, following a controlled trial on 100,000+ people from Jiangsu Province where none of those vaccinated became infected during a 12-month period, compared to 15 in the group given placebo. The first vaccine batches came out of Innovax's factory in late October 2012, to be sold to Chinese distributors. Due to lack of evidence, the World Health Organization has not made a recommendation regarding routine use of the HEV 239 vaccine as of 2015. Its 2015 position was that national authorities may decide to use the vaccine based on their local epidemiology. There is no drug that has established safety and effectiveness for hepatitis E, and there have been no large randomized clinical trials of antiviral drugs. Reviews of existing small studies suggest that ribavirin can be considered effective in immunocompromised people who have developed chronic infection. Chronic HEV infection is associated with immunosuppressive therapies, and when that happens in individuals with solid- organ transplantation , reducing immunosuppressive medications can result in clearance of HEV in one third of patients. The hepatitis E virus causes around 20 million infections a year. These result in around three million acute illnesses and resulted in 44,000 deaths during 2015. Pregnant women are particularly at risk of complications due to HEV infection, who can develop an acute form of the disease that is fatal in 30% of cases or more. HEV is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Hepatitis E is endemic in Central Asia, while Central America and the Middle East have reported outbreaks. Increasingly, hepatitis E is being seen in developed nations, with reports in 2015 of 848 cases of hepatitis E virus infection in England and Wales. In October 2007, an epidemic of hepatitis E occurred in Kitgum District of northern Uganda. This outbreak progressed to become one of the largest known hepatitis E outbreaks in the world. By June 2009, it had resulted in illness in 10,196 persons and 160 deaths. The aforementioned outbreak occurred despite no previous epidemics having been documented in the country, women were the most affected by HEV. In July 2012, an outbreak was reported in South Sudanese refugee camps in Maban County near the Sudan border. South Sudan 's Ministry of Health reported over 400 cases and 16 fatalities as of 13 September 2012. Progressing further, as of 2 February 2013, 88 died due to the outbreak. The medical charity Medecins Sans Frontieres said it treated almost 4000 people. In April 2014, an outbreak in the Biratnagar Municipality of Nepal resulted in infection of over 6000 locals and at least 9 dead. During an outbreak in Namibia , the number of affected people rose from 490 in January 2018, to 5014 (with 42 deaths) by April 2019, to 6151 cases (with 56 deaths) by August 2019; the WHO estimated that the case fatality rate was 0.9%. In Hong Kong in May 2020, there were at least 10 cases of hepatitis E that were transmitted by rats, and possibly hundreds of cases that had a transmission mechanism that is not fully understood. 2024 outbreak in Finland . A record number of hepatitis E cases have been diagnosed in Finland so far this year, according to figures released on Tuesday by public health authority THL. Data from the authority's Infectious Diseases Register showed that a total of 92 lab-confirmed infections have been recorded since the beginning of January until 12 March, with 42 people requiring hospital treatment. The outbreak has been suspected to be caused by a batch of mettwurst that has been recalled. In October 2007, an epidemic of hepatitis E occurred in Kitgum District of northern Uganda. This outbreak progressed to become one of the largest known hepatitis E outbreaks in the world. By June 2009, it had resulted in illness in 10,196 persons and 160 deaths. The aforementioned outbreak occurred despite no previous epidemics having been documented in the country, women were the most affected by HEV. In July 2012, an outbreak was reported in South Sudanese refugee camps in Maban County near the Sudan border. South Sudan 's Ministry of Health reported over 400 cases and 16 fatalities as of 13 September 2012. Progressing further, as of 2 February 2013, 88 died due to the outbreak. The medical charity Medecins Sans Frontieres said it treated almost 4000 people. In April 2014, an outbreak in the Biratnagar Municipality of Nepal resulted in infection of over 6000 locals and at least 9 dead. During an outbreak in Namibia , the number of affected people rose from 490 in January 2018, to 5014 (with 42 deaths) by April 2019, to 6151 cases (with 56 deaths) by August 2019; the WHO estimated that the case fatality rate was 0.9%. In Hong Kong in May 2020, there were at least 10 cases of hepatitis E that were transmitted by rats, and possibly hundreds of cases that had a transmission mechanism that is not fully understood. 2024 outbreak in Finland . A record number of hepatitis E cases have been diagnosed in Finland so far this year, according to figures released on Tuesday by public health authority THL. Data from the authority's Infectious Diseases Register showed that a total of 92 lab-confirmed infections have been recorded since the beginning of January until 12 March, with 42 people requiring hospital treatment. The outbreak has been suspected to be caused by a batch of mettwurst that has been recalled. The strains of HEV that exist today may have arisen from a shared ancestor virus 536 to 1344 years ago. Another analysis has dated the origin of Hepatitis E to ~6000 years ago, with a suggestion that this was associated with domestication of pigs. At some point, two clades may have diverged — an anthropotropic form and an enzootic form — which subsequently evolved into genotypes 1 and 2 and genotypes 3 and 4, respectively. Whereas genotype 2 remains less commonly detected than other genotypes, genetic evolutionary analyses suggest that genotypes 1, 3, and 4 have spread substantially during the past 100 years.

Wiki

Chikungunya

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

Neglected tropical diseases in India

Neglected tropical diseases in India are a group of bacterial, parasitic, viral, and fungal infections that are common in low income countries but receive little funding to address them. Neglected tropical diseases are common in India. India's population is about 1.3 billion as of 2018, which is the second largest in the world. However, high population does not explain the greater frequently of neglected tropical diseases in India than in other countries. Neglected tropical diseases in India occur in areas of both urban and rural poverty. The neglected tropical diseases which especially affect India include ascariasis , hookworm infection , trichuriasis , dengue fever , lymphatic filariasis , trachoma , melioidosis , cysticercosis , leprosy , echinococcosis , visceral leishmaniasis , and rabies . Various organizations will include different diseases under the umbrella term of "neglected tropical diseases," but most diseases listed as such occur in tropical climates , lack global public attention, and have high infection rates. [ citation needed ] The World Health Organization recognizes 20 neglected tropical diseases, of which 12 are present in India.India has a goal for the elimination of kala-azar. The steps to eliminating the disease include passive and active case detection, early diagnosis and treatment, and vector control integrated into medical treatment. Before the year 2000 there was hope and expectation that India could eliminate kala-azar from the country. In those years there were various programs to continue usual treatments and develop new ones. Around year 2000 there were reports that parasites which cause kala-azar had developed drug resistance to pentavalent antimonial , which was the popular drug for treating this disease for the last 50 years. The disease spread to become a problem again and now more difficult to treat. In poorer areas of India underreporting of the disease was a problem, allowing the disease to spread. The newer treatments of that time were expensive. The treatment of kala-azar in India since about year 2000 has been difficult. In 2017 the Indian government had contained kala-azar in certain regions with the goal of providing easy access to medical treatment to eliminate it from the country. The intent was that by 2020 the disease should be very uncommon and also should never spread or grow again. Physicians use a drug to treat kala-azar both before and after the patient seems cured, but take care to use a safe amount. The work that health agencies in India have done to reduce kala-azar are learning models for India or any other country to apply to other public health programs to eliminate infectious disease. African trypanosomiasis (sleeping sickness) is not a problem in India. Researchers do monitor watching for the disease. In 2005, an Indian farmer became ill following an unusual infection with an Indian species of this parasite called Trypanosoma evansi . Chagas disease is not a problem in India. Chagas disease, like African trypanosomiasis, has a Trypanosoma parasite as its cause. This parasite is not in India. India has a goal for the elimination of kala-azar. The steps to eliminating the disease include passive and active case detection, early diagnosis and treatment, and vector control integrated into medical treatment. Before the year 2000 there was hope and expectation that India could eliminate kala-azar from the country. In those years there were various programs to continue usual treatments and develop new ones. Around year 2000 there were reports that parasites which cause kala-azar had developed drug resistance to pentavalent antimonial , which was the popular drug for treating this disease for the last 50 years. The disease spread to become a problem again and now more difficult to treat. In poorer areas of India underreporting of the disease was a problem, allowing the disease to spread. The newer treatments of that time were expensive. The treatment of kala-azar in India since about year 2000 has been difficult. In 2017 the Indian government had contained kala-azar in certain regions with the goal of providing easy access to medical treatment to eliminate it from the country. The intent was that by 2020 the disease should be very uncommon and also should never spread or grow again. Physicians use a drug to treat kala-azar both before and after the patient seems cured, but take care to use a safe amount. The work that health agencies in India have done to reduce kala-azar are learning models for India or any other country to apply to other public health programs to eliminate infectious disease. African trypanosomiasis (sleeping sickness) is not a problem in India. Researchers do monitor watching for the disease. In 2005, an Indian farmer became ill following an unusual infection with an Indian species of this parasite called Trypanosoma evansi . Chagas disease is not a problem in India. Chagas disease, like African trypanosomiasis, has a Trypanosoma parasite as its cause. This parasite is not in India. Soil-transmitted helminthiasis is a group of various parasitic diseases which different roundworms cause. The large roundworm causes Ascariasis , the hookworm causes Hookworm infection , and the whipworm causes Trichuriasis . These worms are related and there are strategies for prevention which apply to all of them. The World Health Organization estimated that in 2015, 75% of the children in India who had Soil-transmitted helminthiasis also got treatment. India has 40% of the world's lymphatic filariasis (LF) cases. For the patient, one of the major costs of treating the disease is having to take a lot of time off work. A year 2000 survey reported that about half of the people in India were at risk of contracting LF. Men and women can get this disease equally, but in the past, there have been barriers to women accessing treatment in the normal way. In 1955 the Indian government established the National Filaria Control Programme to reduce LF. In 1997 India joined a World Health Assembly resolution to eliminate LF by 2020. In India to achieve this goal healthcare must be very accessible to almost everyone at risk for the disease. In 2015 the Indian government launched a health campaign called Hathipaon Mukt Bharat (Filaria Free India) to encourage public participation in eliminating LF. Following some missed deadlines in 2015 and before a 2020 target date for eliminating LF, various media outlets discussed how India might meet the goal or what it should happen next if more time is required. The Ayurvedic text Sushruta Samhita described lymphatic filariasis. Echinococcosis is a parasitic disease of tapeworms . Taeniasis and cysticercosis are both parasitic diseases caused by tapeworms in the family Taeniidae . [ citation needed ] Guinea-worm disease was a neglected tropical disease in India until 2000 when it was eradicated. In 2006 India announced the eradication of yaws after going since 2003 with no reported cases of the disease. Foodborne trematode infection is not a problem in India. [ citation needed ] From 1969 to 2012 there have only been a few reports of a few people in India getting fasciolosis (foodborne trematode infection). The disease is endemic among cows, buffalo, sheep, and goats in India. A 2012 paper which reported two human infections urged for attention that human infection might be more prevalent. Onchocerciasis (river blindness) is not a problem in India. [ citation needed ] Onchocerciasis has been found in India in an unusual case. Schistosomiasis is not a problem in India. A 2015 report described that while India has no routine reports of schistosomiasis , the disease might be present and unreported. A 1952 paper described the disease present in an Indian village and how WHO investigators treated the disease and tried to identify its source. In retrospect, that older paper was unusual, and either this disease is uncommon in India or difficult to detect. Soil-transmitted helminthiasis is a group of various parasitic diseases which different roundworms cause. The large roundworm causes Ascariasis , the hookworm causes Hookworm infection , and the whipworm causes Trichuriasis . These worms are related and there are strategies for prevention which apply to all of them. The World Health Organization estimated that in 2015, 75% of the children in India who had Soil-transmitted helminthiasis also got treatment. India has 40% of the world's lymphatic filariasis (LF) cases. For the patient, one of the major costs of treating the disease is having to take a lot of time off work. A year 2000 survey reported that about half of the people in India were at risk of contracting LF. Men and women can get this disease equally, but in the past, there have been barriers to women accessing treatment in the normal way. In 1955 the Indian government established the National Filaria Control Programme to reduce LF. In 1997 India joined a World Health Assembly resolution to eliminate LF by 2020. In India to achieve this goal healthcare must be very accessible to almost everyone at risk for the disease. In 2015 the Indian government launched a health campaign called Hathipaon Mukt Bharat (Filaria Free India) to encourage public participation in eliminating LF. Following some missed deadlines in 2015 and before a 2020 target date for eliminating LF, various media outlets discussed how India might meet the goal or what it should happen next if more time is required. The Ayurvedic text Sushruta Samhita described lymphatic filariasis. Echinococcosis is a parasitic disease of tapeworms . Taeniasis and cysticercosis are both parasitic diseases caused by tapeworms in the family Taeniidae . [ citation needed ]Guinea-worm disease was a neglected tropical disease in India until 2000 when it was eradicated. In 2006 India announced the eradication of yaws after going since 2003 with no reported cases of the disease. Foodborne trematode infection is not a problem in India. [ citation needed ] From 1969 to 2012 there have only been a few reports of a few people in India getting fasciolosis (foodborne trematode infection). The disease is endemic among cows, buffalo, sheep, and goats in India. A 2012 paper which reported two human infections urged for attention that human infection might be more prevalent. Onchocerciasis (river blindness) is not a problem in India. [ citation needed ] Onchocerciasis has been found in India in an unusual case. Schistosomiasis is not a problem in India. A 2015 report described that while India has no routine reports of schistosomiasis , the disease might be present and unreported. A 1952 paper described the disease present in an Indian village and how WHO investigators treated the disease and tried to identify its source. In retrospect, that older paper was unusual, and either this disease is uncommon in India or difficult to detect. Mycetoma is an infection under the skin which in India may have either a fungus or a bacterium as cause. In Rajasthan the cause is usually a fungus, but elsewhere in India a bacterium usually causes the disease. Small health surveys have shown that mycetoma is common in central India. The disease is difficult to treat. The treatment for fungus will not work on the bacteria and vice versa. When it is a bacterium the treatment period is long. In 1874 Henry Vandyke Carter , a British surgeon, wrote a book titled On mycetoma, or the fungus disease of India . Mycetoma is an infection under the skin which in India may have either a fungus or a bacterium as cause. In Rajasthan the cause is usually a fungus, but elsewhere in India a bacterium usually causes the disease. Small health surveys have shown that mycetoma is common in central India. The disease is difficult to treat. The treatment for fungus will not work on the bacteria and vice versa. When it is a bacterium the treatment period is long. In 1874 Henry Vandyke Carter , a British surgeon, wrote a book titled On mycetoma, or the fungus disease of India . From 1983 until 2005 India organized successful programs to eliminate leprosy as a public health problem. While these programs reduced the number of people in India with leprosy from 58 in 10,000 to 1 in 10,000, they did not eliminate leprosy entirely. Completely eliminating the disease is possible in the near future. The National Leprosy Eradication Program is part of the government solution to ending the disease. [ citation needed ] Without health intervention, it is possible that leprosy rates could rise and all the progress could be lost. A 2018 study reported that India does well at detecting leprosy in poor areas, but more often misses cases in places with more money. A 2019 report described how newly available technology should make detecting and treating leprosy in India more easy. In December 2017 the health minister of India announced that India was free of trachoma . This announcement included a statement that there were no children in India who had an active case of trachoma. A 2011 paper had speculated that India could eliminate trachoma within 10 years. The Indian government began programs to eliminate yaws in the 1950s. India began its Yaws Eradication Program in 1996 and identified 735 cases at its start. In 2004 the Indian government announced that the health program seemed to have eliminated the disease. Even after yaws seemed to be gone, the government continued monitoring and searching for cases heavily through 2006. Following that, there was a program to investigate rumors of yaws through 2011. In May 2016 the World Health Organization declared India free of yaws. India was the first country where yaws was endemic and which eliminated it. This success in India led to excite for other countries to also try to eliminate yaws by year 2020 using techniques which India developed. Buruli ulcer is not a problem in India. [ citation needed ] In 2019 physicians identified a case of Buruli ulcer in India, but the patient was from Nigeria where the disease is present. From 1983 until 2005 India organized successful programs to eliminate leprosy as a public health problem. While these programs reduced the number of people in India with leprosy from 58 in 10,000 to 1 in 10,000, they did not eliminate leprosy entirely. Completely eliminating the disease is possible in the near future. The National Leprosy Eradication Program is part of the government solution to ending the disease. [ citation needed ] Without health intervention, it is possible that leprosy rates could rise and all the progress could be lost. A 2018 study reported that India does well at detecting leprosy in poor areas, but more often misses cases in places with more money. A 2019 report described how newly available technology should make detecting and treating leprosy in India more easy. In December 2017 the health minister of India announced that India was free of trachoma . This announcement included a statement that there were no children in India who had an active case of trachoma. A 2011 paper had speculated that India could eliminate trachoma within 10 years. The Indian government began programs to eliminate yaws in the 1950s. India began its Yaws Eradication Program in 1996 and identified 735 cases at its start. In 2004 the Indian government announced that the health program seemed to have eliminated the disease. Even after yaws seemed to be gone, the government continued monitoring and searching for cases heavily through 2006. Following that, there was a program to investigate rumors of yaws through 2011. In May 2016 the World Health Organization declared India free of yaws. India was the first country where yaws was endemic and which eliminated it. This success in India led to excite for other countries to also try to eliminate yaws by year 2020 using techniques which India developed. Buruli ulcer is not a problem in India. [ citation needed ] In 2019 physicians identified a case of Buruli ulcer in India, but the patient was from Nigeria where the disease is present. The WHO groups dengue and chikungunya fever together, but these are separate conditions. [ citation needed ] India had chikungunya cases before 1973 when the disease was nearly eliminated. In 2005 India got another case of this. Checkungunya cases are rising in India Rabies has been a problem in India since ancient times. Rabies often comes from dog bites . In India there are many stray dogs and many people report being bitten by them. To determine whether someone requires treatment for rabies or only treatment for the bite, the physician should have information about the incidence of rabies in animals in the area. In India about 2% of people who are bitten get a rabies vaccine . A 2012 paper argued that there was now enough information about rabies in India to plan to contain and prevent the disease nationally. For people in India who get rabies the death rate is nearly 100%. The WHO groups dengue and chikungunya fever together, but these are separate conditions. [ citation needed ] India had chikungunya cases before 1973 when the disease was nearly eliminated. In 2005 India got another case of this. Checkungunya cases are rising in India Rabies has been a problem in India since ancient times. Rabies often comes from dog bites . In India there are many stray dogs and many people report being bitten by them. To determine whether someone requires treatment for rabies or only treatment for the bite, the physician should have information about the incidence of rabies in animals in the area. In India about 2% of people who are bitten get a rabies vaccine . A 2012 paper argued that there was now enough information about rabies in India to plan to contain and prevent the disease nationally. For people in India who get rabies the death rate is nearly 100%. Incidence of scabies in India ranges from 13 to 59% throughout observed areas. Little research exists on how much this condition affects Indian people's work, leisure, and sleep. Various epidemiological studies exist reporting the number of people in India with scabies in various times and places. Topical Permethrin and oral ivermectin are commonly available in India for treatment. The envenomation is the danger of the snakebite, and not the bite itself. The four snakes in India which account for most bites are the Indian cobra , common krait , Russell's viper , and saw-scaled viper . Besides these four there are various other snakes which bite enough to require an organized medical response. In May 2018 the World Health Organization declared that responding to snake bites is a global health priority. Some places in India use traditional folk medicine with plants to treat snakebite. Designing antivenom is a challenge because different snakes require different antivenom to treat, and there are many types of snakes in India. 97% of snake bites occur in rural areas. Snakes have a special place in Indian society and culture. Because of this, many people who receive a snakebite treat their illness with less medical urgency than they would some other disease. A 2010 review of snake bite in India found that there is underreporting of the problem and also insufficient health care treatment available. A 1954 study tracked snake bites since 1940. This study estimated 300,000-400,000 bites a year with 10% of those being deadly. Treatment which should be available but which are sometimes hard to get includes a whole blood clotting test and a venom detection kit . Incidence of scabies in India ranges from 13 to 59% throughout observed areas. Little research exists on how much this condition affects Indian people's work, leisure, and sleep. Various epidemiological studies exist reporting the number of people in India with scabies in various times and places. Topical Permethrin and oral ivermectin are commonly available in India for treatment. The envenomation is the danger of the snakebite, and not the bite itself. The four snakes in India which account for most bites are the Indian cobra , common krait , Russell's viper , and saw-scaled viper . Besides these four there are various other snakes which bite enough to require an organized medical response. In May 2018 the World Health Organization declared that responding to snake bites is a global health priority. Some places in India use traditional folk medicine with plants to treat snakebite. Designing antivenom is a challenge because different snakes require different antivenom to treat, and there are many types of snakes in India. 97% of snake bites occur in rural areas. Snakes have a special place in Indian society and culture. Because of this, many people who receive a snakebite treat their illness with less medical urgency than they would some other disease. A 2010 review of snake bite in India found that there is underreporting of the problem and also insufficient health care treatment available. A 1954 study tracked snake bites since 1940. This study estimated 300,000-400,000 bites a year with 10% of those being deadly. Treatment which should be available but which are sometimes hard to get includes a whole blood clotting test and a venom detection kit . India and South Asia have about half of the world's cases of kala azar, lymphatic filariasis, and leprosy. The region also has about a third of rabies deaths and a quarter of the South Asia, in addition to one-third of the rabies deaths, one-quarter of the intestinal helminth infections. As of 2014 there was not good information about dengue and Japanese encephalitis , but these diseases are a major burden in India also. Of the 17 neglected tropical diseases which the World Health Organization recognized in 2017, six are common in India. Those 6 diseases are Lymphatic filariasis , kala-azar ( Visceral leishmaniasis ), Leptospirosis , Rabies , Soil-transmitted helminthiasis , and Dengue fever . The Global Burden of Disease Study is a regularly updated report which attempts to describe the extent to which each major disease in the world affects individuals with those diseases. This report identifies surprising problems and described them to be unknown among many health professionals. One surprising finding of the 2016 Global Burden of Disease study is that India has the most and worst cases of 11 of the 16 neglected tropical diseases it considered. India has the most cases of all neglected tropical diseases which occur in India. Elimination of as many of these diseases as possible is a goal. The government of India collaborates with the World Health Organization in making financial investments in health care for the purpose of reducing and eliminating neglected tropical diseases in India. In 2005, the Indian Health Ministry , Bangladeshi Health Ministry , and the Nepali Health Ministry shared a memorandum of understanding to eliminate kala-azar in their shared region by 2015. A 2015 study reported that India's public health programs were reducing leprosy rates but not quickly enough to eliminate the disease from the region. In 2017 the Indian government began participating in the World Health Organization's plan to eliminate 10 of the neglected tropical diseases. The government strategy was to reduce poverty, promote sanitation, do vector control , and provide public health education. The neglected tropical diseases are diseases of poverty and poverty reduction in society will reduce them. [ citation needed ] Some people feel embarrassed to have a disease, but a disease is not anyone's fault. The government of India sometimes has organized health campaigns to teach about diseases so that people feel comfortable coming for medical help when they need it.

Wiki

Chikungunya

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

Disease Vector Education Center

The Disease Vector Education Center is located in St. Augustine, Florida . It is commonly called the Mosquito Museum by locals and is the first museum of its kind in the United States . It features an insect themed playground, a simulated helicopter, and resources to learn about malaria , dengue fever , West Nile virus , yellow fever , Zika virus , chikungunya , and lymphatic filariasis . The education center opened in 2024 and is operated by the Anastasia Mosquito Control District, which is a special district funded by the taxpayers of St. Johns County, Florida . It cost $4.5 million to build and is 6,000 square feet. The University of Florida and Florida Department of Agriculture and Consumer Services contributed resources to the center.

Wiki

Chikungunya

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

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 .

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Orf_(disease)/html

Orf (disease)

Orf is a farmyard pox , a type of zoonosis . It causes small pustules in the skin of primarily sheep and goats , but can also occur on the hands of humans. A pale halo forms around a red centre. It may persist for several weeks before crusting and then either resolves or leaves a hard lump . There is usually only one lesion, but there may be many, and they are not painful. Sometimes there are swollen lymph glands . It is caused by a Parapoxvirus . It can occur in humans who handle infected animals or contaminated objects. One third of cases may develop erythema multiforme . Once resolved, a person can still be infected again. Generally, treatment options are limited. Injecting the lesion with cidofovir or applying imiquimod has been tried. It is sometimes necessary to cut them out . The vaccine used in sheep to prevent orf is live and has been known to cause disease in humans. The disease is endemic in livestock herds worldwide. A recent outbreak emerged in southwest Ethiopia between October 2019 and May 2020. Orf is a zoonotic disease , meaning humans can contract this disorder through direct contact with infected sheep and goats or with fomites carrying the orf virus. It causes a purulent -appearing papule locally and generally no systemic symptoms. Infected locations can include the finger, hand, arm, face and even the penis (caused by infection either from contact with the hand during urination or from bestiality ). Consequently, it is important to observe good personal hygiene and to wear gloves when treating infected animals. It may appear similar to cowpox and pseudocowpox . While orf is usually a benign self-limiting illness which resolves in 3-6 weeks, in the immunocompromised it can be very progressive and even life-threatening. One percent topical cidofovir has been successfully used in a few patients with progressive disease. Serious damage may be inflicted on the eye if it is infected by orf, even among healthy individuals. The virus can survive in the soil for at least six months. Orf is primarily a disease of sheep and goats although it has been reported as a natural disease in humans , steenbok and alpacas , chamois and tahrs , reindeer , musk oxen , dogs , cats , mountain goats , bighorn sheep , dall sheep , and red squirrels . It has been recorded since the late 19th century and has been reported from most sheep-or goat-raising areas, including those in Europe, the Middle East, the United States, Africa, Asia, South America, Canada, New Zealand and Australia. Orf is spread by fomites and direct contact. In some environments, infection is injected by scratches from thistles of both growing and felled plants. Symptoms include papules and pustules on the lips and muzzle, and less commonly in the mouth of young lambs and on the eyelids, feet, and teats of ewes. The lesions progress to thick crusts which may bleed. Orf in the mouths of lambs may prevent suckling and cause weight loss, and can infect the udder of the mother ewe, thus potentially leading to mastitis . Sheep are prone to reinfection. Occasionally the infection can be extensive and persistent if the animal does not produce an immune response. A live virus vaccine ( ATCvet code: QI04AD01 ( WHO ) ) is made from scab material and usually given to ewes at the age of two months, but only to lambs when there is an outbreak. The vaccine can cause disease in humans. In sheep and goats, the lesions mostly appear on or near the hairline and elsewhere on the lips and muzzle. In some cases the lesions appear on and in the nostrils, around the eyes, on the thigh, coronet, vulva , udder, and axilla . In rare cases, mostly involving young lambs, lesions are found on the tongue, gums, roof of the mouth and the oesophagus. It has also been reported a number of times to cause lesions in the rumen. In one case it was shown that a severe form of orf virus caused an outbreak involving the gastrointestinal tract, lungs, heart, as well as the buccal cavity, cheeks, tongue and lips. Another severe case was reported pharyngitis, genital lesions and infection of the hooves which led to lameness and, in some cases, sloughing of the hoof. More typically, sheep will become free of orf within a week or so as the disease runs its course. Sheep custodians can assist by ensuring infected lambs receive sufficient milk and separating out the infected stock to slow down cross-transmission to healthy animals. It is advisable for those handling infected animals to wear disposable gloves to prevent cross infection and self-infection. A veterinarian must be contacted if there is a risk of misdiagnosis with other, more serious conditions. It has been recorded since the late 19th century and has been reported from most sheep-or goat-raising areas, including those in Europe, the Middle East, the United States, Africa, Asia, South America, Canada, New Zealand and Australia. Orf is spread by fomites and direct contact. In some environments, infection is injected by scratches from thistles of both growing and felled plants. Symptoms include papules and pustules on the lips and muzzle, and less commonly in the mouth of young lambs and on the eyelids, feet, and teats of ewes. The lesions progress to thick crusts which may bleed. Orf in the mouths of lambs may prevent suckling and cause weight loss, and can infect the udder of the mother ewe, thus potentially leading to mastitis . Sheep are prone to reinfection. Occasionally the infection can be extensive and persistent if the animal does not produce an immune response. A live virus vaccine ( ATCvet code: QI04AD01 ( WHO ) ) is made from scab material and usually given to ewes at the age of two months, but only to lambs when there is an outbreak. The vaccine can cause disease in humans. In sheep and goats, the lesions mostly appear on or near the hairline and elsewhere on the lips and muzzle. In some cases the lesions appear on and in the nostrils, around the eyes, on the thigh, coronet, vulva , udder, and axilla . In rare cases, mostly involving young lambs, lesions are found on the tongue, gums, roof of the mouth and the oesophagus. It has also been reported a number of times to cause lesions in the rumen. In one case it was shown that a severe form of orf virus caused an outbreak involving the gastrointestinal tract, lungs, heart, as well as the buccal cavity, cheeks, tongue and lips. Another severe case was reported pharyngitis, genital lesions and infection of the hooves which led to lameness and, in some cases, sloughing of the hoof. More typically, sheep will become free of orf within a week or so as the disease runs its course. Sheep custodians can assist by ensuring infected lambs receive sufficient milk and separating out the infected stock to slow down cross-transmission to healthy animals. It is advisable for those handling infected animals to wear disposable gloves to prevent cross infection and self-infection. A veterinarian must be contacted if there is a risk of misdiagnosis with other, more serious conditions.

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Virus-like_particle/html

Virus-like particle

Virus-like particles (VLPs) are molecules that closely resemble viruses , but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly (i.e., assembly inside E. coli bacteria via recombinant co-expression of multiple proteins) and in-vitro assembly (i.e., protein self-assembly in a reaction vessel using stoichiometric quantities of previously purified proteins) have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen ( HBsAg ) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus ), Retroviridae (e.g. HIV ), Flaviviridae (e.g. Hepatitis C virus ), Paramyxoviridae (e.g. Nipah ) and bacteriophages (e.g. Qβ, AP205). VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells. VLPs can also refer to structures produced by some LTR retrotransposons (under Ortervirales ) in nature. These are defective, immature virions , sometimes containing genetic material, that are generally non-infective due to the lack of a functional viral envelope . In addition, wasps produce polydnavirus vectors with pathogenic genes (but not core viral genes) or gene-less VLPs to help control their host. VLPs are a candidate delivery system for genes or other therapeutics. These drug delivery agents have been shown to effectively target cancer cells in vitro . It is hypothesized that VLPs may accumulate in tumor sites due to the enhanced permeability and retention effect , which could be useful for drug delivery or tumor imaging. VLPs are useful as vaccines . VLPs contain repetitive, high density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses . The particles' small radius of roughly 20-200 nm allows sufficient draining into lymph nodes . Since VLPs cannot replicate, they provide a safer alternative to attenuated viruses . VLPs were used to develop FDA-approved vaccines for Hepatitis B and human papillomavirus , which are commercially available. A selection of viruslike particle-based vaccines against human papilloma virus (HPV) such as Cervarix by GlaxoSmithKline along with Gardasil and Gardasil-9, are available, produced by Merck & Co . Gardasil consists of recombinant VLPs assembled from the L1 proteins of HPV types 6, 11, 16, and 18 expressed in yeast . It is adjuvanted with aluminum hydroxyphosphate sulfate. Gardasil-9 consists of L1 epitopes of 31, 33, 45, 52 and 58 in addition to the listed L1 epitopes found in Gardasil. Cervarix consists of recombinant VLPs assembled from the L1 proteins of HPV types 16 and 18, expressed in insect cells, and is adjuvanted with 3-O-Desacyl-4-monophosphoryl lipid (MPL) A and aluminum hydroxide. The first VLP vaccine that addresses malaria, Mosquirix, ( RTS,S ) has been approved by EU regulators. It was expressed in yeast. RTS,S is a portion of the Plasmodium falciparum circumsporozoite protein fused to the Hepatitis B surface antigen (RTS), combined with Hepatitis B surface antigen (S), and adjuvanted with AS01 (consisting of (MPL)A and saponin ). Vaccine production can begin as soon as the virus strain is sequenced and can take as little as 12 weeks, compared to 9 months for traditional vaccines. In early clinical trials, VLP vaccines for influenza appeared to provide complete protection against both the Influenza A virus subtype H5N1 and the 1918 flu pandemic . Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines. Several VLP vaccines for COVID-19 , including Novavax , are under development. VLPs have been used to develop a pre-clinical vaccine candidate against chikungunya virus. Compartmentalization is a common theme in biology. Nature is full of examples of hierarchically compartmentalized multicomponent structures that self-assembles from individual building blocks. Taking inspiration from nature, synthetic approaches using polymers, phase-separated microdroplets, lipids and proteins have been used to mimic hierarchical compartmentalization of natural systems and to form functional bio-inspired nanomaterials. For example, protein self-assembly was used to encapsulate multiple copies of ferritin protein cages as sub-compartments inside P22 virus-like particle as larger compartment essentially forming a Matryoshka-like nested cage-within-cage structure. The authors further demonstrated stoichiometric encapsulation of cellobiose-hydrolysing β-glycosidase enzyme CelB along with ferritin protein cages using in-vitro self-assembly strategy to form multi-compartment cell-inspired protein cage structure. Using similar strategy, glutathione biosynthesizing enzymes were encapsulated inside bacteriophage P22 virus-like particles. In a separate research, 3.5 nm small Cytochrome C with peroxidase-like activity was encapsulated inside a 9 nm small Dps protein cage to form organelle-inspired protein cage structure. The VLP lipoparticle was developed to aid the study of integral membrane proteins . Lipoparticles are stable, highly purified, homogeneous VLPs that are engineered to contain high concentrations of a conformationally intact membrane protein of interest. Integral Membrane proteins are involved in diverse biological functions and are targeted by nearly 50% of existing therapeutic drugs. However, because of their hydrophobic domains, membrane proteins are difficult to manipulate outside of living cells. Lipoparticles can incorporate a wide variety of structurally intact membrane proteins, including G protein-coupled receptors (GPCR)s, ion channels and viral Envelopes. Lipoparticles provide a platform for numerous applications including antibody screening, production of immunogens and ligand binding assays. VLPs are a candidate delivery system for genes or other therapeutics. These drug delivery agents have been shown to effectively target cancer cells in vitro . It is hypothesized that VLPs may accumulate in tumor sites due to the enhanced permeability and retention effect , which could be useful for drug delivery or tumor imaging. VLPs are useful as vaccines . VLPs contain repetitive, high density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses . The particles' small radius of roughly 20-200 nm allows sufficient draining into lymph nodes . Since VLPs cannot replicate, they provide a safer alternative to attenuated viruses . VLPs were used to develop FDA-approved vaccines for Hepatitis B and human papillomavirus , which are commercially available. A selection of viruslike particle-based vaccines against human papilloma virus (HPV) such as Cervarix by GlaxoSmithKline along with Gardasil and Gardasil-9, are available, produced by Merck & Co . Gardasil consists of recombinant VLPs assembled from the L1 proteins of HPV types 6, 11, 16, and 18 expressed in yeast . It is adjuvanted with aluminum hydroxyphosphate sulfate. Gardasil-9 consists of L1 epitopes of 31, 33, 45, 52 and 58 in addition to the listed L1 epitopes found in Gardasil. Cervarix consists of recombinant VLPs assembled from the L1 proteins of HPV types 16 and 18, expressed in insect cells, and is adjuvanted with 3-O-Desacyl-4-monophosphoryl lipid (MPL) A and aluminum hydroxide. The first VLP vaccine that addresses malaria, Mosquirix, ( RTS,S ) has been approved by EU regulators. It was expressed in yeast. RTS,S is a portion of the Plasmodium falciparum circumsporozoite protein fused to the Hepatitis B surface antigen (RTS), combined with Hepatitis B surface antigen (S), and adjuvanted with AS01 (consisting of (MPL)A and saponin ). Vaccine production can begin as soon as the virus strain is sequenced and can take as little as 12 weeks, compared to 9 months for traditional vaccines. In early clinical trials, VLP vaccines for influenza appeared to provide complete protection against both the Influenza A virus subtype H5N1 and the 1918 flu pandemic . Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines. Several VLP vaccines for COVID-19 , including Novavax , are under development. VLPs have been used to develop a pre-clinical vaccine candidate against chikungunya virus. Compartmentalization is a common theme in biology. Nature is full of examples of hierarchically compartmentalized multicomponent structures that self-assembles from individual building blocks. Taking inspiration from nature, synthetic approaches using polymers, phase-separated microdroplets, lipids and proteins have been used to mimic hierarchical compartmentalization of natural systems and to form functional bio-inspired nanomaterials. For example, protein self-assembly was used to encapsulate multiple copies of ferritin protein cages as sub-compartments inside P22 virus-like particle as larger compartment essentially forming a Matryoshka-like nested cage-within-cage structure. The authors further demonstrated stoichiometric encapsulation of cellobiose-hydrolysing β-glycosidase enzyme CelB along with ferritin protein cages using in-vitro self-assembly strategy to form multi-compartment cell-inspired protein cage structure. Using similar strategy, glutathione biosynthesizing enzymes were encapsulated inside bacteriophage P22 virus-like particles. In a separate research, 3.5 nm small Cytochrome C with peroxidase-like activity was encapsulated inside a 9 nm small Dps protein cage to form organelle-inspired protein cage structure. The VLP lipoparticle was developed to aid the study of integral membrane proteins . Lipoparticles are stable, highly purified, homogeneous VLPs that are engineered to contain high concentrations of a conformationally intact membrane protein of interest. Integral Membrane proteins are involved in diverse biological functions and are targeted by nearly 50% of existing therapeutic drugs. However, because of their hydrophobic domains, membrane proteins are difficult to manipulate outside of living cells. Lipoparticles can incorporate a wide variety of structurally intact membrane proteins, including G protein-coupled receptors (GPCR)s, ion channels and viral Envelopes. Lipoparticles provide a platform for numerous applications including antibody screening, production of immunogens and ligand binding assays. The understanding of self-assembly of VLPs was once based on viral assembly. This is rational as long as the VLP assembly takes place inside the host cell ( in vivo ), though the self-assembly event was found in vitro from the very beginning of the study about viral assembly. Study also reveals that in vitro assembly of VLPs competes with aggregation and certain mechanisms exist inside the cell to prevent the formation of aggregates while assembly is ongoing. Attaching proteins, nucleic acids, or small molecules to the VLP surface, such as for targeting a specific cell type or for raising an immune response is useful. In some cases a protein of interest can be genetically fused to the viral coat protein. However, this approach sometimes leads to impaired VLP assembly and has limited utility if the targeting agent is not protein-based. An alternative is to assemble the VLP and then use chemical crosslinkers, reactive unnatural amino acids or SpyTag/SpyCatcher reaction in order to covalently attach the molecule of interest. This method is effective at directing the immune response against the attached molecule, thereby inducing high levels of neutralizing antibody and even being able to break tolerance to self-proteins displayed on VLPs.

Wiki

Chikungunya

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

Lyme disease

Lyme disease , also known as Lyme borreliosis , is a vector-borne disease caused by Borrelia bacteria, which are spread by ticks in the genus Ixodes . The most common sign of infection is an expanding red rash , known as erythema migrans (EM), which appears at the site of the tick bite about a week afterwards. The rash is typically neither itchy nor painful. Approximately 70–80% of infected people develop a rash. Early diagnosis can be difficult. Other early symptoms may include fever, headaches and tiredness . If untreated, symptoms may include loss of the ability to move one or both sides of the face , joint pains , severe headaches with neck stiffness or heart palpitations . Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, shooting pains or tingling in the arms and legs may develop. Despite appropriate treatment, about 10 to 20% of those affected develop joint pains, memory problems, and tiredness for at least six months. Lyme disease is transmitted to humans by the bites of infected ticks of the genus Ixodes . In the United States, ticks of concern are usually of the Ixodes scapularis type. According to the Centers for Disease Control and Prevention , "In most cases, a tick must be attached for 36 to 48 hours or more before the Lyme disease bacterium can be transmitted. If you remove a tick quickly (within 24 hours), you can greatly reduce your chances of getting Lyme disease." In Europe, Ixodes ricinus ticks may spread the bacteria more quickly. In North America, the bacterial species Borrelia burgdorferi and B. mayonii cause Lyme disease. In Europe and Asia, Borrelia afzelii , Borrelia garinii , B. spielmanii and four other species also cause the disease. The disease does not appear to be transmissible between people, by other animals nor through food. Diagnosis is based on a combination of symptoms, history of tick exposure and possibly testing for specific antibodies in the blood. Blood tests are often falsely negative in the early stages of the disease. Testing of individual ticks is not typically useful. Prevention includes efforts to prevent tick bites by wearing clothing to cover the arms and legs and using DEET or picaridin -based insect repellents . Using pesticides to reduce tick numbers may also be effective. Ticks can be removed using tweezers . If the removed tick is full of blood a single dose of doxycycline may be used to prevent the development of infection but is not generally recommended since the development of infection is rare. If an infection develops, a number of antibiotics are effective, including doxycycline, amoxicillin and cefuroxime . Standard treatment usually lasts for two or three weeks. Some people develop a fever and muscle and joint pains from treatment, which may last for one or two days. In those who develop persistent symptoms, long-term antibiotic therapy has not been found to be useful. Lyme disease is the most common disease spread by ticks in the Northern Hemisphere. Infections are most common in the spring and early summer. Lyme disease was diagnosed as a separate condition for the first time in 1975 in Lyme, Connecticut . It was originally mistaken for juvenile rheumatoid arthritis . The bacterium involved was first described in 1981 by Willy Burgdorfer . Chronic symptoms following treatment are known as "post-treatment Lyme disease syndrome" (PTLDS). PTLDS is different from chronic Lyme disease , a term no longer supported by scientists and used in different ways by different groups. Some healthcare providers claim that PTLDS is caused by persistent infection, but this is not believed to be true because no evidence of persistent infection can be found after standard treatment. As of 2023 [ update ] clinical trials of proposed human vaccines for Lyme disease were being carried out, but no vaccine was available. A vaccine, LYMERix, was produced, but discontinued in 2002 due to insufficient demand. There are several vaccines for the prevention of Lyme disease in dogs.Lyme disease can produce a broad range of symptoms. The incubation period is usually one to two weeks, but can be much shorter (days) or much longer (months to years). Lyme symptoms most often occur from the month of May to September in the Northern Hemisphere because the nymphal stage of the tick is responsible for most cases. 80% of Lyme infections begin with a rash of some sort at the site of a tick bite, often near skin folds such as the armpit , groin , back of the knee , or the trunk under clothing straps, or in children's hair, ears, or neck. Most people who get infected do not remember seeing a tick or a bite. The rash appears typically one or two weeks (range 3–32 days) after the bite and expands 2–3 cm per day up to a diameter of 5–70 cm (median is 16 cm). The rash is usually circular or oval, red or bluish, and may have an elevated or darker center. This rash is termed an Erythema Migrans (EM) which translates as "Redness Migrating." In about 79% of cases in Europe, this rash gradually clears from the center toward the edges possibly forming a "bull's eye" or "target-like" pattern, but this clearing only happens in 19% of cases in endemic areas of the United States. The rash may feel warm, usually is not itchy, is rarely tender or painful, and takes up to four weeks to resolve if untreated. The Lyme rash is often accompanied by symptoms of a flu-like illness, including fatigue, headache, body aches, fever, and chills [though usually neither nausea nor upper-respiratory problems]. These symptoms may also appear without a rash or linger after the rash has disappeared. Lyme can progress to later stages without a rash or these symptoms. People with high fever for more than two days or whose other symptoms of viral-like illness do not improve despite antibiotic treatment for Lyme disease, or who have abnormally low levels of white or red cells or platelets in the blood, should be investigated for possible coinfection with other tick-borne diseases such as ehrlichiosis and babesiosis . Of course, not everyone with Lyme disease has all the symptoms, and many of these symptoms can occur with other diseases as well. Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States. Asymptomatic infection may be much more common among those infected in Europe. Within days to weeks after the onset of local infection, the Borrelia bacteria may spread through the lymphatic system or bloodstream. In 10–20% of untreated cases, EM rashes develop at sites across the body that bear no relation to the original tick bite. Transient muscle pains and joint pains are also common. In about 10–15% of untreated people, Lyme causes neurological problems known as neuroborreliosis . Early neuroborreliosis typically appears 4–6 weeks (range 1–12 weeks) after the tick bite and involves some combination of lymphocytic meningitis, cranial neuritis, radiculopathy, and/or mononeuritis multiplex. Lymphocytic meningitis causes characteristic changes in the cerebrospinal fluid (CSF) and may be accompanied for several weeks by variable headache and, less commonly, usually mild meningitis signs such as inability to flex the neck fully and intolerance to bright lights but typically no or only very low fever. After several months neuroborreliosis can also present otolaryngological symptoms . Up to 76.5% of them present as tinnitus , the most common symptom. Vertigo and dizziness (53.7%) and hearing loss (16.7%) were the next most common symptoms. In children partial loss of vision may also occur. Cranial neuritis is an inflammation of cranial nerves . When due to Lyme, it most typically causes facial palsy , impairing blinking, smiling, and chewing on one or both sides of the face. It may also cause intermittent double vision . Lyme radiculopathy is an inflammation of spinal nerve roots that often causes pain and less often weakness , numbness , or altered sensation in the areas of the body served by nerves connected to the affected roots , e.g. limb(s) or part(s) of trunk. The pain is often described as unlike any other previously felt, excruciating, migrating, worse at night, rarely symmetrical, and often accompanied by extreme sleep disturbance. Mononeuritis multiplex is an inflammation causing similar symptoms in one or more unrelated peripheral nerves. Rarely, early neuroborreliosis may involve inflammation of the brain or spinal cord , with symptoms such as confusion, abnormal gait, ocular movements, or speech , impaired movement , impaired motor planning , or shaking . In North America, facial palsy is the typical early neuroborreliosis presentation, occurring in 5–10% of untreated people, in about 75% of cases accompanied by lymphocytic meningitis. Lyme radiculopathy is reported half as frequently, but many cases may be unrecognized. In European adults, the most common presentation is a combination of lymphocytic meningitis and radiculopathy known as Bannwarth syndrome , accompanied in 36-89% of cases by facial palsy. In this syndrome, radicular pain tends to start in the same body region as the initial erythema migrans rash, if there was one, and precedes possible facial palsy and other impaired movement . In extreme cases, permanent impairment of motor or sensory function of the lower limbs may occur. In European children, the most common manifestations are facial palsy (in 55%), other cranial neuritis, and lymphocytic meningitis (in 27%). In about 4–10% of untreated cases in the U.S. and 0.3–4% of untreated cases in Europe, typically between June and December, about one month (range 4 days – 7 months) after the tick bite, the infection may cause heart complications known as Lyme carditis . Symptoms may include heart palpitations (in 69% of people), dizziness , fainting , shortness of breath , and chest pain . Other symptoms of Lyme disease may also be present, such as EM rash, joint aches , facial palsy , headaches , or radicular pain . In some people, however, carditis may be the first manifestation of Lyme disease. Lyme carditis in 19–87% of people adversely impacts the heart's electrical conduction system, causing atrioventricular block that often manifests as heart rhythms that alternate within minutes between abnormally slow and abnormally fast. In 10–15% of people, Lyme causes myocardial complications such as cardiomegaly , left ventricular dysfunction, or congestive heart failure. Another skin condition, found in Europe but not in North America, is borrelial lymphocytoma , a purplish lump that develops on the ear lobe, nipple, or scrotum . Lyme arthritis occurs in up to 60% of untreated people, typically starting about six months after infection. It usually affects only one or a few joints, often a knee or possibly the hip , other large joints, or the temporomandibular joint . Usually, large joint effusion and swelling occur, but only mild or moderate pain. Without treatment, swelling and pain typically resolve over time, but periodically return. Baker's cysts may form and rupture. In early US studies of Lyme disease, a rare peripheral neuropathy was described that included numbness, tingling, or burning starting at the feet or hands and over time possibly moving up the limbs. In a later analysis that discovered poor documentation of this manifestation, experts wondered if it exists at all in the US or is merely very rare. A neurologic syndrome called Lyme encephalopathy is associated with subtle memory and cognitive difficulties, insomnia , a general sense of feeling unwell , and changes in personality. Lyme encephalopathy is controversial in the US and has not been reported in Europe. Problems such as depression and fibromyalgia are as common in people with Lyme disease as in the general population. There is no compelling evidence that Lyme disease causes psychiatric disorders, behavioral disorders (e.g. ADHD ), or developmental disorders (e.g. autism ). Acrodermatitis chronica atrophicans is a chronic skin disorder observed primarily in Europe among the elderly. It begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless. It is also associated with peripheral neuropathy. 80% of Lyme infections begin with a rash of some sort at the site of a tick bite, often near skin folds such as the armpit , groin , back of the knee , or the trunk under clothing straps, or in children's hair, ears, or neck. Most people who get infected do not remember seeing a tick or a bite. The rash appears typically one or two weeks (range 3–32 days) after the bite and expands 2–3 cm per day up to a diameter of 5–70 cm (median is 16 cm). The rash is usually circular or oval, red or bluish, and may have an elevated or darker center. This rash is termed an Erythema Migrans (EM) which translates as "Redness Migrating." In about 79% of cases in Europe, this rash gradually clears from the center toward the edges possibly forming a "bull's eye" or "target-like" pattern, but this clearing only happens in 19% of cases in endemic areas of the United States. The rash may feel warm, usually is not itchy, is rarely tender or painful, and takes up to four weeks to resolve if untreated. The Lyme rash is often accompanied by symptoms of a flu-like illness, including fatigue, headache, body aches, fever, and chills [though usually neither nausea nor upper-respiratory problems]. These symptoms may also appear without a rash or linger after the rash has disappeared. Lyme can progress to later stages without a rash or these symptoms. People with high fever for more than two days or whose other symptoms of viral-like illness do not improve despite antibiotic treatment for Lyme disease, or who have abnormally low levels of white or red cells or platelets in the blood, should be investigated for possible coinfection with other tick-borne diseases such as ehrlichiosis and babesiosis . Of course, not everyone with Lyme disease has all the symptoms, and many of these symptoms can occur with other diseases as well. Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States. Asymptomatic infection may be much more common among those infected in Europe. Within days to weeks after the onset of local infection, the Borrelia bacteria may spread through the lymphatic system or bloodstream. In 10–20% of untreated cases, EM rashes develop at sites across the body that bear no relation to the original tick bite. Transient muscle pains and joint pains are also common. In about 10–15% of untreated people, Lyme causes neurological problems known as neuroborreliosis . Early neuroborreliosis typically appears 4–6 weeks (range 1–12 weeks) after the tick bite and involves some combination of lymphocytic meningitis, cranial neuritis, radiculopathy, and/or mononeuritis multiplex. Lymphocytic meningitis causes characteristic changes in the cerebrospinal fluid (CSF) and may be accompanied for several weeks by variable headache and, less commonly, usually mild meningitis signs such as inability to flex the neck fully and intolerance to bright lights but typically no or only very low fever. After several months neuroborreliosis can also present otolaryngological symptoms . Up to 76.5% of them present as tinnitus , the most common symptom. Vertigo and dizziness (53.7%) and hearing loss (16.7%) were the next most common symptoms. In children partial loss of vision may also occur. Cranial neuritis is an inflammation of cranial nerves . When due to Lyme, it most typically causes facial palsy , impairing blinking, smiling, and chewing on one or both sides of the face. It may also cause intermittent double vision . Lyme radiculopathy is an inflammation of spinal nerve roots that often causes pain and less often weakness , numbness , or altered sensation in the areas of the body served by nerves connected to the affected roots , e.g. limb(s) or part(s) of trunk. The pain is often described as unlike any other previously felt, excruciating, migrating, worse at night, rarely symmetrical, and often accompanied by extreme sleep disturbance. Mononeuritis multiplex is an inflammation causing similar symptoms in one or more unrelated peripheral nerves. Rarely, early neuroborreliosis may involve inflammation of the brain or spinal cord , with symptoms such as confusion, abnormal gait, ocular movements, or speech , impaired movement , impaired motor planning , or shaking . In North America, facial palsy is the typical early neuroborreliosis presentation, occurring in 5–10% of untreated people, in about 75% of cases accompanied by lymphocytic meningitis. Lyme radiculopathy is reported half as frequently, but many cases may be unrecognized. In European adults, the most common presentation is a combination of lymphocytic meningitis and radiculopathy known as Bannwarth syndrome , accompanied in 36-89% of cases by facial palsy. In this syndrome, radicular pain tends to start in the same body region as the initial erythema migrans rash, if there was one, and precedes possible facial palsy and other impaired movement . In extreme cases, permanent impairment of motor or sensory function of the lower limbs may occur. In European children, the most common manifestations are facial palsy (in 55%), other cranial neuritis, and lymphocytic meningitis (in 27%). In about 4–10% of untreated cases in the U.S. and 0.3–4% of untreated cases in Europe, typically between June and December, about one month (range 4 days – 7 months) after the tick bite, the infection may cause heart complications known as Lyme carditis . Symptoms may include heart palpitations (in 69% of people), dizziness , fainting , shortness of breath , and chest pain . Other symptoms of Lyme disease may also be present, such as EM rash, joint aches , facial palsy , headaches , or radicular pain . In some people, however, carditis may be the first manifestation of Lyme disease. Lyme carditis in 19–87% of people adversely impacts the heart's electrical conduction system, causing atrioventricular block that often manifests as heart rhythms that alternate within minutes between abnormally slow and abnormally fast. In 10–15% of people, Lyme causes myocardial complications such as cardiomegaly , left ventricular dysfunction, or congestive heart failure. Another skin condition, found in Europe but not in North America, is borrelial lymphocytoma , a purplish lump that develops on the ear lobe, nipple, or scrotum . Lyme arthritis occurs in up to 60% of untreated people, typically starting about six months after infection. It usually affects only one or a few joints, often a knee or possibly the hip , other large joints, or the temporomandibular joint . Usually, large joint effusion and swelling occur, but only mild or moderate pain. Without treatment, swelling and pain typically resolve over time, but periodically return. Baker's cysts may form and rupture. In early US studies of Lyme disease, a rare peripheral neuropathy was described that included numbness, tingling, or burning starting at the feet or hands and over time possibly moving up the limbs. In a later analysis that discovered poor documentation of this manifestation, experts wondered if it exists at all in the US or is merely very rare. A neurologic syndrome called Lyme encephalopathy is associated with subtle memory and cognitive difficulties, insomnia , a general sense of feeling unwell , and changes in personality. Lyme encephalopathy is controversial in the US and has not been reported in Europe. Problems such as depression and fibromyalgia are as common in people with Lyme disease as in the general population. There is no compelling evidence that Lyme disease causes psychiatric disorders, behavioral disorders (e.g. ADHD ), or developmental disorders (e.g. autism ). Acrodermatitis chronica atrophicans is a chronic skin disorder observed primarily in Europe among the elderly. It begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless. It is also associated with peripheral neuropathy. Lyme disease is caused by spirochetes , spiral bacteria from the genus Borrelia . Spirochetes are surrounded by peptidoglycan and flagella , along with an outer membrane similar to Gram-negative bacteria. Because of their double-membrane envelope, Borrelia bacteria are often mistakenly described as Gram negative despite the considerable differences in their envelope components from Gram-negative bacteria. The Lyme-related Borrelia species are collectively known as Borrelia burgdorferi sensu lato , and show a great deal of genetic diversity . B. burgdorferi sensu lato is a species complex made up of 20 accepted and three proposed genospecies. Eight species are known to cause Lyme disease: B. mayonii (found in North America), B. burgdorferi sensu stricto (found in North America and Europe), B. afzelii , B. garinii, B. spielmanii, and B. lusitaniae (all found in Eurasia ). Some studies have also proposed that B. valaisiana may sometimes infect humans, but this species does not seem to be an important cause of disease. Three stages occur in the life cycle of a tick - larva, nymph, and adult. During the nymph stage, ticks most frequently transmit Lyme disease and are usually most active in late spring and early summer in regions where the climate is mild. During the adult stage, Lyme disease transmission is less common because adult ticks are less likely to bite humans and tend to be larger in size, so can be easily seen and removed. Lyme disease is classified as a zoonosis , as it is transmitted to humans from a natural reservoir among small mammals and birds by ticks that feed on both sets of hosts . Hard-bodied ticks of the genus Ixodes are the vectors of Lyme disease (also the vector for Babesia ). Most infections are caused by ticks in the nymphal stage , because they are very small, thus may feed for long periods of time undetected. Nymphal ticks are generally the size of a poppy seed and sometimes with a dark head and a translucent body. Or, the nymphal ticks can be darker. The younger larval ticks are very rarely infected. Although deer are the preferred hosts of adult deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire Borrelia from deer, instead they obtain them from infected small mammals such as the white-footed mouse , and occasionally birds. Areas where Lyme is common are expanding. Within the tick midgut, the Borrelia ' s outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. When the tick feeds, the Borrelia downregulates OspA and upregulates OspC, another surface protein. After the bacteria migrate from the midgut to the salivary glands, OspC binds to Salp15, a tick salivary protein that appears to have immunosuppressive effects that enhance infection. Successful infection of the mammalian host depends on bacterial expression of OspC. Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. However, transmission is quite rare, with only about 1.2 to 1.4 percent of recognized tick bites resulting in Lyme disease. While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice , Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, and Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto . The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association. Budding research has suggested that B. burgdorferi sensu lato may also be able to form enzootic cycle among lizard populations; this was previously assumed not to be possible in major areas containing populations of lizards, such as California. Except for one study in Europe, much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated that lizards are able to infect ticks feeding upon them. As some experiments suggest lizards are refractory to infection with Borrelia , it appears likely their involvement in the enzootic cycle is more complex and species-specific. In Europe, the main vector is Ixodes ricinus , which is also called the sheep tick or castor bean tick. In China, Ixodes persulcatus (the taiga tick) is probably the most important vector. In North America, the black-legged tick or deer tick ( Ixodes scapularis ) is the main vector on the East Coast. The lone star tick ( Amblyomma americanum ), which is found throughout the Southeastern United States as far west as Texas , is unlikely to transmit the Lyme disease spirochetes , though it may be implicated in a related syndrome called southern tick-associated rash illness , which resembles a mild form of Lyme disease. On the West Coast of the United States , the main vector is the western black-legged tick ( Ixodes pacificus ). The tendency of this tick species to feed predominantly on host species such as the Western Fence Lizard that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West. Transmission can occur across the placenta during pregnancy and as with a number of other spirochetal diseases, adverse pregnancy outcomes are possible with untreated infection; prompt treatment with antibiotics reduces or eliminates this risk. There is no scientific evidence to support Lyme disease transmission via blood transfusion, sexual contact, or breast milk. Ticks that transmit B. burgdorferi to humans can also carry and transmit several other microbes, such as Babesia microti and Anaplasma phagocytophilum , which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively. Among people with early Lyme disease, depending on their location, 2–12% will also have HGA and 2–10% will have babesiosis. Ticks in certain regions also transmit viruses that cause tick-borne encephalitis and Powassan virus disease . Co-infections of Lyme disease may not require additional treatment, since they may resolve on their own or—as in the case of HGA—can be treated with the doxycycline prescribed for Lyme. Persistent fever or compatible anomalous laboratory findings may be indicative of a co-infection. Three stages occur in the life cycle of a tick - larva, nymph, and adult. During the nymph stage, ticks most frequently transmit Lyme disease and are usually most active in late spring and early summer in regions where the climate is mild. During the adult stage, Lyme disease transmission is less common because adult ticks are less likely to bite humans and tend to be larger in size, so can be easily seen and removed. Lyme disease is classified as a zoonosis , as it is transmitted to humans from a natural reservoir among small mammals and birds by ticks that feed on both sets of hosts . Hard-bodied ticks of the genus Ixodes are the vectors of Lyme disease (also the vector for Babesia ). Most infections are caused by ticks in the nymphal stage , because they are very small, thus may feed for long periods of time undetected. Nymphal ticks are generally the size of a poppy seed and sometimes with a dark head and a translucent body. Or, the nymphal ticks can be darker. The younger larval ticks are very rarely infected. Although deer are the preferred hosts of adult deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire Borrelia from deer, instead they obtain them from infected small mammals such as the white-footed mouse , and occasionally birds. Areas where Lyme is common are expanding. Within the tick midgut, the Borrelia ' s outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. When the tick feeds, the Borrelia downregulates OspA and upregulates OspC, another surface protein. After the bacteria migrate from the midgut to the salivary glands, OspC binds to Salp15, a tick salivary protein that appears to have immunosuppressive effects that enhance infection. Successful infection of the mammalian host depends on bacterial expression of OspC. Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. However, transmission is quite rare, with only about 1.2 to 1.4 percent of recognized tick bites resulting in Lyme disease. While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice , Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, and Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto . The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association. Budding research has suggested that B. burgdorferi sensu lato may also be able to form enzootic cycle among lizard populations; this was previously assumed not to be possible in major areas containing populations of lizards, such as California. Except for one study in Europe, much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated that lizards are able to infect ticks feeding upon them. As some experiments suggest lizards are refractory to infection with Borrelia , it appears likely their involvement in the enzootic cycle is more complex and species-specific. In Europe, the main vector is Ixodes ricinus , which is also called the sheep tick or castor bean tick. In China, Ixodes persulcatus (the taiga tick) is probably the most important vector. In North America, the black-legged tick or deer tick ( Ixodes scapularis ) is the main vector on the East Coast. The lone star tick ( Amblyomma americanum ), which is found throughout the Southeastern United States as far west as Texas , is unlikely to transmit the Lyme disease spirochetes , though it may be implicated in a related syndrome called southern tick-associated rash illness , which resembles a mild form of Lyme disease. On the West Coast of the United States , the main vector is the western black-legged tick ( Ixodes pacificus ). The tendency of this tick species to feed predominantly on host species such as the Western Fence Lizard that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West. Transmission can occur across the placenta during pregnancy and as with a number of other spirochetal diseases, adverse pregnancy outcomes are possible with untreated infection; prompt treatment with antibiotics reduces or eliminates this risk. There is no scientific evidence to support Lyme disease transmission via blood transfusion, sexual contact, or breast milk. Ticks that transmit B. burgdorferi to humans can also carry and transmit several other microbes, such as Babesia microti and Anaplasma phagocytophilum , which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively. Among people with early Lyme disease, depending on their location, 2–12% will also have HGA and 2–10% will have babesiosis. Ticks in certain regions also transmit viruses that cause tick-borne encephalitis and Powassan virus disease . Co-infections of Lyme disease may not require additional treatment, since they may resolve on their own or—as in the case of HGA—can be treated with the doxycycline prescribed for Lyme. Persistent fever or compatible anomalous laboratory findings may be indicative of a co-infection. B. burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system. B. Burgdorferi does not produce toxins. Therefore, many of the signs and symptoms of Lyme disease are a consequence of the immune response to spirochete in those tissues. B. burgdorferi is injected into the skin by the bite of an infected Ixodes tick. Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis . The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion. Neutrophils , however, which are necessary to eliminate the spirochetes from the skin, fail to appear in necessary numbers in the developing EM lesion because tick saliva inhibits neutrophil function. This allows the bacteria to survive and eventually spread throughout the body. Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of the disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete. If untreated, the bacteria may persist in the body for months or even years, despite the production of B. burgdorferi antibodies by the immune system. The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, antigenic variation of the VlsE surface protein, inactivating key immune components such as complement , and hiding in the extracellular matrix , which may interfere with the function of immune factors. Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response , a form of pathogen-induced autoimmune disease. The production of this reaction might be due to a form of molecular mimicry , where Borrelia avoids being killed by the immune system by resembling normal parts of the body's tissues. Chronic symptoms from an autoimmune reaction could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to rheumatic fever , but its wider application is controversial. Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response , a form of pathogen-induced autoimmune disease. The production of this reaction might be due to a form of molecular mimicry , where Borrelia avoids being killed by the immune system by resembling normal parts of the body's tissues. Chronic symptoms from an autoimmune reaction could explain why some symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to rheumatic fever , but its wider application is controversial. Lyme disease is diagnosed based on symptoms, objective physical findings (such as erythema migrans (EM) rash, facial palsy , or arthritis ), history of possible exposure to infected ticks , and possibly laboratory tests . People with symptoms of early Lyme disease should have a total body skin examination for EM rashes and asked whether EM-type rashes had manifested within the last 1–2 months. Presence of an EM rash and recent tick exposure (i.e., being outdoors in a likely tick habitat where Lyme is common , within 30 days of the appearance of the rash) are sufficient for Lyme diagnosis; no laboratory confirmation is needed or recommended. Most people who get infected do not remember a tick or a bite, and the EM rash need not look like a bull's eye (most EM rashes in the U.S. do not) or be accompanied by any other symptoms. In the U.S., Lyme is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota , but it is expanding into other areas. Several bordering areas of Canada also have high Lyme risk. In the absence of an EM rash or history of tick exposure, Lyme diagnosis depends on laboratory confirmation. The bacteria that cause Lyme disease are difficult to observe directly in body tissues and also difficult and too time-consuming to grow in the laboratory. The most widely used tests look instead for presence of antibodies against those bacteria in the blood. A positive antibody test result does not by itself prove active infection but can confirm an infection that is suspected because of symptoms, objective findings, and history of tick exposure in a person. Because as many as 5–20% of the normal population have antibodies against Lyme, people without history and symptoms suggestive of Lyme disease should not be tested for Lyme antibodies: a positive result would likely be false, possibly causing unnecessary treatment. In some cases, when history, signs, and symptoms are strongly suggestive of early disseminated Lyme disease, empiric treatment may be started and reevaluated as laboratory test results become available. Tests for antibodies in the blood by ELISA and Western blot is the most widely used method for Lyme diagnosis. A two-tiered protocol is recommended by the Centers for Disease Control and Prevention (CDC): the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run. The immune system takes some time to produce antibodies in quantity. After Lyme infection onset, antibodies of types IgM and IgG usually can first be detected respectively at 2–4 weeks and 4–6 weeks, and peak at 6–8 weeks. When an EM rash first appears, detectable antibodies may not be present. Therefore, it is recommended that testing not be performed and diagnosis be based on the presence of the EM rash. Up to 30 days after suspected Lyme infection onset, infection can be confirmed by detection of IgM or IgG antibodies; after that, it is recommended that only IgG antibodies be considered. A positive IgM and negative IgG test result after the first month of infection is generally indicative of a false-positive result. The number of IgM antibodies usually collapses 4–6 months after infection, while IgG antibodies can remain detectable for years. Other tests may be used in neuroborreliosis cases. In Europe, neuroborreliosis is usually caused by Borrelia garinii and almost always involves lymphocytic pleocytosis , i.e. the densities of lymphocytes (infection-fighting cells) and protein in the cerebrospinal fluid (CSF) typically rise to characteristically abnormal levels, while glucose level remains normal. Additionally, the immune system produces antibodies against Lyme inside the intrathecal space, which contains the CSF. Demonstration by lumbar puncture and CSF analysis of pleocytosis and intrathecal antibody production are required for definite diagnosis of neuroborreliosis in Europe (except in cases of peripheral neuropathy associated with acrodermatitis chronica atrophicans , which usually is caused by Borrelia afzelii and confirmed by blood antibody tests). In North America, neuroborreliosis is caused by Borrelia burgdorferi and may not be accompanied by the same CSF signs; they confirm a diagnosis of central nervous system (CNS) neuroborreliosis if positive, but do not exclude it if negative. American guidelines consider CSF analysis optional when symptoms appear to be confined to the peripheral nervous system (PNS), e.g. facial palsy without overt meningitis symptoms. Unlike blood and intrathecal antibody tests, CSF pleocytosis tests revert to normal after infection ends and therefore can be used as objective markers of treatment success and inform decisions on whether to retreat. In infection involving the PNS, electromyography and nerve conduction studies can be used to monitor objectively the response to treatment. In Lyme carditis, electrocardiograms are used to evidence heart conduction abnormalities, while echocardiography may show myocardial dysfunction. Biopsy and confirmation of Borrelia cells in myocardial tissue may be used in specific cases but are usually not done because of risk of the procedure. Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material ( DNA ) of the Lyme disease spirochete. Culture or PCR are the current means for detecting the presence of the organism, as serologic studies only test for antibodies of Borrelia . PCR has the advantage of being much faster than culture. However, PCR tests are susceptible to false positive results, e.g. by detection of debris of dead Borrelia cells or specimen contamination. Even when properly performed, PCR often shows false-negative results because few Borrelia cells can be found in blood and cerebrospinal fluid (CSF) during infection. Hence, PCR tests are recommended only in special cases, e.g. diagnosis of Lyme arthritis, because it is a highly sensitive way of detecting ospA DNA in synovial fluid. Although sensitivity of PCR in CSF is low, its use may be considered when intrathecal antibody production test results are suspected of being falsely negative, e.g. in very early (< 6 weeks) neuroborreliosis or in immunosuppressed people. Several other forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. OspA antigens , shed by live Borrelia bacteria into urine, are a promising technique being studied. The use of nanotrap particles for their detection is being looked at and the OspA has been linked to active symptoms of Lyme. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. The CDC does not recommend urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of B. burgdorferi , and lymphocyte transformation tests. Neuroimaging is controversial in whether it provides specific patterns unique to neuroborreliosis , but may aid in differential diagnosis and in understanding the pathophysiology of the disease. Though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a person. Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) are two of the tests that can identify abnormalities in the brain of a person affected with this disease. Neuroimaging findings in an MRI include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. The findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. Images produced using SPECT show numerous areas where an insufficient amount of blood is being delivered to the cortex and subcortical white matter. However, SPECT images are known to be nonspecific because they show a heterogeneous pattern in the imaging. The abnormalities seen in the SPECT images are very similar to those seen in people with cerebral vasculitis and Creutzfeldt–Jakob disease , which makes them questionable. Community clinics have been reported to misdiagnose 23–28% of Erythema migrans (EM) rashes and 83% of other objective manifestations of early Lyme disease. EM rashes are often misdiagnosed as spider bites , cellulitis , or shingles . Many misdiagnoses are credited to the widespread misconception that EM rashes should look like a bull's eye. Actually, the key distinguishing features of the EM rash are the speed and extent to which it expands, respectively up to 2–3 cm/day and a diameter of at least 5 cm, and in 50% of cases more than 16 cm. The rash expands away from its center, which may or may not look different or be separated by ring-like clearing from the rest of the rash. Compared to EM rashes, spider bites are more common in the limbs, tend to be more painful and itchy or become swollen, and some may cause necrosis (sinking dark blue patch of dead skin). Cellulitis most commonly develops around a wound or ulcer, is rarely circular, and is more likely to become swollen and tender. EM rashes often appear at sites that are unusual for cellulitis, such as the armpit, groin, abdomen, or back of knee. Like Lyme, shingles often begins with headache, fever, and fatigue, which are followed by pain or numbness. However, unlike Lyme, in shingles these symptoms are usually followed by appearance of rashes composed of multiple small blisters along with a nerve's dermatome , and shingles can also be confirmed by quick laboratory tests. Facial palsy caused by Lyme disease (LDFP) is often misdiagnosed as Bell's palsy . Although Bell's palsy is the most common type of one-sided facial palsy (about 70% of cases), LDFP can account for about 25% of cases of facial palsy in areas where Lyme disease is common. Compared to LDFP, Bell's palsy much less frequently affects both sides of the face. Even though LDFP and Bell's palsy have similar symptoms and evolve similarly if untreated, corticosteroid treatment is beneficial for Bell's Palsy, while being detrimental for LDFP. Recent history of exposure to a likely tick habitat during warmer months, EM rash, viral-like symptoms such as headache and fever, and/or palsy in both sides of the face should be evaluated for the likelihood of LDFP; if it is more than minimal, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease. Unlike viral meningitis , Lyme lymphocytic meningitis tends to not cause fever, last longer, and recur. Lymphocytic meningitis is also characterized by possibly co-occurring with EM rash , facial palsy , or partial vision obstruction and having much lower percentage of polymorphonuclear leukocytes in CSF . Lyme radiculopathy affecting the limbs is often misdiagnosed as a radiculopathy caused by nerve root compression, such as sciatica . Although most cases of radiculopathy are compressive and resolve with conservative treatment (e.g., rest) within 4–6 weeks, guidelines for managing radiculopathy recommend first evaluating risks of other possible causes that, although less frequent, require immediate diagnosis and treatment, including infections such as Lyme and shingles. A history of outdoor activities in likely tick habitats in the last 3 months possibly followed by a rash or viral-like symptoms, and current headache, other symptoms of lymphocytic meningitis, or facial palsy would lead to suspicion of Lyme disease and recommendation of serological and lumbar puncture tests for confirmation. Lyme radiculopathy affecting the trunk can be misdiagnosed as myriad other conditions, such as diverticulitis and acute coronary syndrome . Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator". As all people with later-stage infection will have a positive antibody test, simple blood tests can exclude Lyme disease as a possible cause of a person's symptoms. Tests for antibodies in the blood by ELISA and Western blot is the most widely used method for Lyme diagnosis. A two-tiered protocol is recommended by the Centers for Disease Control and Prevention (CDC): the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run. The immune system takes some time to produce antibodies in quantity. After Lyme infection onset, antibodies of types IgM and IgG usually can first be detected respectively at 2–4 weeks and 4–6 weeks, and peak at 6–8 weeks. When an EM rash first appears, detectable antibodies may not be present. Therefore, it is recommended that testing not be performed and diagnosis be based on the presence of the EM rash. Up to 30 days after suspected Lyme infection onset, infection can be confirmed by detection of IgM or IgG antibodies; after that, it is recommended that only IgG antibodies be considered. A positive IgM and negative IgG test result after the first month of infection is generally indicative of a false-positive result. The number of IgM antibodies usually collapses 4–6 months after infection, while IgG antibodies can remain detectable for years. Other tests may be used in neuroborreliosis cases. In Europe, neuroborreliosis is usually caused by Borrelia garinii and almost always involves lymphocytic pleocytosis , i.e. the densities of lymphocytes (infection-fighting cells) and protein in the cerebrospinal fluid (CSF) typically rise to characteristically abnormal levels, while glucose level remains normal. Additionally, the immune system produces antibodies against Lyme inside the intrathecal space, which contains the CSF. Demonstration by lumbar puncture and CSF analysis of pleocytosis and intrathecal antibody production are required for definite diagnosis of neuroborreliosis in Europe (except in cases of peripheral neuropathy associated with acrodermatitis chronica atrophicans , which usually is caused by Borrelia afzelii and confirmed by blood antibody tests). In North America, neuroborreliosis is caused by Borrelia burgdorferi and may not be accompanied by the same CSF signs; they confirm a diagnosis of central nervous system (CNS) neuroborreliosis if positive, but do not exclude it if negative. American guidelines consider CSF analysis optional when symptoms appear to be confined to the peripheral nervous system (PNS), e.g. facial palsy without overt meningitis symptoms. Unlike blood and intrathecal antibody tests, CSF pleocytosis tests revert to normal after infection ends and therefore can be used as objective markers of treatment success and inform decisions on whether to retreat. In infection involving the PNS, electromyography and nerve conduction studies can be used to monitor objectively the response to treatment. In Lyme carditis, electrocardiograms are used to evidence heart conduction abnormalities, while echocardiography may show myocardial dysfunction. Biopsy and confirmation of Borrelia cells in myocardial tissue may be used in specific cases but are usually not done because of risk of the procedure. Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material ( DNA ) of the Lyme disease spirochete. Culture or PCR are the current means for detecting the presence of the organism, as serologic studies only test for antibodies of Borrelia . PCR has the advantage of being much faster than culture. However, PCR tests are susceptible to false positive results, e.g. by detection of debris of dead Borrelia cells or specimen contamination. Even when properly performed, PCR often shows false-negative results because few Borrelia cells can be found in blood and cerebrospinal fluid (CSF) during infection. Hence, PCR tests are recommended only in special cases, e.g. diagnosis of Lyme arthritis, because it is a highly sensitive way of detecting ospA DNA in synovial fluid. Although sensitivity of PCR in CSF is low, its use may be considered when intrathecal antibody production test results are suspected of being falsely negative, e.g. in very early (< 6 weeks) neuroborreliosis or in immunosuppressed people. Several other forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. OspA antigens , shed by live Borrelia bacteria into urine, are a promising technique being studied. The use of nanotrap particles for their detection is being looked at and the OspA has been linked to active symptoms of Lyme. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. The CDC does not recommend urine antigen tests, PCR tests on urine, immunofluorescent staining for cell-wall-deficient forms of B. burgdorferi , and lymphocyte transformation tests. Neuroimaging is controversial in whether it provides specific patterns unique to neuroborreliosis , but may aid in differential diagnosis and in understanding the pathophysiology of the disease. Though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a person. Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) are two of the tests that can identify abnormalities in the brain of a person affected with this disease. Neuroimaging findings in an MRI include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. The findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. Images produced using SPECT show numerous areas where an insufficient amount of blood is being delivered to the cortex and subcortical white matter. However, SPECT images are known to be nonspecific because they show a heterogeneous pattern in the imaging. The abnormalities seen in the SPECT images are very similar to those seen in people with cerebral vasculitis and Creutzfeldt–Jakob disease , which makes them questionable. Community clinics have been reported to misdiagnose 23–28% of Erythema migrans (EM) rashes and 83% of other objective manifestations of early Lyme disease. EM rashes are often misdiagnosed as spider bites , cellulitis , or shingles . Many misdiagnoses are credited to the widespread misconception that EM rashes should look like a bull's eye. Actually, the key distinguishing features of the EM rash are the speed and extent to which it expands, respectively up to 2–3 cm/day and a diameter of at least 5 cm, and in 50% of cases more than 16 cm. The rash expands away from its center, which may or may not look different or be separated by ring-like clearing from the rest of the rash. Compared to EM rashes, spider bites are more common in the limbs, tend to be more painful and itchy or become swollen, and some may cause necrosis (sinking dark blue patch of dead skin). Cellulitis most commonly develops around a wound or ulcer, is rarely circular, and is more likely to become swollen and tender. EM rashes often appear at sites that are unusual for cellulitis, such as the armpit, groin, abdomen, or back of knee. Like Lyme, shingles often begins with headache, fever, and fatigue, which are followed by pain or numbness. However, unlike Lyme, in shingles these symptoms are usually followed by appearance of rashes composed of multiple small blisters along with a nerve's dermatome , and shingles can also be confirmed by quick laboratory tests. Facial palsy caused by Lyme disease (LDFP) is often misdiagnosed as Bell's palsy . Although Bell's palsy is the most common type of one-sided facial palsy (about 70% of cases), LDFP can account for about 25% of cases of facial palsy in areas where Lyme disease is common. Compared to LDFP, Bell's palsy much less frequently affects both sides of the face. Even though LDFP and Bell's palsy have similar symptoms and evolve similarly if untreated, corticosteroid treatment is beneficial for Bell's Palsy, while being detrimental for LDFP. Recent history of exposure to a likely tick habitat during warmer months, EM rash, viral-like symptoms such as headache and fever, and/or palsy in both sides of the face should be evaluated for the likelihood of LDFP; if it is more than minimal, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease. Unlike viral meningitis , Lyme lymphocytic meningitis tends to not cause fever, last longer, and recur. Lymphocytic meningitis is also characterized by possibly co-occurring with EM rash , facial palsy , or partial vision obstruction and having much lower percentage of polymorphonuclear leukocytes in CSF . Lyme radiculopathy affecting the limbs is often misdiagnosed as a radiculopathy caused by nerve root compression, such as sciatica . Although most cases of radiculopathy are compressive and resolve with conservative treatment (e.g., rest) within 4–6 weeks, guidelines for managing radiculopathy recommend first evaluating risks of other possible causes that, although less frequent, require immediate diagnosis and treatment, including infections such as Lyme and shingles. A history of outdoor activities in likely tick habitats in the last 3 months possibly followed by a rash or viral-like symptoms, and current headache, other symptoms of lymphocytic meningitis, or facial palsy would lead to suspicion of Lyme disease and recommendation of serological and lumbar puncture tests for confirmation. Lyme radiculopathy affecting the trunk can be misdiagnosed as myriad other conditions, such as diverticulitis and acute coronary syndrome . Diagnosis of late-stage Lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call Lyme the new "great imitator". As all people with later-stage infection will have a positive antibody test, simple blood tests can exclude Lyme disease as a possible cause of a person's symptoms. Tick bites may be prevented by avoiding or reducing time in likely tick habitats and taking precautions while in and when getting out of one. Most Lyme human infections are caused by Ixodes nymph bites between April and September. Ticks prefer moist, shaded locations in woodlands , shrubs, tall grasses and leaf litter or wood piles. Tick densities tend to be highest in woodlands, followed by unmaintained edges between woods and lawns (about half as high), ornamental plants and perennial groundcover (about a quarter), and lawns (about 30 times less). Ixodes larvae and nymphs tend to be abundant also where mice nest, such as stone walls and wood logs. Ixodes larvae and nymphs typically wait for potential hosts ("quest") on leaves or grasses close to the ground with forelegs outstretched; when a host brushes against its limbs, the tick rapidly clings and climbs on the host looking for a skin location to bite. In Northeastern United States, 69% of tick bites are estimated to happen in residences, 11% in schools or camps, 9% in parks or recreational areas, 4% at work, 3% while hunting, and 4% in other areas. Activities associated with tick bites around residences include yard work, brush clearing, gardening, playing in the yard, and letting dogs or cats that roam outside in woody or grassy areas into the house. In parks, tick bites often happen while hiking or camping. Walking on a mowed lawn or center of a trail without touching adjacent vegetation is less risky than crawling or sitting on a log or stone wall. Pets should not be allowed to roam freely in likely tick habitats. As a precaution, CDC recommends soaking or spraying clothes, shoes, and camping gear such as tents, backpacks and sleeping bags with 0.5% permethrin solution and hanging them to dry before use. Permethrin is odorless and safe for humans but highly toxic to ticks. After crawling on permethrin-treated fabric for as few as 10–20 seconds, tick nymphs become irritated and fall off or die. Permethrin-treated closed-toed shoes and socks reduce by 74 times the number of bites from nymphs that make first contact with a shoe of a person also wearing treated shorts (because nymphs usually quest near the ground, this is a typical contact scenario). Better protection can be achieved by tucking permethrin-treated trousers (pants) into treated socks and a treated long-sleeve shirt into the trousers so as to minimize gaps through which a tick might reach the wearer's skin. Light-colored clothing may make it easier to see ticks and remove them before they bite. Military and outdoor workers' uniforms treated with permethrin have been found to reduce the number of bite cases by 80–95%. Permethrin protection lasts several weeks of wear and washings in customer-treated items and up to 70 washings for factory-treated items. Permethrin should not be used on human skin, underwear or cats. The EPA recommends several tick repellents for use on exposed skin, including DEET , picaridin , IR3535 (a derivative of amino acid beta-alanine), oil of lemon eucalyptus (OLE, a natural compound) and OLE's active ingredient para-menthane-diol (PMD) . Unlike permethrin, repellents repel but do not kill ticks, protect for only several hours after application, and may be washed off by sweat or water. The most popular repellent is DEET in the U.S. and picaridin in Europe. Unlike DEET, picaridin is odorless and is less likely to irritate the skin or harm fabric or plastics. Repellents with higher concentration may last longer but are not more effective; against ticks, 20% picaridin may work for 8 hours vs. 55–98.11% DEET for 5–6 hours or 30–40% OLE for 6 hours. Repellents should not be used under clothes, on eyes, mouth, wounds or cuts, or on babies younger than 2 months (3 years for OLE or PMD). If sunscreen is used, repellent should be applied on top of it. Repellents should not be sprayed directly on a face, but should instead be sprayed on a hand and then rubbed on the face. After coming indoors, clothes, gear and pets should be checked for ticks. Clothes can be put into a hot dryer for 10 minutes to kill ticks (just washing or warm dryer are not enough). Showering as soon as possible, looking for ticks over the entire body, and removing them reduce risk of infection. Unfed tick nymphs are the size of a poppy seed, but a day or two after biting and attaching themselves to a person, they look like a small blood blister . The following areas should be checked especially carefully: armpits, between legs, back of knee, bellybutton, trunk, and in children ears, neck and hair. Attached ticks should be removed promptly. Risk of infection increases with time of attachment, but in North America risk of Lyme disease is small if the tick is removed within 36 hours. CDC recommends inserting a fine-tipped tweezer between the skin and the tick, grasping very firmly, and pulling the closed tweezer straight away from the skin without twisting, jerking, squeezing or crushing the tick. After tick removal, any tick parts remaining in the skin should be removed with a clean tweezer, if possible. The wound and hands should then be cleaned with alcohol or soap and water. The tick may be disposed by placing it in a container with alcohol, sealed bag, tape or flushed down the toilet. The bitten person should write down where and when the bite happened so that this can be informed to a doctor if the person gets a rash or flu-like symptoms in the following several weeks. CDC recommends not using fingers, nail polish, petroleum jelly or heat on the tick to try to remove it. In Australia, where the Australian paralysis tick is prevalent, the Australasian Society of Clinical Immunology and Allergy recommends not using tweezers to remove ticks, because if the person is allergic, anaphylaxis could result. Instead, a product should be sprayed on the tick to cause it to freeze and then drop off. Another method consists in using about 20 cm of dental floss or fishing line for slowly tying an overhand knot between the skin and the tick and then pulling it away from the skin. The risk of infectious transmission increases with the duration of tick attachment. It requires between 36 and 48 hours of attachment for the bacteria that causes Lyme to travel from within the tick into its saliva. If a deer tick that is sufficiently likely to be carrying Borrelia is found attached to a person and removed, and if the tick has been attached for 36 hours or is engorged, a single dose of doxycycline administered within the 72 hours after removal may reduce the risk of Lyme disease. It is not generally recommended for all people bitten, as development of infection is rare: about 50 bitten people would have to be treated this way to prevent one case of erythema migrans (i.e. the typical rash found in about 70–80% of people infected). Several landscaping practices may reduce the risk of tick bites in residential yards. These include keeping lawns mowed, removing leaf litter and weeds, and avoiding the use of ground cover. A 3-ft-wide rock or woodchip barrier is recommended to separate lawns from wood piles, woodlands , stone walls , and shrubs. Without vegetation on the barrier, ticks will tend not to cross it; acaricides may also be sprayed on it to kill ticks. A sun-exposed tick-safe zone at least 9 ft from the barrier should concentrate human activity on the yard, including any patios, playgrounds and gardening. Materials such as wood decking, concrete, bricks, gravel or woodchips used on the ground under patios and playgrounds would discourage ticks there. An 8-ft-high fence may be added to keep deer away from the tick-safe zone. Outdoor workers are at risk of Lyme disease if they work at sites with infected ticks. This includes construction, landscaping, forestry, brush clearing, land surveying, farming, railroad work, oil field work, utility line work, park or wildlife management. U.S. workers in the northeastern and north-central states are at highest risk of exposure to infected ticks. Ticks may also transmit other tick-borne diseases to workers in these and other regions of the country. Worksites with woods, bushes, high grass or leaf litter are likely to have more ticks. Outdoor workers should be most careful to protect themselves in the late spring and summer when young ticks are most active. Ticks can feed upon the blood of a wide array of possible host species, including lizards , birds , mice , cats , dogs , deer , cattle and humans . The extent to which a tick can feed, reproduce, and spread will depend on the type and availability of its hosts. Whether it will spread disease is also affected by its available hosts. Some species, such as lizards, are referred to as "dilution hosts" because they don't tend to support Lyme disease pathogens and so decrease the likelihood that the disease will be passed on by ticks feeding on them. White-tailed deer are both a food source and a "reproductive host", where ticks tend to mate. The white-footed mouse is a reservoir host in which the pathogen for Lyme disease can survive. Availability of hosts can have significant impacts on the transmission of Lyme disease. A greater diversity of hosts, or of those that don't support the pathogen, tends to decrease the likelihood that the disease will be transmitted. In the United States, one approach to reducing the incidence of Lyme and other deer tick-borne diseases has been to greatly reduce the deer population on which the adult ticks depend for feeding and reproduction. Lyme disease cases fell following deer eradication on an island, Monhegan, Maine , and following deer control in Mumford Cove, Connecticut. Advocates have suggested reducing the deer population to levels of 8 to 10 deer per square mile, compared to levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates. Others have noted that while deer are reproductive hosts, they are not Borrelia burgdorferi reservoirs. Researchers have suggested that smaller, less obviously visible Lyme reservoirs, like white-footed mice and Eastern chipmunks , may more strongly impact Lyme disease occurrence. Ecosystem studies in New York state suggest that white-footed mice thrive when forests are broken into smaller isolated chunks of woodland with fewer rodent predators. With more rodents harboring the disease, the odds increase that a tick will feed on a disease-harboring rodent and that someone will pick up a disease-carrying tick in their garden or walking in the woods. Data indicates that the smaller the wooded area, the more ticks it will contain and the likely they are to carry Lyme disease, supporting the idea that deforestation and habitat fragmentation affect ticks, hosts and disease transmission. Tick-borne diseases are estimated to affect ~80 % of cattle worldwide. They also affect cats, dogs, and other pets. Routine veterinary control of ticks of domestic animals through the use of acaricides has been suggested as a way to reduce exposure of humans to ticks. However, chemical control with acaricides is now criticized on a number of grounds. Ticks appear to develop resistance to acaricides; acaricides are costly; and there are concerns over their toxicity and the potential for chemical residues to affect food and the environment. In Europe, known reservoirs of Borrelia burgdorferi were 9 small mammals, 7 medium-sized mammals and 16 species of birds (including passerines, sea-birds and pheasants). These animals seem to transmit spirochetes to ticks and thus participate in the natural circulation of B. burgdorferi in Europe. The house mouse is also suspected as well as other species of small rodents, particularly in Eastern Europe and Russia. "The reservoir species that contain the most pathogens are the European roe deer Capreolus capreolus ; " it does not appear to serve as a major reservoir of B. burgdorferi " thought Jaenson & al. (1992) (incompetent host for B. burgdorferi and TBE virus) but it is important for feeding the ticks, as red deer and wild boars ( Sus scrofa ), in which one Rickettsia and three Borrelia species were identified", with high risks of coinfection in roe deer. Nevertheless, in the 2000s, in roe deer in Europe " two species of Rickettsia and two species of Borrelia were identified ". Attached ticks should be removed promptly. Risk of infection increases with time of attachment, but in North America risk of Lyme disease is small if the tick is removed within 36 hours. CDC recommends inserting a fine-tipped tweezer between the skin and the tick, grasping very firmly, and pulling the closed tweezer straight away from the skin without twisting, jerking, squeezing or crushing the tick. After tick removal, any tick parts remaining in the skin should be removed with a clean tweezer, if possible. The wound and hands should then be cleaned with alcohol or soap and water. The tick may be disposed by placing it in a container with alcohol, sealed bag, tape or flushed down the toilet. The bitten person should write down where and when the bite happened so that this can be informed to a doctor if the person gets a rash or flu-like symptoms in the following several weeks. CDC recommends not using fingers, nail polish, petroleum jelly or heat on the tick to try to remove it. In Australia, where the Australian paralysis tick is prevalent, the Australasian Society of Clinical Immunology and Allergy recommends not using tweezers to remove ticks, because if the person is allergic, anaphylaxis could result. Instead, a product should be sprayed on the tick to cause it to freeze and then drop off. Another method consists in using about 20 cm of dental floss or fishing line for slowly tying an overhand knot between the skin and the tick and then pulling it away from the skin. The risk of infectious transmission increases with the duration of tick attachment. It requires between 36 and 48 hours of attachment for the bacteria that causes Lyme to travel from within the tick into its saliva. If a deer tick that is sufficiently likely to be carrying Borrelia is found attached to a person and removed, and if the tick has been attached for 36 hours or is engorged, a single dose of doxycycline administered within the 72 hours after removal may reduce the risk of Lyme disease. It is not generally recommended for all people bitten, as development of infection is rare: about 50 bitten people would have to be treated this way to prevent one case of erythema migrans (i.e. the typical rash found in about 70–80% of people infected). Several landscaping practices may reduce the risk of tick bites in residential yards. These include keeping lawns mowed, removing leaf litter and weeds, and avoiding the use of ground cover. A 3-ft-wide rock or woodchip barrier is recommended to separate lawns from wood piles, woodlands , stone walls , and shrubs. Without vegetation on the barrier, ticks will tend not to cross it; acaricides may also be sprayed on it to kill ticks. A sun-exposed tick-safe zone at least 9 ft from the barrier should concentrate human activity on the yard, including any patios, playgrounds and gardening. Materials such as wood decking, concrete, bricks, gravel or woodchips used on the ground under patios and playgrounds would discourage ticks there. An 8-ft-high fence may be added to keep deer away from the tick-safe zone. Outdoor workers are at risk of Lyme disease if they work at sites with infected ticks. This includes construction, landscaping, forestry, brush clearing, land surveying, farming, railroad work, oil field work, utility line work, park or wildlife management. U.S. workers in the northeastern and north-central states are at highest risk of exposure to infected ticks. Ticks may also transmit other tick-borne diseases to workers in these and other regions of the country. Worksites with woods, bushes, high grass or leaf litter are likely to have more ticks. Outdoor workers should be most careful to protect themselves in the late spring and summer when young ticks are most active. Ticks can feed upon the blood of a wide array of possible host species, including lizards , birds , mice , cats , dogs , deer , cattle and humans . The extent to which a tick can feed, reproduce, and spread will depend on the type and availability of its hosts. Whether it will spread disease is also affected by its available hosts. Some species, such as lizards, are referred to as "dilution hosts" because they don't tend to support Lyme disease pathogens and so decrease the likelihood that the disease will be passed on by ticks feeding on them. White-tailed deer are both a food source and a "reproductive host", where ticks tend to mate. The white-footed mouse is a reservoir host in which the pathogen for Lyme disease can survive. Availability of hosts can have significant impacts on the transmission of Lyme disease. A greater diversity of hosts, or of those that don't support the pathogen, tends to decrease the likelihood that the disease will be transmitted. In the United States, one approach to reducing the incidence of Lyme and other deer tick-borne diseases has been to greatly reduce the deer population on which the adult ticks depend for feeding and reproduction. Lyme disease cases fell following deer eradication on an island, Monhegan, Maine , and following deer control in Mumford Cove, Connecticut. Advocates have suggested reducing the deer population to levels of 8 to 10 deer per square mile, compared to levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates. Others have noted that while deer are reproductive hosts, they are not Borrelia burgdorferi reservoirs. Researchers have suggested that smaller, less obviously visible Lyme reservoirs, like white-footed mice and Eastern chipmunks , may more strongly impact Lyme disease occurrence. Ecosystem studies in New York state suggest that white-footed mice thrive when forests are broken into smaller isolated chunks of woodland with fewer rodent predators. With more rodents harboring the disease, the odds increase that a tick will feed on a disease-harboring rodent and that someone will pick up a disease-carrying tick in their garden or walking in the woods. Data indicates that the smaller the wooded area, the more ticks it will contain and the likely they are to carry Lyme disease, supporting the idea that deforestation and habitat fragmentation affect ticks, hosts and disease transmission. Tick-borne diseases are estimated to affect ~80 % of cattle worldwide. They also affect cats, dogs, and other pets. Routine veterinary control of ticks of domestic animals through the use of acaricides has been suggested as a way to reduce exposure of humans to ticks. However, chemical control with acaricides is now criticized on a number of grounds. Ticks appear to develop resistance to acaricides; acaricides are costly; and there are concerns over their toxicity and the potential for chemical residues to affect food and the environment. In Europe, known reservoirs of Borrelia burgdorferi were 9 small mammals, 7 medium-sized mammals and 16 species of birds (including passerines, sea-birds and pheasants). These animals seem to transmit spirochetes to ticks and thus participate in the natural circulation of B. burgdorferi in Europe. The house mouse is also suspected as well as other species of small rodents, particularly in Eastern Europe and Russia. "The reservoir species that contain the most pathogens are the European roe deer Capreolus capreolus ; " it does not appear to serve as a major reservoir of B. burgdorferi " thought Jaenson & al. (1992) (incompetent host for B. burgdorferi and TBE virus) but it is important for feeding the ticks, as red deer and wild boars ( Sus scrofa ), in which one Rickettsia and three Borrelia species were identified", with high risks of coinfection in roe deer. Nevertheless, in the 2000s, in roe deer in Europe " two species of Rickettsia and two species of Borrelia were identified ". As of 2023 [ update ] no human vaccines for Lyme disease were available. The only human vaccine to advance to market was LYMErix, which was available from 1998, but discontinued in 2002. The vaccine candidate VLA15 was scheduled to start a phase 3 trial in the third quarter of 2022, with other research ongoing. Multiple vaccines are available for the prevention of Lyme disease in dogs. The vaccine LYMErix was available from 1998 to 2002. The recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi with aluminum hydroxide as adjuvant, was developed by SmithKline Beecham . In clinical trials involving more than 10,000 people, the vaccine was found to confer protective immunity to Lyme disease in 76% of adults after three doses with only mild or moderate and transient adverse effects . On 21 December 1998, the Food and Drug Administration (FDA) approved LYMErix on the basis of these trials for persons of ages 15 through 70. Following approval of the vaccine , its entry into clinical practice was slow for a variety of reasons, including its cost, which was often not reimbursed by insurance companies. Subsequently, hundreds of vaccine recipients reported they had developed autoimmune and other side effects. Supported by some advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline , alleging the vaccine had caused these health problems. These claims were investigated by the FDA and the Centers for Disease Control, which found no connection between the vaccine and the autoimmune complaints. Despite the lack of evidence that the complaints were caused by the vaccine, sales plummeted and LYMErix was withdrawn from the U.S. market by GlaxoSmithKline in February 2002, in the setting of negative media coverage and fears of vaccine side effects. The fate of LYMErix was described in the medical literature as a "cautionary tale"; an editorial in Nature cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations." The original developer of the OspA vaccine at the Max Planck Institute told Nature : "This just shows how irrational the world can be ... There was no scientific justification for the first OspA vaccine LYMErix being pulled." The hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was developed by Valneva . It was granted fast track designation by the U.S. Food and Drug Administration in July 2017. In April 2020 Pfizer paid $130 million for the rights to the vaccine, and the companies are developing it together, performing multiple phase 2 trials. A phase 3 trial of VLA15 was scheduled for late 2022, recruiting volunteers at test sites located across the northeastern United States and in Europe. Participants were scheduled to receive an initial three-dose series of vaccines over the course of five to nine months, followed by a booster dose after twelve months, with both the initial series and the booster dose scheduled to be complete before the year's peak Lyme disease season. An mRNA vaccine designed to cause a strong fast immune response to tick saliva allowed the immune system to detect and remove the ticks from test animals before they were able to transmit the infectious bacteria. The vaccine contains mRNAs for the body to build 19 proteins in tick saliva which, by enabling quick development of erythema (itchy redness) at the bite site, protects guinea pigs against Lyme disease. It also protected the test animals if the tick is not removed if only one tick, but not three, remain attached. Canine vaccines have been formulated and approved for the prevention of Lyme disease in dogs. Currently, three Lyme disease vaccines are available. LymeVax, formulated by Fort Dodge Laboratories, contains intact dead spirochetes which expose the host to the organism. Galaxy Lyme, Intervet- Schering-Plough 's vaccine, targets proteins OspC and OspA . The OspC antibodies kill any of the bacteria that have not been killed by the OspA antibodies. Canine Recombinant Lyme, formulated by Merial , generates antibodies against the OspA protein so a tick feeding on a vaccinated dog draws in blood full of anti-OspA antibodies, which kill the spirochetes in the tick's gut before they are transmitted to the dog. The vaccine LYMErix was available from 1998 to 2002. The recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi with aluminum hydroxide as adjuvant, was developed by SmithKline Beecham . In clinical trials involving more than 10,000 people, the vaccine was found to confer protective immunity to Lyme disease in 76% of adults after three doses with only mild or moderate and transient adverse effects . On 21 December 1998, the Food and Drug Administration (FDA) approved LYMErix on the basis of these trials for persons of ages 15 through 70. Following approval of the vaccine , its entry into clinical practice was slow for a variety of reasons, including its cost, which was often not reimbursed by insurance companies. Subsequently, hundreds of vaccine recipients reported they had developed autoimmune and other side effects. Supported by some advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline , alleging the vaccine had caused these health problems. These claims were investigated by the FDA and the Centers for Disease Control, which found no connection between the vaccine and the autoimmune complaints. Despite the lack of evidence that the complaints were caused by the vaccine, sales plummeted and LYMErix was withdrawn from the U.S. market by GlaxoSmithKline in February 2002, in the setting of negative media coverage and fears of vaccine side effects. The fate of LYMErix was described in the medical literature as a "cautionary tale"; an editorial in Nature cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations." The original developer of the OspA vaccine at the Max Planck Institute told Nature : "This just shows how irrational the world can be ... There was no scientific justification for the first OspA vaccine LYMErix being pulled." The hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was developed by Valneva . It was granted fast track designation by the U.S. Food and Drug Administration in July 2017. In April 2020 Pfizer paid $130 million for the rights to the vaccine, and the companies are developing it together, performing multiple phase 2 trials. A phase 3 trial of VLA15 was scheduled for late 2022, recruiting volunteers at test sites located across the northeastern United States and in Europe. Participants were scheduled to receive an initial three-dose series of vaccines over the course of five to nine months, followed by a booster dose after twelve months, with both the initial series and the booster dose scheduled to be complete before the year's peak Lyme disease season. An mRNA vaccine designed to cause a strong fast immune response to tick saliva allowed the immune system to detect and remove the ticks from test animals before they were able to transmit the infectious bacteria. The vaccine contains mRNAs for the body to build 19 proteins in tick saliva which, by enabling quick development of erythema (itchy redness) at the bite site, protects guinea pigs against Lyme disease. It also protected the test animals if the tick is not removed if only one tick, but not three, remain attached. Canine vaccines have been formulated and approved for the prevention of Lyme disease in dogs. Currently, three Lyme disease vaccines are available. LymeVax, formulated by Fort Dodge Laboratories, contains intact dead spirochetes which expose the host to the organism. Galaxy Lyme, Intervet- Schering-Plough 's vaccine, targets proteins OspC and OspA . The OspC antibodies kill any of the bacteria that have not been killed by the OspA antibodies. Canine Recombinant Lyme, formulated by Merial , generates antibodies against the OspA protein so a tick feeding on a vaccinated dog draws in blood full of anti-OspA antibodies, which kill the spirochetes in the tick's gut before they are transmitted to the dog. Antibiotics are the primary treatment. The specific approach to their use is dependent on the individual affected and the stage of the disease. For most people with early localized infection, oral administration of doxycycline is widely recommended as the first choice, as it is effective against not only Borrelia bacteria but also a variety of other illnesses carried by ticks. People taking doxycycline should avoid sun exposure because of higher risk of sunburns . Doxycycline is contraindicated in children younger than eight years of age and women who are pregnant or breastfeeding; alternatives to doxycycline are amoxicillin , cefuroxime axetil , and azithromycin . Azithromycin is recommended only in case of intolerance to the other antibiotics. The standard treatment for cellulitis , cephalexin , is not useful for Lyme disease. When it is unclear if a rash is caused by Lyme or cellulitis, the IDSA recommends treatment with cefuroxime or amoxicillin/clavulanic acid , as these are effective against both infections. Individuals with early disseminated or late Lyme infection may have symptomatic cardiac disease, Lyme arthritis, or neurologic symptoms like facial palsy , radiculopathy , meningitis , or peripheral neuropathy . Intravenous administration of ceftriaxone is recommended as the first choice in these cases; cefotaxime and doxycycline are available as alternatives. Treatment regimens for Lyme disease range from 14 days in early localized disease, to 14–21 days in early disseminated disease to 14–28 days in late disseminated disease. Neurologic complications of Lyme disease may be treated with doxycycline as it can be taken by mouth and has a lower cost, although in North America evidence of efficacy is only indirect. In case of failure, guidelines recommend retreatment with injectable ceftriaxone . Several months after treatment for Lyme arthritis, if joint swelling persists or returns, a second round of antibiotics may be considered; intravenous antibiotics are preferred for retreatment in case of poor response to oral antibiotics. Outside of that, a prolonged antibiotic regimen lasting more than 28 days is not recommended as no evidence shows it to be effective. IgM and IgG antibody levels may be elevated for years even after successful treatment with antibiotics. As antibody levels are not indicative of treatment success, testing for them is not recommended. Facial palsy may resolve without treatment; however, antibiotic treatment is recommended to stop other Lyme complications. Corticosteroids are not recommended when facial palsy is caused by Lyme disease. In those with facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping. About a third of people with Lyme carditis need a temporary pacemaker until their heart conduction abnormality resolves, and 21% need to be hospitalized. Lyme carditis should not be treated with corticosteroids. People with Lyme arthritis should limit their level of physical activity to avoid damaging affected joints, and in case of limping should use crutches. Pain associated with Lyme disease may be treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroid joint injections are not recommended for Lyme arthritis that is being treated with antibiotics. People with Lyme arthritis treated with intravenous antibiotics or two months of oral antibiotics who continue to have joint swelling two months after treatment and have negative PCR test for Borrelia DNA in the synovial fluid are said to have post-antibiotic Lyme arthritis; this is more common after infection by certain Borrelia strains in people with certain genetic and immunologic characteristics. Post-antibiotic Lyme arthritis may be symptomatically treated with NSAIDs, disease-modifying antirheumatic drugs (DMARDs), arthroscopic synovectomy , or physical therapy. People receiving treatment should be advised that reinfection is possible and how to prevent it . Lyme disease's typical first sign, the erythema migrans (EM) rash, resolves within several weeks even without treatment. However, in untreated people, the infection often disseminates to the nervous system, heart, or joints, possibly causing permanent damage to body tissues. People who receive recommended antibiotic treatment within several days of appearance of an initial EM rash have the best prospects. Recovery may not be total or immediate. The percentage of people achieving full recovery in the United States increases from about 64–71% at end of treatment for EM rash to about 84–90% after 30 months; higher percentages are reported in Europe. Treatment failure, i.e. persistence of original or appearance of new signs of the disease, occurs only in a few people. Remaining people are considered cured but continue to experience subjective symptoms, e.g. joint or muscle pains or fatigue . These symptoms usually are mild and nondisabling. People treated only after nervous system manifestations of the disease may end up with objective neurological deficits, in addition to subjective symptoms. In Europe, an average of 32–33 months after initial Lyme symptoms in people treated mostly with doxycycline 200 mg for 14–21 days, the percentage of people with lingering symptoms was much higher among those diagnosed with neuroborreliosis (50%) than among those with only an EM rash (16%). In another European study, 5 years after treatment for neuroborreliosis, lingering symptoms were less common among children (15%) than adults (30%), and in the latter was less common among those treated within 30 days of the first symptom (16%) than among those treated later (39%); among those with lingering symptoms, 54% had daily activities restricted and 19% were on sick leave or incapacitated. Some data suggest that about 90% of Lyme facial palsies treated with antibiotics recover fully a median of 24 days after appearing and most of the rest recover with only mild abnormality. However, in Europe 41% of people treated for facial palsy had other lingering symptoms at followup up to 6 months later, including 28% with numbness or altered sensation and 14% with fatigue or concentration problems. Palsies in both sides of the face are associated with worse and longer time to recovery. Historical data suggests that untreated people with facial palsies recover at nearly the same rate, but 88% subsequently have Lyme arthritis. Other research shows that synkinesis (involuntary movement of a facial muscle when another one is voluntarily moved) can become evident only 6–12 months after facial palsy appears to be resolved, as damaged nerves regrow and sometimes connect to incorrect muscles. Synkinesis is associated with corticosteroid use. In longer-term follow-up, 16–23% of Lyme facial palsies do not fully recover. In Europe, about a quarter of people with Bannwarth syndrome (Lyme radiculopathy and lymphocytic meningitis ) treated with intravenous ceftriaxone for 14 days an average of 30 days after first symptoms had to be retreated 3–6 months later because of unsatisfactory clinical response or continued objective markers of infection in cerebrospinal fluid ; after 12 months, 64% recovered fully, 31% had nondisabling mild or infrequent symptoms that did not require regular use of analgesics, and 5% had symptoms that were disabling or required substantial use of analgesics. The most common lingering nondisabling symptoms were headache, fatigue , altered sensation , joint pains , memory disturbances, malaise , radicular pain , sleep disturbances, muscle pains , and concentration disturbances. Lingering disabling symptoms included facial palsy and other impaired movement . Recovery from late neuroborreliosis tends to take longer and be less complete than from early neuroborreliosis, probably because of irreversible neurologic damage. About half the people with Lyme carditis progress to complete heart block , but it usually resolves in a week. Other Lyme heart conduction abnormalities resolve typically within 6 weeks. About 94% of people have full recovery, but 5% need a permanent pacemaker and 1% end up with persistent heart block (the actual percentage may be higher because of unrecognized cases). Lyme myocardial complications usually are mild and self-limiting. However, in some cases Lyme carditis can be fatal. Recommended antibiotic treatments are effective in about 90% of Lyme arthritis cases, although it can take several months for inflammation to resolve and a second round of antibiotics is often necessary. Antibiotic-refractory Lyme arthritis also eventually resolves, typically within 9–14 months (range 4 months – 4 years); DMARDs or synovectomy can accelerate recovery. Reinfection is not uncommon. In a U.S. study, 6–11% of people treated for an EM rash had another EM rash within 30 months. The second rash typically is due to infection by a different Borrelia strain. Chronic symptoms like pain, fatigue, or cognitive impairment are experienced by 10 – 20% of people who contract Lyme disease, even after completing treatment. This is called Post-treatment Lyme disease syndrome, or PTLDS. The cause is unknown. One hypothesis is that a persistent, difficult-to-detect infection remains. Work with mice, dogs, and non-human primates have shown evidence of persistent B. burgdorferi , although these remaining bacteria are hard to cultivate and Koch's postulates are hard to prove. Another hypothesis is that autoimmunity has been triggered by the infection. Auto–immune responses are known to occur following other infections, including Campylobacter ( Guillain-Barré syndrome ), Chlamydia (reactive arthritis), and strep throat (rheumatic heart disease). A third hypothesis is that symptoms are simply unrelated to the previous Lyme infection. There is no proven treatment for Post-treatment Lyme disease syndrome. While short-term antibiotics are effective in early Lyme disease, prolonged antibiotics are not. They have been shown ineffective in placebo-controlled trials and carry the risk of serious, sometimes deadly complications. Generally, treatment is symptomatic and is similar to the management of fibromyalgia or ME/CFS . PTLDS usually gets better over time, but recovery may take many months. Chronic symptoms like pain, fatigue, or cognitive impairment are experienced by 10 – 20% of people who contract Lyme disease, even after completing treatment. This is called Post-treatment Lyme disease syndrome, or PTLDS. The cause is unknown. One hypothesis is that a persistent, difficult-to-detect infection remains. Work with mice, dogs, and non-human primates have shown evidence of persistent B. burgdorferi , although these remaining bacteria are hard to cultivate and Koch's postulates are hard to prove. Another hypothesis is that autoimmunity has been triggered by the infection. Auto–immune responses are known to occur following other infections, including Campylobacter ( Guillain-Barré syndrome ), Chlamydia (reactive arthritis), and strep throat (rheumatic heart disease). A third hypothesis is that symptoms are simply unrelated to the previous Lyme infection. There is no proven treatment for Post-treatment Lyme disease syndrome. While short-term antibiotics are effective in early Lyme disease, prolonged antibiotics are not. They have been shown ineffective in placebo-controlled trials and carry the risk of serious, sometimes deadly complications. Generally, treatment is symptomatic and is similar to the management of fibromyalgia or ME/CFS . PTLDS usually gets better over time, but recovery may take many months. Lyme disease occurs regularly in Northern Hemisphere temperate regions. An estimated 476,000 people a year are diagnosed and treated for the disease in the United States. This number is likely an overestimate due to overdiagnosis and overtreatment. Over 200,000 people a year are diagnosed and treated in Europe. There is a suggestion that tick populations and Lyme disease occurrence are increasing and spreading into new areas, due in part to the warming temperatures of climate change . However, tick-borne disease systems are complex, and determining whether changes are due to climate change or other drivers can be difficult. Lyme disease effects are comparable among males and females. A wide range of age groups is affected, though the number of cases is highest among 10- to 19-year-olds. In northern Africa, B. burgdorferi sensu lato has been identified in Morocco , Algeria , Egypt and Tunisia . Lyme disease in sub-Saharan Africa is presently unknown, but evidence indicates it may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa. In East Africa, two cases of Lyme disease have been reported in Kenya . According The Federation of Infectious Diseases Societies of Southern Africa, Lyme disease is not known to be endemic in either South Africa or Mozambique. B. burgdorferi sensu lato -infested ticks are being found more frequently in Japan, as well as in northwest China, Nepal , Thailand and far eastern Russia. Borrelia has also been isolated in Mongolia . Lyme disease is not considered endemic to Australia. While there have been reports of people acquiring Lyme disease in Australia, and even evidence of closely related Borrelia species in ticks, the evidence linking these cases to local transmission is limited. Ongoing research on resolving potential Borrelia species to Debilitating Symptom Complexes Attributed to Ticks (DSCATT) in Australia are ongoing. In Europe, Lyme disease is caused by infection with one or more pathogenic European genospecies of the spirochaete B. burgdorferi sensu lato , mainly transmitted by the tick Ixodes ricinus . Cases of B. burgdorferi sensu lato -infected ticks are found predominantly in central Europe, particularly in Slovenia and Austria, but have been isolated in almost every country on the continent. Number of cases in southern Europe, such as Italy and Portugal, is much lower. Diagnosed cases in some Western countries, such as Iceland, are rising. Lyme disease is rare in Iceland. On average around 6 to 7 cases are diagnosed every year, primarily localised infections presenting as erythema migrans. None of the cases had a definitive Icelandic origin and the yearly number of cases has not been increasing. In the United Kingdom the number of laboratory-confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986 when 68 cases were recorded in the UK and Ireland combined. In the UK there were 23 confirmed cases in 1988 and 19 in 1990, but 973 in 2009 and 953 in 2010. Provisional figures for the first 3 quarters of 2011 show a 26% increase on the same period in 2010. It is thought, however, that the actual number of cases is significantly higher than suggested by the above figures, with the UK's Health Protection Agency estimating that there are between 2,000 and 3,000 cases per year, (with an average of around 15% of the infections acquired overseas ), while Dr Darrel Ho-Yen, Director of the Scottish Toxoplasma Reference Laboratory and National Lyme Disease Testing Service, believes that the number of confirmed cases should be multiplied by 10 "to take account of wrongly diagnosed cases, tests giving false results, sufferers who weren't tested, people who are infected but not showing symptoms, failures to notify and infected individuals who don't consult a doctor." Despite Lyme disease ( Borrelia burgdorferi infection) being a notifiable disease in Scotland since January 1990 which should therefore be reported on the basis of clinical suspicion, it is believed that many GPs are unaware of the requirement. Mandatory reporting, limited to laboratory test results only, was introduced throughout the UK in October 2010, under the Health Protection (Notification) Regulations 2010. Although there is a greater number of cases of Lyme disease in the New Forest , Salisbury Plain , Exmoor , the South Downs , parts of Wiltshire and Berkshire , Thetford Forest and the West coast and islands of Scotland, infected ticks are widespread, and can even be found in the parks of London. A 1989 report found that 25% of forestry workers in the New Forest were seropositive , as were between 2% and 4–5% of the general local population of the area. Tests on pet dogs carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought. It is speculated that global warming may lead to an increase in tick activity in the future, as well as an increase in the amount of time that people spend in public parks, thus increasing the risk of infection. However no published research has proven this to be so. Many studies in North America have examined ecological and environmental correlates of the number of people affected by Lyme disease. A 2005 study using climate suitability modelling of I. scapularis projected that climate change would cause an overall 213% increase in suitable vector habitat by 2080, with northward expansions in Canada, increased suitability in the central U.S., and decreased suitable habitat and vector retraction in the southern U.S. A 2008 review of published studies concluded that the presence of forests or forested areas was the only variable that consistently elevated the risk of Lyme disease whereas other environmental variables showed little or no concordance between studies. The authors argued that the factors influencing tick density and human risk between sites are still poorly understood, and that future studies should be conducted over longer time periods, become more standardized across regions, and incorporate existing knowledge of regional Lyme disease ecology . The range of ticks able to carry Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, southern New Brunswick, southwest Nova Scotia and limited parts of Saskatchewan and Alberta, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland. A model-based prediction by Leighton et al. (2012) suggests that the range of the I. scapularis tick will expand into Canada by 46 km/year over the next decade, with warming climatic temperatures as the main driver of increased speed of spread. A 2007 study suggests Borrelia burgdorferi infections are endemic to Mexico, from four cases reported between 1999 and 2000. Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005. Although Lyme disease has been reported in all states due to travel-associated infections, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central). CDC implemented national surveillance of Lyme disease cases in 1991. Since then, reporting criteria has been modified multiple times. The 2022 surveillance case definition classifies cases as confirmed, probable, and suspect. The number of reported cases of the disease has been increasing, as are endemic regions in North America. The CDC emphasizes that, while surveillance data has limitations, it is useful due to "uniformity, simplicity, and timeliness." While cases are under-reported in high-incidence areas, over-reporting is likely in low-incidence areas. Additionally, surveillance cases are reported by county of residence and not where an infection was necessarily contracted. Several similar but apparently distinct conditions may exist, caused by various species or subspecies of Borrelia in North America. A regionally restricted condition that may be related to Borrelia infection is southern tick-associated rash illness (STARI), also known as Masters disease. Amblyomma americanum , known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so people in these regions experiencing Lyme-like symptoms—especially if they follow a bite from a lone-star tick—should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment. In recent years there have been 5 to 10 cases a year of a disease similar to Lyme occurring in Montana. It occurs primarily in pockets along the Yellowstone River in central Montana. People have developed a red bull's-eye rash around a tick bite followed by weeks of fatigue and a fever. In Brazil, a Lyme-like disease known as Baggio–Yoshinari syndrome was identified, caused by microorganisms that do not belong to the B. burgdorferi sensu lato complex and transmitted by ticks of the Amblyomma and Rhipicephalus genera. The first reported case of BYS in Brazil was made in 1992 in Cotia , São Paulo. In northern Africa, B. burgdorferi sensu lato has been identified in Morocco , Algeria , Egypt and Tunisia . Lyme disease in sub-Saharan Africa is presently unknown, but evidence indicates it may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa. In East Africa, two cases of Lyme disease have been reported in Kenya . According The Federation of Infectious Diseases Societies of Southern Africa, Lyme disease is not known to be endemic in either South Africa or Mozambique. B. burgdorferi sensu lato -infested ticks are being found more frequently in Japan, as well as in northwest China, Nepal , Thailand and far eastern Russia. Borrelia has also been isolated in Mongolia . Lyme disease is not considered endemic to Australia. While there have been reports of people acquiring Lyme disease in Australia, and even evidence of closely related Borrelia species in ticks, the evidence linking these cases to local transmission is limited. Ongoing research on resolving potential Borrelia species to Debilitating Symptom Complexes Attributed to Ticks (DSCATT) in Australia are ongoing. In Europe, Lyme disease is caused by infection with one or more pathogenic European genospecies of the spirochaete B. burgdorferi sensu lato , mainly transmitted by the tick Ixodes ricinus . Cases of B. burgdorferi sensu lato -infected ticks are found predominantly in central Europe, particularly in Slovenia and Austria, but have been isolated in almost every country on the continent. Number of cases in southern Europe, such as Italy and Portugal, is much lower. Diagnosed cases in some Western countries, such as Iceland, are rising. Lyme disease is rare in Iceland. On average around 6 to 7 cases are diagnosed every year, primarily localised infections presenting as erythema migrans. None of the cases had a definitive Icelandic origin and the yearly number of cases has not been increasing. In the United Kingdom the number of laboratory-confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986 when 68 cases were recorded in the UK and Ireland combined. In the UK there were 23 confirmed cases in 1988 and 19 in 1990, but 973 in 2009 and 953 in 2010. Provisional figures for the first 3 quarters of 2011 show a 26% increase on the same period in 2010. It is thought, however, that the actual number of cases is significantly higher than suggested by the above figures, with the UK's Health Protection Agency estimating that there are between 2,000 and 3,000 cases per year, (with an average of around 15% of the infections acquired overseas ), while Dr Darrel Ho-Yen, Director of the Scottish Toxoplasma Reference Laboratory and National Lyme Disease Testing Service, believes that the number of confirmed cases should be multiplied by 10 "to take account of wrongly diagnosed cases, tests giving false results, sufferers who weren't tested, people who are infected but not showing symptoms, failures to notify and infected individuals who don't consult a doctor." Despite Lyme disease ( Borrelia burgdorferi infection) being a notifiable disease in Scotland since January 1990 which should therefore be reported on the basis of clinical suspicion, it is believed that many GPs are unaware of the requirement. Mandatory reporting, limited to laboratory test results only, was introduced throughout the UK in October 2010, under the Health Protection (Notification) Regulations 2010. Although there is a greater number of cases of Lyme disease in the New Forest , Salisbury Plain , Exmoor , the South Downs , parts of Wiltshire and Berkshire , Thetford Forest and the West coast and islands of Scotland, infected ticks are widespread, and can even be found in the parks of London. A 1989 report found that 25% of forestry workers in the New Forest were seropositive , as were between 2% and 4–5% of the general local population of the area. Tests on pet dogs carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought. It is speculated that global warming may lead to an increase in tick activity in the future, as well as an increase in the amount of time that people spend in public parks, thus increasing the risk of infection. However no published research has proven this to be so.In the United Kingdom the number of laboratory-confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986 when 68 cases were recorded in the UK and Ireland combined. In the UK there were 23 confirmed cases in 1988 and 19 in 1990, but 973 in 2009 and 953 in 2010. Provisional figures for the first 3 quarters of 2011 show a 26% increase on the same period in 2010. It is thought, however, that the actual number of cases is significantly higher than suggested by the above figures, with the UK's Health Protection Agency estimating that there are between 2,000 and 3,000 cases per year, (with an average of around 15% of the infections acquired overseas ), while Dr Darrel Ho-Yen, Director of the Scottish Toxoplasma Reference Laboratory and National Lyme Disease Testing Service, believes that the number of confirmed cases should be multiplied by 10 "to take account of wrongly diagnosed cases, tests giving false results, sufferers who weren't tested, people who are infected but not showing symptoms, failures to notify and infected individuals who don't consult a doctor." Despite Lyme disease ( Borrelia burgdorferi infection) being a notifiable disease in Scotland since January 1990 which should therefore be reported on the basis of clinical suspicion, it is believed that many GPs are unaware of the requirement. Mandatory reporting, limited to laboratory test results only, was introduced throughout the UK in October 2010, under the Health Protection (Notification) Regulations 2010. Although there is a greater number of cases of Lyme disease in the New Forest , Salisbury Plain , Exmoor , the South Downs , parts of Wiltshire and Berkshire , Thetford Forest and the West coast and islands of Scotland, infected ticks are widespread, and can even be found in the parks of London. A 1989 report found that 25% of forestry workers in the New Forest were seropositive , as were between 2% and 4–5% of the general local population of the area. Tests on pet dogs carried out throughout the country in 2009 indicated that around 2.5% of ticks in the UK may be infected, considerably higher than previously thought. It is speculated that global warming may lead to an increase in tick activity in the future, as well as an increase in the amount of time that people spend in public parks, thus increasing the risk of infection. However no published research has proven this to be so.Many studies in North America have examined ecological and environmental correlates of the number of people affected by Lyme disease. A 2005 study using climate suitability modelling of I. scapularis projected that climate change would cause an overall 213% increase in suitable vector habitat by 2080, with northward expansions in Canada, increased suitability in the central U.S., and decreased suitable habitat and vector retraction in the southern U.S. A 2008 review of published studies concluded that the presence of forests or forested areas was the only variable that consistently elevated the risk of Lyme disease whereas other environmental variables showed little or no concordance between studies. The authors argued that the factors influencing tick density and human risk between sites are still poorly understood, and that future studies should be conducted over longer time periods, become more standardized across regions, and incorporate existing knowledge of regional Lyme disease ecology . The range of ticks able to carry Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, southern New Brunswick, southwest Nova Scotia and limited parts of Saskatchewan and Alberta, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland. A model-based prediction by Leighton et al. (2012) suggests that the range of the I. scapularis tick will expand into Canada by 46 km/year over the next decade, with warming climatic temperatures as the main driver of increased speed of spread. A 2007 study suggests Borrelia burgdorferi infections are endemic to Mexico, from four cases reported between 1999 and 2000. Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005. Although Lyme disease has been reported in all states due to travel-associated infections, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central). CDC implemented national surveillance of Lyme disease cases in 1991. Since then, reporting criteria has been modified multiple times. The 2022 surveillance case definition classifies cases as confirmed, probable, and suspect. The number of reported cases of the disease has been increasing, as are endemic regions in North America. The CDC emphasizes that, while surveillance data has limitations, it is useful due to "uniformity, simplicity, and timeliness." While cases are under-reported in high-incidence areas, over-reporting is likely in low-incidence areas. Additionally, surveillance cases are reported by county of residence and not where an infection was necessarily contracted. Several similar but apparently distinct conditions may exist, caused by various species or subspecies of Borrelia in North America. A regionally restricted condition that may be related to Borrelia infection is southern tick-associated rash illness (STARI), also known as Masters disease. Amblyomma americanum , known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so people in these regions experiencing Lyme-like symptoms—especially if they follow a bite from a lone-star tick—should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment. In recent years there have been 5 to 10 cases a year of a disease similar to Lyme occurring in Montana. It occurs primarily in pockets along the Yellowstone River in central Montana. People have developed a red bull's-eye rash around a tick bite followed by weeks of fatigue and a fever. The range of ticks able to carry Lyme disease has expanded from a limited area of Ontario to include areas of southern Quebec, Manitoba, northern Ontario, southern New Brunswick, southwest Nova Scotia and limited parts of Saskatchewan and Alberta, as well as British Columbia. Cases have been reported as far east as the island of Newfoundland. A model-based prediction by Leighton et al. (2012) suggests that the range of the I. scapularis tick will expand into Canada by 46 km/year over the next decade, with warming climatic temperatures as the main driver of increased speed of spread. A 2007 study suggests Borrelia burgdorferi infections are endemic to Mexico, from four cases reported between 1999 and 2000. Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005. Although Lyme disease has been reported in all states due to travel-associated infections, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central). CDC implemented national surveillance of Lyme disease cases in 1991. Since then, reporting criteria has been modified multiple times. The 2022 surveillance case definition classifies cases as confirmed, probable, and suspect. The number of reported cases of the disease has been increasing, as are endemic regions in North America. The CDC emphasizes that, while surveillance data has limitations, it is useful due to "uniformity, simplicity, and timeliness." While cases are under-reported in high-incidence areas, over-reporting is likely in low-incidence areas. Additionally, surveillance cases are reported by county of residence and not where an infection was necessarily contracted. Several similar but apparently distinct conditions may exist, caused by various species or subspecies of Borrelia in North America. A regionally restricted condition that may be related to Borrelia infection is southern tick-associated rash illness (STARI), also known as Masters disease. Amblyomma americanum , known commonly as the lone-star tick, is recognized as the primary vector for STARI. In some parts of the geographical distribution of STARI, Lyme disease is quite rare (e.g., Arkansas), so people in these regions experiencing Lyme-like symptoms—especially if they follow a bite from a lone-star tick—should consider STARI as a possibility. It is generally a milder condition than Lyme and typically responds well to antibiotic treatment. In recent years there have been 5 to 10 cases a year of a disease similar to Lyme occurring in Montana. It occurs primarily in pockets along the Yellowstone River in central Montana. People have developed a red bull's-eye rash around a tick bite followed by weeks of fatigue and a fever. In Brazil, a Lyme-like disease known as Baggio–Yoshinari syndrome was identified, caused by microorganisms that do not belong to the B. burgdorferi sensu lato complex and transmitted by ticks of the Amblyomma and Rhipicephalus genera. The first reported case of BYS in Brazil was made in 1992 in Cotia , São Paulo. Lyme disease was diagnosed as a separate condition for the first time in 1975 in Lyme, Connecticut . The evolutionary history of Borrelia burgdorferi genetics has been the subject of recent studies. One study has found that prior to the reforestation that accompanied post-colonial farm abandonment in New England and the wholesale migration into the mid-west that occurred during the early 19th century, Lyme disease was present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest. John Josselyn, who visited New England in 1638 and again from 1663 to 1670, wrote "there be infinite numbers of ticks hanging upon the bushes in summertime that will cleave to man's garments and creep into his breeches, eating themselves in a short time into the very flesh of a man. I have seen the stockings of those that have gone through the woods covered with them." This is also confirmed by the writings of Peter Kalm , a Swedish botanist who was sent to America by Linnaeus , and who found the forests of New York "abound" with ticks when he visited in 1749. When Kalm's journey was retraced 100 years later, the forests were gone and the Lyme bacterium had probably become isolated to a few pockets along the northeast coast, Wisconsin, and Minnesota. Perhaps the first detailed description of what is now known as Lyme disease appeared in the writings of John Walker after a visit to the island of Jura (Deer Island) off the west coast of Scotland in 1764. He gives a good description both of the symptoms of Lyme disease (with "exquisite pain [in] the interior parts of the limbs") and of the tick vector itself, which he describes as a "worm" with a body which is "of a reddish color and of a compressed shape with a row of feet on each side" that "penetrates the skin". Many people from this area of Great Britain emigrated to North America between 1717 and the end of the 18th century. [ citation needed ] The examination of preserved museum specimens has found Borrelia DNA in an infected Ixodes ricinus tick from Germany that dates back to 1884, and from an infected mouse from Cape Cod that died in 1894. The 2010 autopsy of Ötzi the Iceman , a 5,300-year-old mummy , revealed the presence of the DNA sequence of Borrelia burgdorferi making him the earliest known human with Lyme disease. The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Breslau , Germany (now Wrocław , Poland), where physician Alfred Buchwald described a man who for 16 years had had a degenerative skin disorder now known as acrodermatitis chronica atrophicans . At a 1909 research conference, Swedish dermatologist Arvid Afzelius presented a study about an expanding, ring-like lesion he had observed in an older woman following the bite of a sheep tick. He named the lesion erythema migrans . The skin condition now known as borrelial lymphocytoma was first described in 1911. The modern history of medical understanding of the disease, including its cause, diagnosis, and treatment, has been difficult. Neurological problems following tick bites were recognized starting in the 1920s. French physicians Garin and Bujadoux described a farmer with a painful sensory radiculitis accompanied by mild meningitis following a tick bite. A large, ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. In 1930, the Swedish dermatologist Sven Hellerström was the first to propose EM and neurological symptoms following a tick bite were related. In the 1940s, German neurologist Alfred Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions. Carl Lennhoff, who worked at the Karolinska Institute in Sweden, believed many skin conditions were caused by spirochetes. In 1948, he used a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM. Although his conclusions were later shown to be erroneous, interest in the study of spirochetes was sparked. In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin. In the 1950s, the relationship among tick bite, lymphocytoma, EM and Bannwarth's syndrome was recognized throughout Europe leading to the widespread use of penicillin for treatment in Europe. In 1970, a dermatologist in Wisconsin named Rudolph Scrimenti recognized an EM lesion in a person after recalling a paper by Hellerström that had been reprinted in an American science journal in 1950. This was the first documented case of EM in the United States. Based on the European literature, he treated the person with penicillin. The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns Lyme and Old Lyme , which gave the disease its popular name. This was investigated by physicians David Snydman and Allen Steere of the Epidemic Intelligence Service , and by others from Yale University , including Stephen Malawista , who is credited as a co-discover of the disease. The recognition that the people in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe. Before 1976, the elements of B. burgdorferi sensu lato infection were called or known as tick-borne meningopolyneuritis, Garin-Bujadoux syndrome, Bannwarth syndrome, Afzelius's disease, Montauk Knee or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease, Lyme borreliosis or simply borreliosis. In 1980, Steere, et al. , began to test antibiotic regimens in adults with Lyme disease. In the same year, New York State Health Dept. epidemiologist Jorge Benach provided Willy Burgdorfer , a researcher at the Rocky Mountain Biological Laboratory , with collections of I. dammini [ scapularis ] from Shelter Island, New York, a known Lyme-endemic area as part of an ongoing investigation of Rocky Mountain spotted fever. In examining the ticks for rickettsiae, Burgdorfer noticed "poorly stained, rather long, irregularly coiled spirochetes." Further examination revealed spirochetes in 60% of the ticks. Burgdorfer credited his familiarity with the European literature for his realization that the spirochetes might be the "long-sought cause of ECM and Lyme disease." Benach supplied him with more ticks from Shelter Island and sera from people diagnosed with Lyme disease. University of Texas Health Science Center researcher Alan Barbour "offered his expertise to culture and immunochemically characterize the organism." Burgdorfer subsequently confirmed his discovery by isolating, from people with Lyme disease, spirochetes identical to those found in ticks. In June 1982, he published his findings in Science , and the spirochete was named Borrelia burgdorferi in his honor. After the identification of B. burgdorferi as the causative agent of Lyme disease, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics , amoxicillin , cefuroxime axetil , intravenous and intramuscular penicillin and intravenous ceftriaxone . The mechanism of tick transmission was also the subject of much discussion. B. burgdorferi spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands. Landscape changes & urbanization Urbanization and other anthropogenic factors can be implicated in the spread of Lyme disease to humans. In many areas, expansion of suburban neighborhoods has led to gradual deforestation of surrounding wooded areas and increased border contact between humans and tick-dense areas. Human expansion has also resulted in a reduction of predators that hunt deer as well as mice, chipmunks and other small rodents—the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector , the likelihood of transmission of the disease has greatly increased. Researchers are investigating possible links between global warming and the spread of vector-borne diseases, including Lyme disease. The dilution effect Given these habitat-host dynamics, some researchers have begun to postulate whether the dilution effect could mitigate the spread of Lyme disease. The dilution effect is a hypothesis that predicts that an increase in host biodiversity will result in a decrease in the number of vectors infected with B. burgdorferi . Scientific research has shown that nymphal infection prevalence (NIP) decreases as the number of host species increases, supporting the dilution effect. That said, these findings should not be misinterpreted to suggest that there is a direct relationship between decreased NIP and decreased epidemiological risk, as this has yet to be proven. Additionally, it is important to note that, thus far, the dilution effect is only supported in the Northeastern United States, and has been disproved in other parts of the world that also experience high Lyme disease incidence rates Chronic Lyme disease The term "chronic Lyme disease" is controversial and not recognized in the medical literature, and most medical authorities advise against long-term antibiotic treatment for Lyme disease. Studies have shown that most people diagnosed with "chronic Lyme disease" either have no objective evidence of previous or current infection with B. burgdorferi or are people who should be classified as having post-treatment Lyme disease syndrome (PTLDS), which is defined as continuing or relapsing non-specific symptoms (such as fatigue, musculoskeletal pain, and cognitive complaints) in a person previously treated for Lyme disease. The 2008 documentary Under Our Skin is known for promoting controversial and unrecognized theories about "chronic Lyme disease". Prevention of Lyme disease is an important step in keeping dogs safe in endemic areas. Prevention education and a number of preventive measures are available. First, for dog owners who live near or who often frequent tick-infested areas, routine vaccinations of their dogs is an important step. Another crucial preventive measure is the use of persistent acaricides, such as topical repellents or pesticides that contain triazapentadienes ( Amitraz ), phenylpyrazoles ( Fipronil ), or permethrin ( pyrethroids ). These acaricides target primarily the adult stages of Lyme-carrying ticks and reduce the number of reproductively active ticks in the environment. Formulations of these ingredients are available in a variety of topical forms, including spot-ons, sprays, powders, impregnated collars, solutions, and shampoos. Examination of a dog for ticks after being in a tick-infested area is an important precautionary measure to take in the prevention of Lyme disease. Key spots to examine include the head, neck, and ears. In dogs, a serious long-term prognosis may result in glomerular disease, which is a category of kidney damage that may cause chronic kidney disease. Dogs may also experience chronic joint disease if the disease is left untreated. However, the majority of cases of Lyme disease in dogs result in complete recovery with, and sometimes without, treatment with antibiotics. [ verification needed ] In rare cases, Lyme disease can be fatal to both humans and dogs. Unlike dogs, it is very rare for a cat to be infected with Lyme disease. However, cats are nevertheless capable of being infected with B. burgdorferi , following a bite from an infected tick. Cats who are infected with Lyme Disease may show symptoms including but not limited to lameness, fatigue, or loss of appetite. In two cases, the infected cats experienced cardiac irregularities similar to symptoms of Lyme in both dogs and humans. However, cats who are infected with Lyme disease are likely to be asymptomatic , and show no noticeable signs of the disease. Cats with Lyme are often treated with antibiotics, much like other animals. In some cases, additional treatment or therapy may be required. While Lyme disease can occur in horses, not every infection with B. burgdorferi is associated with symptoms. Especially, detection of specific antibodies against B. burgdorferi alone is not sufficient for a diagnosis of equine Lyme disease and unspecific testing for antibodies is not recommended. Prevention of Lyme disease is an important step in keeping dogs safe in endemic areas. Prevention education and a number of preventive measures are available. First, for dog owners who live near or who often frequent tick-infested areas, routine vaccinations of their dogs is an important step. Another crucial preventive measure is the use of persistent acaricides, such as topical repellents or pesticides that contain triazapentadienes ( Amitraz ), phenylpyrazoles ( Fipronil ), or permethrin ( pyrethroids ). These acaricides target primarily the adult stages of Lyme-carrying ticks and reduce the number of reproductively active ticks in the environment. Formulations of these ingredients are available in a variety of topical forms, including spot-ons, sprays, powders, impregnated collars, solutions, and shampoos. Examination of a dog for ticks after being in a tick-infested area is an important precautionary measure to take in the prevention of Lyme disease. Key spots to examine include the head, neck, and ears. In dogs, a serious long-term prognosis may result in glomerular disease, which is a category of kidney damage that may cause chronic kidney disease. Dogs may also experience chronic joint disease if the disease is left untreated. However, the majority of cases of Lyme disease in dogs result in complete recovery with, and sometimes without, treatment with antibiotics. [ verification needed ] In rare cases, Lyme disease can be fatal to both humans and dogs. Unlike dogs, it is very rare for a cat to be infected with Lyme disease. However, cats are nevertheless capable of being infected with B. burgdorferi , following a bite from an infected tick. Cats who are infected with Lyme Disease may show symptoms including but not limited to lameness, fatigue, or loss of appetite. In two cases, the infected cats experienced cardiac irregularities similar to symptoms of Lyme in both dogs and humans. However, cats who are infected with Lyme disease are likely to be asymptomatic , and show no noticeable signs of the disease. Cats with Lyme are often treated with antibiotics, much like other animals. In some cases, additional treatment or therapy may be required. While Lyme disease can occur in horses, not every infection with B. burgdorferi is associated with symptoms. Especially, detection of specific antibodies against B. burgdorferi alone is not sufficient for a diagnosis of equine Lyme disease and unspecific testing for antibodies is not recommended.

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Tick-borne_encephalitis_virus/html

Tick-borne encephalitis virus

Absettarov virus Sofjin virus Tick-borne encephalitis virus ( TBEV ) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus Flavivirus .TBEV is a member of the genus Flavivirus . Other close relatives, members of the TBEV serocomplex, include Omsk hemorrhagic fever virus , Kyasanur Forest disease virus , Alkhurma virus , Louping ill virus and Langat virus . TBEV has three subtypes: The reference strain is the Sofjin strain. TBEV is a member of the genus Flavivirus . Other close relatives, members of the TBEV serocomplex, include Omsk hemorrhagic fever virus , Kyasanur Forest disease virus , Alkhurma virus , Louping ill virus and Langat virus . TBEV has three subtypes: The reference strain is the Sofjin strain. TBEV is a positive-sense single-stranded RNA virus , contained in a 40-60 nm spherical, enveloped capsid. The TBEV genome is approximately 11kb in size, which contains a 5' cap , a single open reading frame with 3' and 5' UTRs , and is without polyadenylation . Like other flaviviruses, the TBEV genome codes for ten viral proteins, three structural , and seven nonstructural . The structural proteins are C ( capsid ), PrM (premembrane), which is cleaved to produce the final membrane protein , (M), and envelope protein (E). The seven nonstructural proteins are: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The role of some nonstructural proteins is known, NS5 serves as RNA-dependent RNA polymerase , NS3 has protease (in complex with NS2B) and helicase activity. Structural and nonstructural proteins are not required for the genome to be infectious. All viral proteins are expressed as a single large polyprotein, with the order C, PrM, E, NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5. The envelope protein is involved in receptor-binding and neurovirulence, where increased glycosaminoglycan-binding affinity attenuates neuroinvasiveness. The conformation of the E protein during viral particle secretion is influenced by glycosylation as well. The immunogenicity of TBEV NS1 has been demonstrated, showcasing its ability to trigger oxidative stress and elicit the expression of immunoproteasome subunits. Additionally, it has been observed to stimulate the production of cytokines. The NS5 protein has interferon antagonist activity as it downregulates the expression of IFN receptor subunit. Non structural protein 5 (NS5) affects neuropathogenesis by attenuation of neurite outgrowth. Untranslated region 3 (UTR3) and UTR 5 affect genomic RNA cyclization and replication, and viral RNA transport in dendrites, which impacts neurogenesis and synaptic communication. Infection of the vector begins when a tick takes a blood meal from an infected host . This can occur at any part of the tick's life cycle but a horizontal transmission between infected nymphs and uninfected larvae co-feeding on the same host is thought to be key in maintaining the circulation of TBEV. TBEV in the blood of the host infects the tick through the midgut , from where it can pass to the salivary glands to be passed to the next host. In non-adult ticks, TBEV is transmitted transtadially by infecting cells that are not destroyed during molting , thus the tick remains infectious throughout its life. Infected adult ticks may be able to lay eggs that are infected, transmitting the virus transovarially . In humans, the infection begins in the skin (with the exception of food-borne cases, about 1% of infections) at the site of the bite of an infected tick, where Langerhans cells and macrophages in the skin are preferentially targeted. TBEV envelope (E) proteins recognize heparan sulfate (and likely other receptors) on the host cell surface and are endocytosed via the clathrin mediated pathway . Acidification of the late endosome triggers a conformational change in the E proteins, resulting in fusion, followed by uncoating, and release of the single-stranded RNA genome into the cytoplasm. The viral polyprotein is translated and inserts into the ER membrane, where it is processed on the cytosolic side by host peptidases and in the lumen by viral enzyme action. The viral proteins C, NS3, and NS5 are cleaved into the cytosol (though NS3 can complex with NS2B or NS4A to perform proteolytic or helicase activity), while the remaining nonstructural proteins alter the structure of the ER membrane. This altered membrane permits the assembly of replication complexes, where the viral genome is replicated by the viral RNA-dependent RNA polymerase , NS5. Newly replicated viral RNA genomes are then packaged by the C proteins while on the cytosolic side of the ER membrane, forming the immature nucleocapsid , and gain E and PrM proteins, arranged as a heterodimer, during budding into the lumen of the ER. The immature virion is spiky and geometric in comparison to the mature particle. The particle passes through the golgi apparatus and trans -golgi network, under increasingly acidic conditions, by which the virion matures with cleavage of the Pr segment from the M protein and formation fusion competent E protein homodimers. Though the cleaved Pr segment remains associated with protein complex until exit. The virus is released from the host cell upon fusion of the transport vesicle with the host cell membrane, the cleaved Pr now segments dissociate, resulting in a fully mature, infectious virus. However, partially mature and immature viruses are sometimes released as well; immature viruses are noninfectious as the E proteins are not fusion competent, partially mature viruses are still capable of infection. TBEV is a positive-sense single-stranded RNA virus , contained in a 40-60 nm spherical, enveloped capsid. The TBEV genome is approximately 11kb in size, which contains a 5' cap , a single open reading frame with 3' and 5' UTRs , and is without polyadenylation . Like other flaviviruses, the TBEV genome codes for ten viral proteins, three structural , and seven nonstructural . The structural proteins are C ( capsid ), PrM (premembrane), which is cleaved to produce the final membrane protein , (M), and envelope protein (E). The seven nonstructural proteins are: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The role of some nonstructural proteins is known, NS5 serves as RNA-dependent RNA polymerase , NS3 has protease (in complex with NS2B) and helicase activity. Structural and nonstructural proteins are not required for the genome to be infectious. All viral proteins are expressed as a single large polyprotein, with the order C, PrM, E, NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5. The envelope protein is involved in receptor-binding and neurovirulence, where increased glycosaminoglycan-binding affinity attenuates neuroinvasiveness. The conformation of the E protein during viral particle secretion is influenced by glycosylation as well. The immunogenicity of TBEV NS1 has been demonstrated, showcasing its ability to trigger oxidative stress and elicit the expression of immunoproteasome subunits. Additionally, it has been observed to stimulate the production of cytokines. The NS5 protein has interferon antagonist activity as it downregulates the expression of IFN receptor subunit. Non structural protein 5 (NS5) affects neuropathogenesis by attenuation of neurite outgrowth. Untranslated region 3 (UTR3) and UTR 5 affect genomic RNA cyclization and replication, and viral RNA transport in dendrites, which impacts neurogenesis and synaptic communication. Infection of the vector begins when a tick takes a blood meal from an infected host . This can occur at any part of the tick's life cycle but a horizontal transmission between infected nymphs and uninfected larvae co-feeding on the same host is thought to be key in maintaining the circulation of TBEV. TBEV in the blood of the host infects the tick through the midgut , from where it can pass to the salivary glands to be passed to the next host. In non-adult ticks, TBEV is transmitted transtadially by infecting cells that are not destroyed during molting , thus the tick remains infectious throughout its life. Infected adult ticks may be able to lay eggs that are infected, transmitting the virus transovarially . In humans, the infection begins in the skin (with the exception of food-borne cases, about 1% of infections) at the site of the bite of an infected tick, where Langerhans cells and macrophages in the skin are preferentially targeted. TBEV envelope (E) proteins recognize heparan sulfate (and likely other receptors) on the host cell surface and are endocytosed via the clathrin mediated pathway . Acidification of the late endosome triggers a conformational change in the E proteins, resulting in fusion, followed by uncoating, and release of the single-stranded RNA genome into the cytoplasm. The viral polyprotein is translated and inserts into the ER membrane, where it is processed on the cytosolic side by host peptidases and in the lumen by viral enzyme action. The viral proteins C, NS3, and NS5 are cleaved into the cytosol (though NS3 can complex with NS2B or NS4A to perform proteolytic or helicase activity), while the remaining nonstructural proteins alter the structure of the ER membrane. This altered membrane permits the assembly of replication complexes, where the viral genome is replicated by the viral RNA-dependent RNA polymerase , NS5. Newly replicated viral RNA genomes are then packaged by the C proteins while on the cytosolic side of the ER membrane, forming the immature nucleocapsid , and gain E and PrM proteins, arranged as a heterodimer, during budding into the lumen of the ER. The immature virion is spiky and geometric in comparison to the mature particle. The particle passes through the golgi apparatus and trans -golgi network, under increasingly acidic conditions, by which the virion matures with cleavage of the Pr segment from the M protein and formation fusion competent E protein homodimers. Though the cleaved Pr segment remains associated with protein complex until exit. The virus is released from the host cell upon fusion of the transport vesicle with the host cell membrane, the cleaved Pr now segments dissociate, resulting in a fully mature, infectious virus. However, partially mature and immature viruses are sometimes released as well; immature viruses are noninfectious as the E proteins are not fusion competent, partially mature viruses are still capable of infection. Infection of the vector begins when a tick takes a blood meal from an infected host . This can occur at any part of the tick's life cycle but a horizontal transmission between infected nymphs and uninfected larvae co-feeding on the same host is thought to be key in maintaining the circulation of TBEV. TBEV in the blood of the host infects the tick through the midgut , from where it can pass to the salivary glands to be passed to the next host. In non-adult ticks, TBEV is transmitted transtadially by infecting cells that are not destroyed during molting , thus the tick remains infectious throughout its life. Infected adult ticks may be able to lay eggs that are infected, transmitting the virus transovarially . In humans, the infection begins in the skin (with the exception of food-borne cases, about 1% of infections) at the site of the bite of an infected tick, where Langerhans cells and macrophages in the skin are preferentially targeted. TBEV envelope (E) proteins recognize heparan sulfate (and likely other receptors) on the host cell surface and are endocytosed via the clathrin mediated pathway . Acidification of the late endosome triggers a conformational change in the E proteins, resulting in fusion, followed by uncoating, and release of the single-stranded RNA genome into the cytoplasm. The viral polyprotein is translated and inserts into the ER membrane, where it is processed on the cytosolic side by host peptidases and in the lumen by viral enzyme action. The viral proteins C, NS3, and NS5 are cleaved into the cytosol (though NS3 can complex with NS2B or NS4A to perform proteolytic or helicase activity), while the remaining nonstructural proteins alter the structure of the ER membrane. This altered membrane permits the assembly of replication complexes, where the viral genome is replicated by the viral RNA-dependent RNA polymerase , NS5. Newly replicated viral RNA genomes are then packaged by the C proteins while on the cytosolic side of the ER membrane, forming the immature nucleocapsid , and gain E and PrM proteins, arranged as a heterodimer, during budding into the lumen of the ER. The immature virion is spiky and geometric in comparison to the mature particle. The particle passes through the golgi apparatus and trans -golgi network, under increasingly acidic conditions, by which the virion matures with cleavage of the Pr segment from the M protein and formation fusion competent E protein homodimers. Though the cleaved Pr segment remains associated with protein complex until exit. The virus is released from the host cell upon fusion of the transport vesicle with the host cell membrane, the cleaved Pr now segments dissociate, resulting in a fully mature, infectious virus. However, partially mature and immature viruses are sometimes released as well; immature viruses are noninfectious as the E proteins are not fusion competent, partially mature viruses are still capable of infection. With the exception of food-borne cases, infection begins in the skin at the site of the tick bite. Skin dendritic (or Langerhans) cells (DCs) are preferentially targeted. Initially, the virus replicates locally and immune response is triggered when viral components are recognized by cytosolic pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs). Recognition causes the release of cytokines including interferons (IFN) α, β , and γ and chemokines, attracting migratory immune cells to the site of the bite. The infection may be halted at this stage and cleared, before the onset of noticeable symptoms. Notably, tick saliva enhances infection by modulating host immune response, dampening apoptotic signals. If the infection continues, migratory DCs and macrophages become infected and travel to the local draining lymph node where activation of polymorphonuclear leukocytes , monocytes and the complement system are activated. The draining lymph node can also serve as a viral amplification site, from where TBEV gains systemic access. This viremic stage corresponds to the first symptomatic phase in the prototypical biphasic pattern of tick-borne encephalitis. TBEV has a strong preference for neuronal tissue, and is neuroinvasive. The initial viremic stage allows access to a number of the preferential tissues. However, the exact mechanism by which TBEV crosses into the central nervous system (CNS) is unclear. There are several proposed mechanism for TBEV breaching the blood-brain barrier (BBB): 1)The "Trojan Horse" mechanism, whereby TBEV gains access to the CNS while infecting an immune cell that passes through the BBB; 2) Disruption and increased permeability of the BBB by immune immune cytokines; 3) Via infection of the olfactory neurons; 4) Via retrograde transport along peripheral nerves to the CNS; 5) Infection of the cells that make up part of the BBB. CNS infection brings on the second phase in the classic biphasic infection pattern associated with the European subtype. CNS disease is immunopathological; release of inflammatory cytokines coupled with the action of cytotoxic CD8+ T cells and possibly NK cells results in inflammation and apoptosis of infected cells that is responsible for many of the CNS symptoms. TBEV specific IgM and IgG antibodies are produced in response to infection. IgM antibodies appear and peak first, as well as reaching higher levels, and typically dissipate in about 1.5 months post infection, though there exists considerable variation from patient to patient. IgG levels peak at about 6 weeks after the appearance of CNS symptoms, then decline slightly but do not dissipate, likely conferring life long immunity to the patient. TBEV specific IgM and IgG antibodies are produced in response to infection. IgM antibodies appear and peak first, as well as reaching higher levels, and typically dissipate in about 1.5 months post infection, though there exists considerable variation from patient to patient. IgG levels peak at about 6 weeks after the appearance of CNS symptoms, then decline slightly but do not dissipate, likely conferring life long immunity to the patient. The ancestor of the extant strains appears to have separated into several clades approximately 2750 years ago. The Siberian and Far Eastern subtypes diverged about 2250 years ago. A second analysis suggests an earlier date of evolution (3300 years ago) with a rapid increase in the number of strains starting around 300 years ago. Different strains of the virus have been transmitted at least three times into Japan between 260–430 years ago. The strains circulating in Latvia appear to have originated from both Russia and Western Europe while those in Estonia appear to have originated in Russia . The Lithuanian strains appear to be related to those from Western Europe. Phylogenetic analysis indicates that the European and Siberian TBEV sub-types are closely related while the Far-eastern sub-type is closer to the Louping Ill Virus. However, in antigenic relatedness, based on the E, NS3, and NS5 proteins, all three sub-types are highly similar, and Louping Ill virus is the closest relative outside the collective TBEV group. Though the first description of what may have been TBE appears in records in the 1700s in Scandinavia, identification of the TBEV virus occurred in the Soviet Union in the 1930s. The investigation began due to an outbreak of what was believed to be Japanese Encephalitis ("Summer encephalitis"), among Soviet troops stationed along the border with the Japanese empire (present day People's Republic of China ), near the Far Eastern city of Khabarovsk . The expedition was led by virologist Lev A. Zilber , who assembled a team of twenty young scientists in a number of related fields such as acarology , microbiology, neurology, and epidemiology. The expedition arrived in Khabarovsk on May 15, 1937, and divided into squads, Northern-led by Elizabeth N. Levkovich and working in the Khabarovski Krai - and Southern-led by Alexandra D. Sheboldaeva, working in the Primorski Krai . Inside the month of May, the expedition had identified ticks as the likely vector, collected I. persucatus ticks by exposure of bare skin by entomologist Alexander V. Gutsevich and virologist Mikhail P. Chumakov had isolated the virus from ticks feeding on intentionally infected mice. During the summer, five expeditions members became infected with TBEV, and while there were no fatalities, three of the five suffered damaging sequelae . The expedition returned in mid-August and in October 1937 Zilber and Sheboldova were arrested, falsely accused of spreading Japanese encephalitis. Expedition epidemiologist Tamara M. Safonov, was arrested the following January for protesting the charges against Zilber and Sheboldova. As a consequence of the arrests, one of the important initial works was published under the authorship of expedition acarologist, Vasily S. Mironov. Zilber was released in 1939 and managed to restore, along with Sheboldova, co-authorship on this initial work; however, Safanov and Sheboldova (who was not released) spent 18 years in labor camps .

Wiki

Chikungunya

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

Human papillomavirus infection

Human papillomavirus infection ( HPV infection ) is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions . These lesions, depending on the site affected, increase the risk of cancer of the cervix , vulva , vagina , penis , anus , mouth, tonsils, or throat . Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers . Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis . An HPV infection is caused by the human papillomavirus , a DNA virus from the papillomavirus family. Over 200 types have been described. An individual can become infected with more than one type of HPV, and the disease is only known to affect humans. More than 40 types may be spread through sexual contact and infect the anus and genitals . Risk factors for persistent infection by sexually transmitted types include early age of first sexual intercourse , multiple sexual partners, smoking, and poor immune function . These types are typically spread by sustained direct skin-to-skin contact, with vaginal and anal sex being the most common methods. HPV infection can also spread from a mother to baby during pregnancy . There is no evidence that HPV can spread via common items like toilet seats, but the types that cause warts may spread via surfaces such as floors. HPV is not killed by common hand sanitizers and disinfectants, increasing the possibility of the virus being transferred via non-living infectious agents called fomites . HPV vaccines can prevent the most common types of infection. To be most effective, inoculation should occur before the onset of sexual activity, and are therefore recommended between the ages of 9–13 years. Cervical cancer screening , such as the Papanicolaou test ("pap smear"), or examination of the cervix after applying acetic acid , can detect both early cancer and abnormal cells that may develop into cancer. Screening allows for early treatment which results in better outcomes. Screening has reduced both the number of cases and the number of deaths from cervical cancer. Genital warts can be removed by freezing . Nearly every sexually active individual is infected by HPV at some point in their lives. HPV is the most common sexually transmitted infection (STI) , globally. High-risk HPVs cause about 5% of all cancers worldwide and about 37,300 cases of cancer in the United States each year. Cervical cancer is among the most common cancers worldwide, causing an estimated 604,000 new cases and 342,000 deaths in 2020. About 90% of these new cases and deaths of cervical cancer occurred in low- and middle-income countries . Roughly 1% of sexually active adults have genital warts. Cases of skin warts have been described since the time of ancient Greece , but that they were caused by a virus was not determined until 1907. HPV is a group of more than 200 related viruses, which are designated by a number for each virus type. Some HPV types, such as HPV5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals. HPV types 6 and 11 can cause genital warts and laryngeal papillomatosis . Many HPV types are carcinogenic . About twelve HPV types (including types 16, 18, 31, and 45) are called "high-risk" types because persistent infection has been linked to cancer of the oropharynx , larynx , vulva , vagina , cervix , penis , and anus . These cancers all involve sexually transmitted infection of HPV to the stratified epithelial tissue . HPV type 16 is the strain most likely to cause cancer and is present in about 47% of all cervical cancers, and in many vaginal and vulvar cancers, penile cancers, anal cancers, and cancers of the head and neck. The table below lists common symptoms of HPV infection and the associated types of HPV. Available HPV vaccines protect against either two, four, or nine types of HPV. There are six prophylactic HPV vaccines licensed for use: the bivalent vaccines Cervarix , Cecolin , and Walrinvax ; the quadrivalent vaccines Cervavax and Gardasil ; and the nonavalent vaccine Gardasil 9 . All HPV vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. The quadrivalent vaccines also protect against HPV types 6 and 11. The nonavalent vaccine Gardasil 9 provides protection against those four types (6, 11, 16, and 18), along with five other high-risk HPV types responsible for 20% of cervical cancers (types 31, 33, 45, 52, and 58). Skin infection (" cutaneous " infection) with HPV is very widespread. Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin. While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907. Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is HPV type-specific, meaning an individual may become resistant to one HPV type while remaining susceptible to other types. [ citation needed ] Types of warts include: Common, flat, and plantar warts are much less likely to spread from person to person. HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide. Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection. [ citation needed ] The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases. However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic. [ citation needed ] The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV. [ citation needed ] In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis , in which warts form on the larynx or other areas of the respiratory tract. These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable. Cervical cancer is among the most common cancers worldwide, causing an estimated 604,000 new cases and 342,000 deaths in 2020. About 90% of these new cases and deaths of cervical cancer occurred in low- and middle-income countries , where screening tests and treatment of early cervical cell changes are not readily available. In the United States, about 37,300 cases of cancer due to HPV occur each year. In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer. Co-factors such as cigarette smoke can also enhance the risk of such HPV-related cancers. HPV is believed to cause cancer by integrating its genome into nuclear DNA . Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation . HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number. E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein ( E6-AP ). E6AP is an E3 Ubiquitin ligase , an enzyme whose purpose is to tag proteins with a post-translational modification called Ubiquitin. By binding both proteins, E6 induces E6AP to attach a chain of ubiquitin molecules to p53, thereby flagging p53 for proteosomal degradation. Normally, p53 acts to prevent cell growth and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F . In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, the degradation of p53, induced by E6, promotes unregulated cell division, cell growth and cell survival, all characteristics of cancer. It is important to note, that while the interaction between E6, E6AP and p53 was the first to be characterized, there are multiple other proteins in the host cell which interact with E6 and assist the induction of cancer. Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin . In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light . Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases. In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer : 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. One study found that 74% of squamous cell carcinomas and 78% of adenocarcinomas tested positive for HPV types 16 or 18. Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer. The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades . The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18 , respectively. These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis. In 2020, about 604,000 new cases and 342,000 deaths from cervical cancer occurred worldwide. Around 90% of these occurred in the developing world . Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the Clearance subsection in Virology ). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people having been infected with HPV for a long time, usually over a decade or more (persistent infection). Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways. Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants. The risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men. Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex. No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear. HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV. Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16) is associated with an increasing number of head and neck cancers . This association is independent of tobacco and alcohol use. The local percentage varies widely, from 70% in the United States to 4% in Brazil. Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers. In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases. The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988 to 4.5 per 100,000 in 2012, and, as of 2021, the rate has continued to increase. Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women. The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases. Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer. Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased. In addition, expression of HPV structural proteins by immunohistochemistry and in vitro studies suggest HPV presence in bronchial cancer and its precursor lesions. Another study detected HPV in the exhaled breath condensate (EBC), bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by nonsmall cell lung cancer, but in none of the controls. The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions. In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system . The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells , resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer , but the development is not well understood. The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14. Skin infection (" cutaneous " infection) with HPV is very widespread. Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin. While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907. Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is HPV type-specific, meaning an individual may become resistant to one HPV type while remaining susceptible to other types. [ citation needed ] Types of warts include: Common, flat, and plantar warts are much less likely to spread from person to person. HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide. Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection. [ citation needed ] The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases. However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic. [ citation needed ] The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV. [ citation needed ] In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis , in which warts form on the larynx or other areas of the respiratory tract. These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable. HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide. Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection. [ citation needed ] The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases. However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals. Such infections may cause genital warts, although they may also remain asymptomatic. [ citation needed ] The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV. [ citation needed ]In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis , in which warts form on the larynx or other areas of the respiratory tract. These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable. Cervical cancer is among the most common cancers worldwide, causing an estimated 604,000 new cases and 342,000 deaths in 2020. About 90% of these new cases and deaths of cervical cancer occurred in low- and middle-income countries , where screening tests and treatment of early cervical cell changes are not readily available. In the United States, about 37,300 cases of cancer due to HPV occur each year. In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer. Co-factors such as cigarette smoke can also enhance the risk of such HPV-related cancers. HPV is believed to cause cancer by integrating its genome into nuclear DNA . Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation . HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number. E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein ( E6-AP ). E6AP is an E3 Ubiquitin ligase , an enzyme whose purpose is to tag proteins with a post-translational modification called Ubiquitin. By binding both proteins, E6 induces E6AP to attach a chain of ubiquitin molecules to p53, thereby flagging p53 for proteosomal degradation. Normally, p53 acts to prevent cell growth and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F . In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, the degradation of p53, induced by E6, promotes unregulated cell division, cell growth and cell survival, all characteristics of cancer. It is important to note, that while the interaction between E6, E6AP and p53 was the first to be characterized, there are multiple other proteins in the host cell which interact with E6 and assist the induction of cancer. Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin . In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light . Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases. In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer : 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. One study found that 74% of squamous cell carcinomas and 78% of adenocarcinomas tested positive for HPV types 16 or 18. Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer. The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades . The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18 , respectively. These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis. In 2020, about 604,000 new cases and 342,000 deaths from cervical cancer occurred worldwide. Around 90% of these occurred in the developing world . Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the Clearance subsection in Virology ). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people having been infected with HPV for a long time, usually over a decade or more (persistent infection). Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways. Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants. The risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men. Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex. No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear. HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV. Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16) is associated with an increasing number of head and neck cancers . This association is independent of tobacco and alcohol use. The local percentage varies widely, from 70% in the United States to 4% in Brazil. Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers. In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases. The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988 to 4.5 per 100,000 in 2012, and, as of 2021, the rate has continued to increase. Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women. The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases. Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer. Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased. In addition, expression of HPV structural proteins by immunohistochemistry and in vitro studies suggest HPV presence in bronchial cancer and its precursor lesions. Another study detected HPV in the exhaled breath condensate (EBC), bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by nonsmall cell lung cancer, but in none of the controls. The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions. In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system . The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells , resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer , but the development is not well understood. The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14. Cervical cancer is among the most common cancers worldwide, causing an estimated 604,000 new cases and 342,000 deaths in 2020. About 90% of these new cases and deaths of cervical cancer occurred in low- and middle-income countries , where screening tests and treatment of early cervical cell changes are not readily available. In the United States, about 37,300 cases of cancer due to HPV occur each year. In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer. Co-factors such as cigarette smoke can also enhance the risk of such HPV-related cancers. HPV is believed to cause cancer by integrating its genome into nuclear DNA . Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation . HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number. E6 produces a protein (also called E6) that simultaneously binds to two host cell proteins called p53 and E6-Associated Protein ( E6-AP ). E6AP is an E3 Ubiquitin ligase , an enzyme whose purpose is to tag proteins with a post-translational modification called Ubiquitin. By binding both proteins, E6 induces E6AP to attach a chain of ubiquitin molecules to p53, thereby flagging p53 for proteosomal degradation. Normally, p53 acts to prevent cell growth and promotes cell death in the presence of DNA damage. p53 also upregulates the p21 protein, which blocks the formation of the cyclin D/Cdk4 complex, thereby preventing the phosphorylation of retinoblastoma protein (RB), and in turn, halting cell cycle progression by preventing the activation of E2F . In short, p53 is a tumor-suppressor protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, the degradation of p53, induced by E6, promotes unregulated cell division, cell growth and cell survival, all characteristics of cancer. It is important to note, that while the interaction between E6, E6AP and p53 was the first to be characterized, there are multiple other proteins in the host cell which interact with E6 and assist the induction of cancer. Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin . In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light . Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases. In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer : 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. One study found that 74% of squamous cell carcinomas and 78% of adenocarcinomas tested positive for HPV types 16 or 18. Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer. The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades . The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18 , respectively. These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis. In 2020, about 604,000 new cases and 342,000 deaths from cervical cancer occurred worldwide. Around 90% of these occurred in the developing world . Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the Clearance subsection in Virology ). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people having been infected with HPV for a long time, usually over a decade or more (persistent infection). Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways. Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants. The risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men. Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex. No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear. HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV. Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16) is associated with an increasing number of head and neck cancers . This association is independent of tobacco and alcohol use. The local percentage varies widely, from 70% in the United States to 4% in Brazil. Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers. In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases. The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988 to 4.5 per 100,000 in 2012, and, as of 2021, the rate has continued to increase. Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women. The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases. Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer. Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased. In addition, expression of HPV structural proteins by immunohistochemistry and in vitro studies suggest HPV presence in bronchial cancer and its precursor lesions. Another study detected HPV in the exhaled breath condensate (EBC), bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by nonsmall cell lung cancer, but in none of the controls. The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions. In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system . The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells , resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer , but the development is not well understood. The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14. Sexually transmitted HPV is divided into two categories: low-risk and high-risk. Low-risk HPVs cause warts on or around the genitals. Type 6 and 11 cause 90% of all genital warts and recurrent respiratory papillomatosis that causes benign tumors in the air passages. High-risk HPVs cause cancer and consist of about twelve identified types. Types 16 and 18 are responsible for causing most of HPV-caused cancers. These high-risk HPVs cause 5% of the cancers in the world. In the United States, high-risk HPVs cause 3% of all cancer cases in women and 2% in men. Risk factors for persistent genital HPV infections, which increases the risk for developing cancer, include early age of first sexual intercourse, multiple partners, smoking, and immunosuppression. Genital HPV is spread by sustained direct skin-to-skin contact, with vaginal, anal, and oral sex being the most common methods. Occasionally, it can spread from manual sex or from a mother to her baby during pregnancy . HPV is difficult to remove via standard hospital disinfection techniques, and may be transmitted in a healthcare setting on re-usable gynecological equipment, such as vaginal ultrasound transducers. The period of communicability is still unknown, but probably at least as long as visible HPV lesions persist. HPV may still be transmitted even after lesions are treated and no longer visible or present. Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%. [ citation needed ] Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner. Of the 120 known human papilloma viruses, 51 species and three subtypes infect the genital mucosa. Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89). Condoms do not completely protect from the virus because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person's skin. Studies have shown HPV transmission between hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand. Hands were not the main source of transmission in these 25 couples, but they were significant. [ citation needed ] Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per two years) as their genitals (48%). Winer reports 14% of fingertip samples from sexually active women were positive. Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72). Sharing of possibly contaminated objects, for example, razors, may transmit HPV. Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission but unlikely to be a significant source. Though it has traditionally been assumed that HPV is not transmissible via blood – as it is thought to only infect cutaneous and mucosal tissues – recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients. In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16. This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion . However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples. However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations such as the American Red Cross and other Red Cross societies do not presently appear to disallow HPV-positive individuals from donating blood. Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, is subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart). There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata. HPV infection is limited to the basal cells of stratified epithelium , the only tissue in which they replicate. The virus cannot bind to live tissue; instead, it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane . The infectious process is slow, taking 12–24 hours for initiation of transcription. It is believed that involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces. HPV lesions are thought to arise from the proliferation of infected basal keratinocytes . Infection typically occurs when basal cells in the host are exposed to the infectious virus through a disturbed epithelial barrier as would occur during sexual intercourse or after minor skin abrasions. HPV infections have not been shown to be cytolytic ; rather, viral particles are released as a result of degeneration of desquamating cells. HPV can survive for many months and at low temperatures without a host; therefore, an individual with plantar warts can spread the virus by walking barefoot. HPV is a small double-stranded circular DNA virus with a genome of approximately 8000 base pairs. The HPV life cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby the virion associates with putative receptors such as alpha integrins , laminins , and annexin A2 leading to entry of the virions into basal epithelial cells through clathrin - mediated endocytosis and/or caveolin -mediated endocytosis depending on the type of HPV. At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number of 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium. [ citation needed ] The phylogeny of the various strains of HPV generally reflects the migration patterns of Homo sapiens and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population. Researchers initially identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE). More recent analyses based on thousands of HPV16 genomes show that indeed two major clades exist, that are further subdivided into four lineages (designated A-D) and even further subdivided into 16 sublineages (A1–4, B1–4, C1–4 and D1–4). The A1-A3 sublineages constitute the European variant, A4 the Asian variant, B1-B4 the African type I variant, C1–C4 the African type II variant, D1 the North American variant, D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have different oncogenic capacity, where overall, the non-European lineages are considered to increase the risk for cancer. Although HPV16 is a DNA virus, there are signs of recombination among the different lineages. Based on an analysis of more than 3600 genomes, between 0.3 and 1.2% of them could be recombinant. Thus, ideally, genotyping (for cancer-risk assessment) of HPV16 should not be based only on certain genes, but on all genes from the entire genome. A bioinformatics tool named HPV16-Genotyper performs i) HPV16 lineage genotyping, ii) it detects potential recombination events, iii) it identifies, within the submitted sequences, mutations/SNPs that have been reported (in literature) to increase the risk for cancer. The two primary oncoproteins of high risk HPV types are E6 and E7. The "E" designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression). The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), two late (L1 and L2) ORFs, and a non-coding long control region (LCR). After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs . One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein. However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into host genome by disruption of E2 ORF, preventing E2 repression on E6 and E7. Thus, viral genome integration into host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop. Sometimes papillomavirus genomes are found integrated into the host genome, and this is especially noticeable with oncogenic HPVs. The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines in vitro . It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions, and increases their specific infectivity. Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues. A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers. Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection. Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e. the types found in cancers). [ citation needed ] Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance." Sexually transmitted HPV is divided into two categories: low-risk and high-risk. Low-risk HPVs cause warts on or around the genitals. Type 6 and 11 cause 90% of all genital warts and recurrent respiratory papillomatosis that causes benign tumors in the air passages. High-risk HPVs cause cancer and consist of about twelve identified types. Types 16 and 18 are responsible for causing most of HPV-caused cancers. These high-risk HPVs cause 5% of the cancers in the world. In the United States, high-risk HPVs cause 3% of all cancer cases in women and 2% in men. Risk factors for persistent genital HPV infections, which increases the risk for developing cancer, include early age of first sexual intercourse, multiple partners, smoking, and immunosuppression. Genital HPV is spread by sustained direct skin-to-skin contact, with vaginal, anal, and oral sex being the most common methods. Occasionally, it can spread from manual sex or from a mother to her baby during pregnancy . HPV is difficult to remove via standard hospital disinfection techniques, and may be transmitted in a healthcare setting on re-usable gynecological equipment, such as vaginal ultrasound transducers. The period of communicability is still unknown, but probably at least as long as visible HPV lesions persist. HPV may still be transmitted even after lesions are treated and no longer visible or present. Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%. [ citation needed ] Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner. Of the 120 known human papilloma viruses, 51 species and three subtypes infect the genital mucosa. Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89). Condoms do not completely protect from the virus because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person's skin. Studies have shown HPV transmission between hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand. Hands were not the main source of transmission in these 25 couples, but they were significant. [ citation needed ] Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per two years) as their genitals (48%). Winer reports 14% of fingertip samples from sexually active women were positive. Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72). Sharing of possibly contaminated objects, for example, razors, may transmit HPV. Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission but unlikely to be a significant source. Though it has traditionally been assumed that HPV is not transmissible via blood – as it is thought to only infect cutaneous and mucosal tissues – recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients. In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16. This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion . However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples. However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations such as the American Red Cross and other Red Cross societies do not presently appear to disallow HPV-positive individuals from donating blood. Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, is subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart). There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata. Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%. [ citation needed ]Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner. Of the 120 known human papilloma viruses, 51 species and three subtypes infect the genital mucosa. Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89). Condoms do not completely protect from the virus because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person's skin. Studies have shown HPV transmission between hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand. Hands were not the main source of transmission in these 25 couples, but they were significant. [ citation needed ] Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per two years) as their genitals (48%). Winer reports 14% of fingertip samples from sexually active women were positive. Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72). Sharing of possibly contaminated objects, for example, razors, may transmit HPV. Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission but unlikely to be a significant source. Though it has traditionally been assumed that HPV is not transmissible via blood – as it is thought to only infect cutaneous and mucosal tissues – recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients. In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16. This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion . However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples. However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations such as the American Red Cross and other Red Cross societies do not presently appear to disallow HPV-positive individuals from donating blood. Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, is subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart). There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata. HPV infection is limited to the basal cells of stratified epithelium , the only tissue in which they replicate. The virus cannot bind to live tissue; instead, it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane . The infectious process is slow, taking 12–24 hours for initiation of transcription. It is believed that involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces. HPV lesions are thought to arise from the proliferation of infected basal keratinocytes . Infection typically occurs when basal cells in the host are exposed to the infectious virus through a disturbed epithelial barrier as would occur during sexual intercourse or after minor skin abrasions. HPV infections have not been shown to be cytolytic ; rather, viral particles are released as a result of degeneration of desquamating cells. HPV can survive for many months and at low temperatures without a host; therefore, an individual with plantar warts can spread the virus by walking barefoot. HPV is a small double-stranded circular DNA virus with a genome of approximately 8000 base pairs. The HPV life cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby the virion associates with putative receptors such as alpha integrins , laminins , and annexin A2 leading to entry of the virions into basal epithelial cells through clathrin - mediated endocytosis and/or caveolin -mediated endocytosis depending on the type of HPV. At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number of 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium. [ citation needed ] The phylogeny of the various strains of HPV generally reflects the migration patterns of Homo sapiens and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population. Researchers initially identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE). More recent analyses based on thousands of HPV16 genomes show that indeed two major clades exist, that are further subdivided into four lineages (designated A-D) and even further subdivided into 16 sublineages (A1–4, B1–4, C1–4 and D1–4). The A1-A3 sublineages constitute the European variant, A4 the Asian variant, B1-B4 the African type I variant, C1–C4 the African type II variant, D1 the North American variant, D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have different oncogenic capacity, where overall, the non-European lineages are considered to increase the risk for cancer. Although HPV16 is a DNA virus, there are signs of recombination among the different lineages. Based on an analysis of more than 3600 genomes, between 0.3 and 1.2% of them could be recombinant. Thus, ideally, genotyping (for cancer-risk assessment) of HPV16 should not be based only on certain genes, but on all genes from the entire genome. A bioinformatics tool named HPV16-Genotyper performs i) HPV16 lineage genotyping, ii) it detects potential recombination events, iii) it identifies, within the submitted sequences, mutations/SNPs that have been reported (in literature) to increase the risk for cancer. The two primary oncoproteins of high risk HPV types are E6 and E7. The "E" designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression). The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), two late (L1 and L2) ORFs, and a non-coding long control region (LCR). After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs . One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein. However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into host genome by disruption of E2 ORF, preventing E2 repression on E6 and E7. Thus, viral genome integration into host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop. Sometimes papillomavirus genomes are found integrated into the host genome, and this is especially noticeable with oncogenic HPVs. The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines in vitro . It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions, and increases their specific infectivity. Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues. A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers. Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection. Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e. the types found in cancers). [ citation needed ] Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance." The phylogeny of the various strains of HPV generally reflects the migration patterns of Homo sapiens and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population. Researchers initially identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE). More recent analyses based on thousands of HPV16 genomes show that indeed two major clades exist, that are further subdivided into four lineages (designated A-D) and even further subdivided into 16 sublineages (A1–4, B1–4, C1–4 and D1–4). The A1-A3 sublineages constitute the European variant, A4 the Asian variant, B1-B4 the African type I variant, C1–C4 the African type II variant, D1 the North American variant, D2 the Asian American type I variant, D3 the Asian American type II variant. The various lineages and sublineages have different oncogenic capacity, where overall, the non-European lineages are considered to increase the risk for cancer. Although HPV16 is a DNA virus, there are signs of recombination among the different lineages. Based on an analysis of more than 3600 genomes, between 0.3 and 1.2% of them could be recombinant. Thus, ideally, genotyping (for cancer-risk assessment) of HPV16 should not be based only on certain genes, but on all genes from the entire genome. A bioinformatics tool named HPV16-Genotyper performs i) HPV16 lineage genotyping, ii) it detects potential recombination events, iii) it identifies, within the submitted sequences, mutations/SNPs that have been reported (in literature) to increase the risk for cancer. The two primary oncoproteins of high risk HPV types are E6 and E7. The "E" designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression). The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), two late (L1 and L2) ORFs, and a non-coding long control region (LCR). After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs . One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein. However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into host genome by disruption of E2 ORF, preventing E2 repression on E6 and E7. Thus, viral genome integration into host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop. Sometimes papillomavirus genomes are found integrated into the host genome, and this is especially noticeable with oncogenic HPVs. The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines in vitro . It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions, and increases their specific infectivity. Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues. A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers. Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection. Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e. the types found in cancers). [ citation needed ] Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance." Over 200 types of HPV have been identified, and they are designated by numbers. They may be divided into "low-risk" and "high-risk" types. Low-risk types cause warts and high-risk types can cause lesions or cancer. Guidelines from the American Cancer Society recommend different screening strategies for cervical cancer based on a woman's age, screening history, risk factors and choice of tests. Because of the link between HPV and cervical cancer, the ACS currently recommends early detection of cervical cancer in average-risk asymptomatic adults primarily with cervical cytology by Pap smear, regardless of HPV vaccination status. Women aged 30–65 should preferably be tested every 5 years with both the HPV test and the Pap test. In other age groups, a Pap test alone can suffice unless they have been diagnosed with atypical squamous cells of undetermined significance (ASC-US). Co-testing with a Pap test and HPV test is recommended because it decreases the rate of false-negatives. According to the National Cancer Institute, "The most common test detects DNA from several high-risk HPV types, but it cannot identify the types that are present. Another test is specific for DNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. A third test can detect DNA from several high-risk HPV types and can indicate whether HPV-16 or HPV-18 is present. A fourth test detects RNA from the most common high-risk HPV types. These tests can detect HPV infections before cell abnormalities are evident. [ citation needed ] "Theoretically, the HPV DNA and RNA tests could be used to identify HPV infections in cells taken from any part of the body. However, the tests are approved by the FDA for only two indications: for follow-up testing of women who seem to have abnormal Pap test results and for cervical cancer screening in combination with a Pap test among women over age 30." Guidelines for oropharyngeal cancer screening by the Preventive Services Task Force and American Dental Association in the U.S. suggest conventional visual examination, but because some parts of the oropharynx are hard to see, this cancer is often only detected in later stages. The diagnosis of oropharyngeal cancer occurs by biopsy of exfoliated cells or tissues. The National Comprehensive Cancer Network and College of American Pathologists recommend testing for HPV in oropharyngeal cancer. However, while testing is recommended, there is no specific type of test used to detect HPV from oral tumors that is currently recommended by the FDA in the United States. Because HPV type 16 is the most common type found in oropharyngeal cancer, p16 immunohistochemistry is one test option used to determine if HPV is present, which can help determine course of treatment since tumors that are negative for p16 have better outcomes. Another option that has emerged as a reliable option is HPV DNA in situ hybridization (ISH) which allows for visualization of the HPV. There is not a wide range of tests available even though HPV is common; most studies of HPV used tools and custom analysis not available to the general public. [ needs update ] Clinicians often depend on the vaccine among young people and high clearance rates (see Clearance subsection in Virology ) to create a low risk of disease and mortality, and treat the cancers when they appear. Others believe that reducing HPV infection in more men and women, even when it has no symptoms, is important (herd immunity) to prevent more cancers rather than just treating them. [ needs update ] Where tests are used, negative test results show safety from transmission, and positive test results show where shielding (condoms, gloves) is needed to prevent transmission until the infection clears. Studies have tested for and found HPV in men, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis. The Qiagen/Digene kit mentioned in the previous section was used successfully off label to test the penis, scrotum and anus of men in long-term relationships with women who were positive for high-risk HPV. 60% of them were found to carry the virus, primarily on the penis. [ needs update ] Other studies used cytobrushes and custom analysis. [ needs update ] In one study researchers sampled subjects' urethra, scrotum and penis. [ needs update ] Samples taken from the urethra added less than 1% to the HPV rate. Studies like this led Giuliano to recommend sampling the glans, shaft and crease between them, along with the scrotum, since sampling the urethra or anus added very little to the diagnosis. Dunne recommends the glans, shaft, their crease, and the foreskin. In one study the subjects were asked not to wash their genitals for 12 hours before sampling, including the urethra as well as the scrotum and the penis. Other studies are silent on washing – a particular gap in studies of the hands. [ citation needed ] One small study used wet cytobrushes, rather than wet the skin. It found a higher proportion of men to be HPV-positive when the skin was rubbed with a 600 grit emery paper before being swabbed with the brush, rather than swabbed with no preparation. It's unclear whether the emery paper collected the virions or simply loosened them for the swab to collect. [ citation needed ] Studies have found self-collection (with emery paper and Dacron swabs) as effective as collection done by a clinician, and sometimes more so, since patients were more willing than a clinician to scrape vigorously. [ needs update ] Women had similar success in self-sampling using tampons, swabs, cytobrushes and lavage. [ needs update ] Several studies used cytobrushes to sample fingertips and under fingernails, without wetting the area or the brush. [ needs update ] Other studies analyzed urine, semen, and blood and found varying amounts of HPV, but there is not a publicly available test for those yet. Although it is possible to test for HPV DNA in other kinds of infections, there are no FDA-approved tests for general screening in the United States or tests approved by the Canadian government, since the testing is inconclusive and considered medically unnecessary. Genital warts are the only visible sign of low-risk genital HPV and can be identified with a visual check. These visible growths, however, are the result of non-carcinogenic HPV types. Five percent acetic acid (vinegar) is used to identify both warts and squamous intraepithelial neoplasia (SIL) lesions with limited success [ citation needed ] by causing abnormal tissue to appear white, but most doctors have found this technique helpful only in moist areas, such as the female genital tract. [ citation needed ] At this time, HPV tests for males are used only in research. [ citation needed ] Research into testing for HPV by antibody presence has been done. The approach is looking for an immune response in blood, which would contain antibodies for HPV if the patient is HPV positive. The reliability of such tests has not been proven, as there has not been a FDA approved product as of August 2018; testing by blood would be a less invasive test for screening purposes.Guidelines from the American Cancer Society recommend different screening strategies for cervical cancer based on a woman's age, screening history, risk factors and choice of tests. Because of the link between HPV and cervical cancer, the ACS currently recommends early detection of cervical cancer in average-risk asymptomatic adults primarily with cervical cytology by Pap smear, regardless of HPV vaccination status. Women aged 30–65 should preferably be tested every 5 years with both the HPV test and the Pap test. In other age groups, a Pap test alone can suffice unless they have been diagnosed with atypical squamous cells of undetermined significance (ASC-US). Co-testing with a Pap test and HPV test is recommended because it decreases the rate of false-negatives. According to the National Cancer Institute, "The most common test detects DNA from several high-risk HPV types, but it cannot identify the types that are present. Another test is specific for DNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. A third test can detect DNA from several high-risk HPV types and can indicate whether HPV-16 or HPV-18 is present. A fourth test detects RNA from the most common high-risk HPV types. These tests can detect HPV infections before cell abnormalities are evident. [ citation needed ] "Theoretically, the HPV DNA and RNA tests could be used to identify HPV infections in cells taken from any part of the body. However, the tests are approved by the FDA for only two indications: for follow-up testing of women who seem to have abnormal Pap test results and for cervical cancer screening in combination with a Pap test among women over age 30." Guidelines for oropharyngeal cancer screening by the Preventive Services Task Force and American Dental Association in the U.S. suggest conventional visual examination, but because some parts of the oropharynx are hard to see, this cancer is often only detected in later stages. The diagnosis of oropharyngeal cancer occurs by biopsy of exfoliated cells or tissues. The National Comprehensive Cancer Network and College of American Pathologists recommend testing for HPV in oropharyngeal cancer. However, while testing is recommended, there is no specific type of test used to detect HPV from oral tumors that is currently recommended by the FDA in the United States. Because HPV type 16 is the most common type found in oropharyngeal cancer, p16 immunohistochemistry is one test option used to determine if HPV is present, which can help determine course of treatment since tumors that are negative for p16 have better outcomes. Another option that has emerged as a reliable option is HPV DNA in situ hybridization (ISH) which allows for visualization of the HPV. There is not a wide range of tests available even though HPV is common; most studies of HPV used tools and custom analysis not available to the general public. [ needs update ] Clinicians often depend on the vaccine among young people and high clearance rates (see Clearance subsection in Virology ) to create a low risk of disease and mortality, and treat the cancers when they appear. Others believe that reducing HPV infection in more men and women, even when it has no symptoms, is important (herd immunity) to prevent more cancers rather than just treating them. [ needs update ] Where tests are used, negative test results show safety from transmission, and positive test results show where shielding (condoms, gloves) is needed to prevent transmission until the infection clears. Studies have tested for and found HPV in men, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis. The Qiagen/Digene kit mentioned in the previous section was used successfully off label to test the penis, scrotum and anus of men in long-term relationships with women who were positive for high-risk HPV. 60% of them were found to carry the virus, primarily on the penis. [ needs update ] Other studies used cytobrushes and custom analysis. [ needs update ] In one study researchers sampled subjects' urethra, scrotum and penis. [ needs update ] Samples taken from the urethra added less than 1% to the HPV rate. Studies like this led Giuliano to recommend sampling the glans, shaft and crease between them, along with the scrotum, since sampling the urethra or anus added very little to the diagnosis. Dunne recommends the glans, shaft, their crease, and the foreskin. In one study the subjects were asked not to wash their genitals for 12 hours before sampling, including the urethra as well as the scrotum and the penis. Other studies are silent on washing – a particular gap in studies of the hands. [ citation needed ] One small study used wet cytobrushes, rather than wet the skin. It found a higher proportion of men to be HPV-positive when the skin was rubbed with a 600 grit emery paper before being swabbed with the brush, rather than swabbed with no preparation. It's unclear whether the emery paper collected the virions or simply loosened them for the swab to collect. [ citation needed ] Studies have found self-collection (with emery paper and Dacron swabs) as effective as collection done by a clinician, and sometimes more so, since patients were more willing than a clinician to scrape vigorously. [ needs update ] Women had similar success in self-sampling using tampons, swabs, cytobrushes and lavage. [ needs update ] Several studies used cytobrushes to sample fingertips and under fingernails, without wetting the area or the brush. [ needs update ] Other studies analyzed urine, semen, and blood and found varying amounts of HPV, but there is not a publicly available test for those yet.Although it is possible to test for HPV DNA in other kinds of infections, there are no FDA-approved tests for general screening in the United States or tests approved by the Canadian government, since the testing is inconclusive and considered medically unnecessary. Genital warts are the only visible sign of low-risk genital HPV and can be identified with a visual check. These visible growths, however, are the result of non-carcinogenic HPV types. Five percent acetic acid (vinegar) is used to identify both warts and squamous intraepithelial neoplasia (SIL) lesions with limited success [ citation needed ] by causing abnormal tissue to appear white, but most doctors have found this technique helpful only in moist areas, such as the female genital tract. [ citation needed ] At this time, HPV tests for males are used only in research. [ citation needed ] Research into testing for HPV by antibody presence has been done. The approach is looking for an immune response in blood, which would contain antibodies for HPV if the patient is HPV positive. The reliability of such tests has not been proven, as there has not been a FDA approved product as of August 2018; testing by blood would be a less invasive test for screening purposes.The HPV vaccines can prevent the most common types of infection. To be effective they must be used before an infection occurs and are therefore recommended between the ages of nine and thirteen. Cervical cancer screening , such as with the Papanicolaou test (pap) or looking at the cervix after using acetic acid , can detect early cancer or abnormal cells that may develop into cancer. This allows for early treatment which results in better outcomes. Screening has reduced both the number and deaths from cervical cancer in the developed world. Warts can be removed by freezing . Three vaccines are available to prevent infection by some HPV types: Gardasil , Gardasil 9 and Cervarix ; all three protect against initial infection with HPV types 16 and 18, which cause most of the HPV-associated cancer cases. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. Gardasil is a recombinant quadrivalent vaccine, whereas Cervarix is bivalent, and is prepared from virus-like particles (VLP) of the L1 capsid protein . Gardasil 9 is nonavalent, having the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers. It can protect for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the latter five cause up to 20% of cervical cancers which were not previously covered. The vaccines provide little benefit to women already infected with HPV types 16 and 18. For this reason, the vaccine is recommended primarily for those women not yet having been exposed to HPV during sex. The World Health Organization position paper on HPV vaccination clearly outlines appropriate, cost-effective strategies for using HPV vaccine in public sector programs. There is high-certainty evidence that HPV vaccines protect against precancerous cervical lesions in young women, particularly those vaccinated aged 15 to 26. HPV vaccines do not increase the risk of serious adverse events. Longer follow-up is needed to monitor the impact of HPV vaccines on cervical cancer. The CDC recommends the vaccines be delivered in two shots at an interval of least 6 months for those aged 11–12, and three doses for those 13 and older. In most countries, they are funded only for female use, but are approved for male use in many countries, and funded for teenage boys in Australia. The vaccine does not have any therapeutic effect on existing HPV infections or cervical lesions. In 2010, 49% of teenage girls in the US got the HPV vaccine. [ citation needed ] Following studies suggesting that the vaccine is more effective in younger girls than in older teenagers, the United Kingdom, Switzerland, Mexico, the Netherlands and Quebec began offering the vaccine in a two-dose schedule for girls aged under 15 in 2014. [ citation needed ] Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. It remains a recommendation that women continue cervical screening, such as Pap smear testing, even after receiving the vaccine, since it does not prevent all types of cervical cancer. Both men and women are carriers of HPV. The Gardasil vaccine also protects men against anal cancers and warts and genital warts. Duration of both vaccines' efficacy has been observed since they were first developed, and is expected to be longlasting. In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, Gardasil 9, to protect against infection with the four strains of HPV covered by the first generation of Gardasil as well as five other strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58). The Centers for Disease Control and Prevention says that male " condom use may reduce the risk for genital human papillomavirus (HPV) infection" but provides a lesser degree of protection compared with other sexual transmitted infections "because HPV also may be transmitted by exposure to areas (e.g., infected skin or mucosal surfaces) that are not covered or protected by the condom." The virus is unusually hardy, and is immune to most common disinfectants. It is the first virus ever shown to be resistant to inactivation by glutaraldehyde , which is among the most common strong disinfectants used in hospitals. Diluted sodium hypochlorite bleach is effective, but cannot be used on some types of re-usable equipment, such as ultrasound transducers. As a result of these difficulties, there is developing concern about the possibility of transmitting the virus on healthcare equipment, particularly reusable gynecological equipment that cannot be autoclaved . For such equipment, some health authorities encourage use of UV disinfection or a non-hypochlorite "oxidizing‐based high‐level disinfectant [bleach] with label claims for non‐enveloped viruses", such as a strong hydrogen peroxide solution or chlorine dioxide wipes. Such disinfection methods are expected to be relatively effective against HPV. [ citation needed ]Three vaccines are available to prevent infection by some HPV types: Gardasil , Gardasil 9 and Cervarix ; all three protect against initial infection with HPV types 16 and 18, which cause most of the HPV-associated cancer cases. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. Gardasil is a recombinant quadrivalent vaccine, whereas Cervarix is bivalent, and is prepared from virus-like particles (VLP) of the L1 capsid protein . Gardasil 9 is nonavalent, having the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers. It can protect for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the latter five cause up to 20% of cervical cancers which were not previously covered. The vaccines provide little benefit to women already infected with HPV types 16 and 18. For this reason, the vaccine is recommended primarily for those women not yet having been exposed to HPV during sex. The World Health Organization position paper on HPV vaccination clearly outlines appropriate, cost-effective strategies for using HPV vaccine in public sector programs. There is high-certainty evidence that HPV vaccines protect against precancerous cervical lesions in young women, particularly those vaccinated aged 15 to 26. HPV vaccines do not increase the risk of serious adverse events. Longer follow-up is needed to monitor the impact of HPV vaccines on cervical cancer. The CDC recommends the vaccines be delivered in two shots at an interval of least 6 months for those aged 11–12, and three doses for those 13 and older. In most countries, they are funded only for female use, but are approved for male use in many countries, and funded for teenage boys in Australia. The vaccine does not have any therapeutic effect on existing HPV infections or cervical lesions. In 2010, 49% of teenage girls in the US got the HPV vaccine. [ citation needed ] Following studies suggesting that the vaccine is more effective in younger girls than in older teenagers, the United Kingdom, Switzerland, Mexico, the Netherlands and Quebec began offering the vaccine in a two-dose schedule for girls aged under 15 in 2014. [ citation needed ] Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. It remains a recommendation that women continue cervical screening, such as Pap smear testing, even after receiving the vaccine, since it does not prevent all types of cervical cancer. Both men and women are carriers of HPV. The Gardasil vaccine also protects men against anal cancers and warts and genital warts. Duration of both vaccines' efficacy has been observed since they were first developed, and is expected to be longlasting. In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, Gardasil 9, to protect against infection with the four strains of HPV covered by the first generation of Gardasil as well as five other strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58). The Centers for Disease Control and Prevention says that male " condom use may reduce the risk for genital human papillomavirus (HPV) infection" but provides a lesser degree of protection compared with other sexual transmitted infections "because HPV also may be transmitted by exposure to areas (e.g., infected skin or mucosal surfaces) that are not covered or protected by the condom." The virus is unusually hardy, and is immune to most common disinfectants. It is the first virus ever shown to be resistant to inactivation by glutaraldehyde , which is among the most common strong disinfectants used in hospitals. Diluted sodium hypochlorite bleach is effective, but cannot be used on some types of re-usable equipment, such as ultrasound transducers. As a result of these difficulties, there is developing concern about the possibility of transmitting the virus on healthcare equipment, particularly reusable gynecological equipment that cannot be autoclaved . For such equipment, some health authorities encourage use of UV disinfection or a non-hypochlorite "oxidizing‐based high‐level disinfectant [bleach] with label claims for non‐enveloped viruses", such as a strong hydrogen peroxide solution or chlorine dioxide wipes. Such disinfection methods are expected to be relatively effective against HPV. [ citation needed ]There is currently no specific treatment for HPV infection. However, the viral infection is usually cleared to undetectable levels by the immune system. According to the Centers for Disease Control and Prevention , the body's immune system clears HPV naturally within two years for 90% of cases (see Clearance subsection in Virology for more detail). However, experts do not agree on whether the virus is eliminated or reduced to undetectable levels, and it is difficult to know when it is contagious. [ needs update ] Follow up care is usually recommended and practiced by many health clinics. Follow-up is sometimes not successful because a portion of those treated do not return to be evaluated. In addition to the normal methods of phone calls and mail, text messaging and email can improve the number of people who return for care. As of 2015 it is unclear the best method of follow up following treatment of cervical intraepithelial neoplasia . Globally, 12% of women are positive for HPV DNA, with rates varying by age and country. The highest rates of HPV are in younger women, with a rate of 24% in women under 25 years. Rates decline in older age groups in Europe and the Americas, but less so in Africa and Asia. The rates are highest in Sub-Saharan Africa (24%) and Eastern Europe (21%) and lowest in North America (5%) and Western Asia (2%). The most common types of HPV worldwide are HPV16 (3.2%), HPV18 (1.4%), HPV52 (0.9%), HPV31 (0.8%), and HPV58 (0.7%). High-risk types of HPV are also distributed unevenly, with HPV16 having a rate around 13% in Africa and 30% in West and Central Asia. Like many diseases, HPV disproportionately affects low-income and resource-poor countries. The higher rates of HPV in Sub-Saharan Africa, for example, may be related to high exposure to human immunodeficiency virus (HIV) in the region. Other factors that impact the global spread of disease are sexual behaviors including age of sexual debut, number of sexual partners, and ease of access to barrier contraception, all of which vary globally. HPV is estimated to be the most common sexually transmitted infection in the United States. Most sexually active men and women will probably acquire genital HPV infection at some point in their lives. The American Social Health Association estimates that about 75–80% of sexually active Americans will be infected with HPV at some point in their lifetime. By the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV. It was estimated that, in the year 2000, there were approximately 6.2 million new HPV infections among Americans aged 15–44; of these, an estimated 74% occurred to people between ages of 15 and 24. Of the STIs studied, genital HPV was the most commonly acquired. In the United States, it is estimated that 10% of the population has an active HPV infection, 4% has an infection that has caused cytological abnormalities, and an additional 1% has an infection causing genital warts. Estimates of HPV prevalence vary from 14% to more than 90%. One reason for the difference is that some studies report women who currently have a detectable infection, while other studies report women who have ever had a detectable infection. Another cause of discrepancy is the difference in strains that were tested for. [ citation needed ] One study found that, during 2003–2004, at any given time , 26.8% of women aged 14 to 59 were infected with at least one type of HPV. This was higher than previous estimates; 15.2% were infected with one or more of the high-risk types that can cause cancer. The prevalence for high-risk and low-risk types is roughly similar over time. Human papillomavirus is not included among the diseases that are typically reportable to the CDC as of 2011. On average 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014. Cervical cancer was the most frequent HPV-associated cancer with on average 292 cases per year (74% of the female total, and 54% of the overall total of HPV-associated cancers). A study of 996 cervical cytology samples in an Irish urban female, opportunistically screened population, found an overall HPV prevalence of 19.8%, HPV 16 at 20% and HPV 18 at 12% were the commonest high-risk types detected. In Europe, types 16 and 18 are responsible for over 70% of cervical cancers. Overall rates of HPV-associated invasive cancers may be increasing. Between 1994 and 2014, there was a 2% increase in the rate of HPV-associated invasive cancers per year for both sexes in Ireland. As HPV is known to be associated with ano-genital warts, these are notifiable to the Health Protection Surveillance Centre (HPSC). Genital warts are the second most common STI in Ireland. There were 1,281 cases of ano-genital warts notified in 2017, which was a decrease on the 2016 figure of 1,593. The highest age-specific rate for both male and female was in the 25–29 year old age range; 53% of cases were among males. In Sri Lanka, the prevalence of HPV is 15.5% regardless of their cytological abnormalities. In the Autonomous Region of Inner Mongolia overall HPV prevalence is 14.5% but shows substantial ethnical disparity, the prevalence in Mongolian women (14.9%) being much higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian women. The region is thus an important example that epidemiology of HPV is more related to cultural and ethnical factors and not to geography per se. [ citation needed ]HPV is estimated to be the most common sexually transmitted infection in the United States. Most sexually active men and women will probably acquire genital HPV infection at some point in their lives. The American Social Health Association estimates that about 75–80% of sexually active Americans will be infected with HPV at some point in their lifetime. By the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV. It was estimated that, in the year 2000, there were approximately 6.2 million new HPV infections among Americans aged 15–44; of these, an estimated 74% occurred to people between ages of 15 and 24. Of the STIs studied, genital HPV was the most commonly acquired. In the United States, it is estimated that 10% of the population has an active HPV infection, 4% has an infection that has caused cytological abnormalities, and an additional 1% has an infection causing genital warts. Estimates of HPV prevalence vary from 14% to more than 90%. One reason for the difference is that some studies report women who currently have a detectable infection, while other studies report women who have ever had a detectable infection. Another cause of discrepancy is the difference in strains that were tested for. [ citation needed ] One study found that, during 2003–2004, at any given time , 26.8% of women aged 14 to 59 were infected with at least one type of HPV. This was higher than previous estimates; 15.2% were infected with one or more of the high-risk types that can cause cancer. The prevalence for high-risk and low-risk types is roughly similar over time. Human papillomavirus is not included among the diseases that are typically reportable to the CDC as of 2011. On average 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014. Cervical cancer was the most frequent HPV-associated cancer with on average 292 cases per year (74% of the female total, and 54% of the overall total of HPV-associated cancers). A study of 996 cervical cytology samples in an Irish urban female, opportunistically screened population, found an overall HPV prevalence of 19.8%, HPV 16 at 20% and HPV 18 at 12% were the commonest high-risk types detected. In Europe, types 16 and 18 are responsible for over 70% of cervical cancers. Overall rates of HPV-associated invasive cancers may be increasing. Between 1994 and 2014, there was a 2% increase in the rate of HPV-associated invasive cancers per year for both sexes in Ireland. As HPV is known to be associated with ano-genital warts, these are notifiable to the Health Protection Surveillance Centre (HPSC). Genital warts are the second most common STI in Ireland. There were 1,281 cases of ano-genital warts notified in 2017, which was a decrease on the 2016 figure of 1,593. The highest age-specific rate for both male and female was in the 25–29 year old age range; 53% of cases were among males. In Sri Lanka, the prevalence of HPV is 15.5% regardless of their cytological abnormalities. In the Autonomous Region of Inner Mongolia overall HPV prevalence is 14.5% but shows substantial ethnical disparity, the prevalence in Mongolian women (14.9%) being much higher than that of Han participants (4.3%). Urbanization, the number of sex partners, and PAP history appear as risk factors for HPV infection in Han, but not in Mongolian women. The region is thus an important example that epidemiology of HPV is more related to cultural and ethnical factors and not to geography per se. [ citation needed ]In 1972, the association of the human papillomaviruses with skin cancer in epidermodysplasia verruciformis was proposed by Stefania Jabłońska in Poland. In 1976 Harald zur Hausen published the hypothesis that human papilloma virus plays an important role in the cause of cervical cancer . In 1978, Jabłońska and Gerard Orth at the Pasteur Institute discovered HPV-5 in skin cancer . In 1983 and 1984 zur Hausen and his collaborators identified HPV16 and HPV18 in cervical cancer. The HeLa cell line contains extra DNA in its genome that originated from HPV type 18. The Ludwig-McGill HPV Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk. It was established in 1993 by Ludwig Cancer Research and McGill University in Montreal, Canada.

Wiki

Chikungunya

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

Measles

Measles is a highly contagious, vaccine-preventable infectious disease caused by measles virus . Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever , often greater than 40 °C (104 °F) , cough, runny nose , and inflamed eyes . Small white spots known as Koplik's spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea (in 8% of cases), middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression . Less commonly seizures , blindness , or inflammation of the brain may occur. Other names include morbilli , rubeola , red measles , and English measles . Both rubella , also known as German measles , and roseola are different diseases caused by unrelated viruses. Measles is an airborne disease which spreads easily from one person to the next through the coughs and sneezes of infected people. It may also be spread through direct contact with mouth or nasal secretions . It is extremely contagious: nine out of ten people who are not immune and share living space with an infected person will be infected. Furthermore, measles's reproductive number estimates vary beyond the frequently cited range of 12 to 18. The NIH quote this 2017 paper saying: "[a] review in 2017 identified feasible measles R 0 values of 3.7–203.3". People are infectious to others from four days before to four days after the start of the rash. While often regarded as a childhood illness, it can affect people of any age. Most people do not get the disease more than once. Testing for the measles virus in suspected cases is important for public health efforts. Measles is not known to occur in other animals. Once a person has become infected, no specific treatment is available, although supportive care may improve outcomes. Such care may include oral rehydration solution (slightly sweet and salty fluids), healthy food, and medications to control the fever. Antibiotics should be prescribed if secondary bacterial infections such as ear infections or pneumonia occur. Vitamin A supplementation is also recommended for children. Among cases reported in the U.S. between 1985 and 1992, death occurred in only 0.2% of cases, but may be up to 10% in people with malnutrition . Most of those who die from the infection are less than five years old. The measles vaccine is effective at preventing the disease, is exceptionally safe, and is often delivered in combination with other vaccines. Vaccination resulted in an 80% decrease in deaths from measles between 2000 and 2017, with about 85% of children worldwide having received their first dose as of 2017. Measles affects about 20 million people a year, primarily in the developing areas of Africa and Asia. It is one of the leading vaccine-preventable disease causes of death. In 1980, 2.6 million people died from measles, and in 1990, 545,000 died due to the disease; by 2014, global vaccination programs had reduced the number of deaths from measles to 73,000. Despite these trends, rates of disease and deaths increased from 2017 to 2019 due to a decrease in immunization. Symptoms typically begin 10–14 days after exposure. The classic symptoms include a four-day fever (the four Ds) and the three Cs— cough , coryza (head cold, fever, sneezing), and conjunctivitis (red eyes)—along with a maculopapular rash . Fever is common and typically lasts for about one week; the fever seen with measles is often as high as 40 °C (104 °F) . Koplik's spots seen inside the mouth are diagnostic for measles, but are temporary and therefore rarely seen. Koplik spots are small white spots that are commonly seen on the inside of the cheeks opposite the molars. They appear as "grains of salt on a reddish background." Recognizing these spots before a person reaches their maximum infectiousness can help reduce the spread of the disease. The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever starts. It starts on the back of the ears and, after a few hours, spreads to the head and neck before spreading to cover most of the body. The measles rash appears two to four days after the initial symptoms and lasts for up to eight days. The rash is said to "stain", changing color from red to dark brown, before disappearing. Overall, measles usually resolves after about three weeks. People who have been vaccinated against measles but have incomplete protective immunity may experience a form of modified measles. Modified measles is characterized by a prolonged incubation period , milder, and less characteristic symptoms (sparse and discrete rash of short duration). Complications of measles are relatively common, ranging from mild ones such as diarrhea to serious ones such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia ), laryngotracheobronchitis (croup) (either direct viral laryngotracheobronchitis or secondary bacterial bronchitis), otitis media , acute brain inflammation , corneal ulceration (leading to corneal scarring ), and in about 1 in 600 unvaccinated infants under 15 months while more rarely in older children and adults, subacute sclerosing panencephalitis , which is progressive and eventually lethal. In addition, measles can suppress the immune system for weeks to months, and this can contribute to bacterial superinfections such as otitis media and bacterial pneumonia. Two months after recovery there is a 11–73% decrease in the number of antibodies against other bacteria and viruses. The death rate in the 1920s was around 30% for measles pneumonia. People who are at high risk for complications are infants and children aged less than 5 years; adults aged over 20 years; pregnant women; people with compromised immune systems, such as from leukemia , HIV infection or innate immunodeficiency; and those who are malnourished or have vitamin A deficiency . Complications are usually more severe in adults. Between 1987 and 2000, the case fatality rate across the United States was three deaths per 1,000 cases attributable to measles, or 0.3%. In underdeveloped nations with high rates of malnutrition and poor healthcare , fatality rates have been as high as 28%. In immunocompromised persons (e.g., people with AIDS ) the fatality rate is approximately 30%. Even in previously healthy children, measles can cause serious illness requiring hospitalization. One out of every 1,000 measles cases progresses to acute encephalitis , which often results in permanent brain damage. One to three out of every 1,000 children who become infected with measles will die from respiratory and neurological complications. Complications of measles are relatively common, ranging from mild ones such as diarrhea to serious ones such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia ), laryngotracheobronchitis (croup) (either direct viral laryngotracheobronchitis or secondary bacterial bronchitis), otitis media , acute brain inflammation , corneal ulceration (leading to corneal scarring ), and in about 1 in 600 unvaccinated infants under 15 months while more rarely in older children and adults, subacute sclerosing panencephalitis , which is progressive and eventually lethal. In addition, measles can suppress the immune system for weeks to months, and this can contribute to bacterial superinfections such as otitis media and bacterial pneumonia. Two months after recovery there is a 11–73% decrease in the number of antibodies against other bacteria and viruses. The death rate in the 1920s was around 30% for measles pneumonia. People who are at high risk for complications are infants and children aged less than 5 years; adults aged over 20 years; pregnant women; people with compromised immune systems, such as from leukemia , HIV infection or innate immunodeficiency; and those who are malnourished or have vitamin A deficiency . Complications are usually more severe in adults. Between 1987 and 2000, the case fatality rate across the United States was three deaths per 1,000 cases attributable to measles, or 0.3%. In underdeveloped nations with high rates of malnutrition and poor healthcare , fatality rates have been as high as 28%. In immunocompromised persons (e.g., people with AIDS ) the fatality rate is approximately 30%. Even in previously healthy children, measles can cause serious illness requiring hospitalization. One out of every 1,000 measles cases progresses to acute encephalitis , which often results in permanent brain damage. One to three out of every 1,000 children who become infected with measles will die from respiratory and neurological complications. Measles is caused by the measles virus , a single-stranded, negative-sense , enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae . The virus is highly contagious and is spread by coughing and sneezing via close personal contact or direct contact with secretions. Measles is the most contagious virus known. It remains infective for up to two hours in that airspace or nearby surfaces. Measles is so contagious that if one person has it, 90% of non-immune people who have close contact with them (e.g., household members) will also become infected. Humans are the only natural hosts of the virus, and no other animal reservoirs are known to exist, although mountain gorillas are believed to be susceptible to the disease. Risk factors for measles virus infection include immunodeficiency caused by HIV/AIDS , immunosuppression following receipt of an organ or a stem cell transplant , alkylating agents , or corticosteroid therapy , regardless of immunization status; travel to areas where measles commonly occurs or contact with travelers from such an area; and the loss of passive, inherited antibodies before the age of routine immunization. Once the measles virus gets onto the mucosa , it infects the epithelial cells in the trachea or bronchi. Measles virus uses a protein on its surface called hemagglutinin (H protein), to bind to a target receptor on the host cell, which could be CD46 , which is expressed on all nucleated human cells, CD150 , aka signaling lymphocyte activation molecule or SLAM, which is found on immune cells like B or T cells, and antigen-presenting cells, or nectin-4 , a cellular adhesion molecule. Once bound, the fusion, or F protein helps the virus fuse with the membrane and ultimately get inside the cell. As the virus is a single-stranded negative-sense RNA virus , it includes the enzyme RNA-dependent RNA polymerase (RdRp) which is used to transcribe its genome into a positive-sense mRNA strand. After entering a cell, it is ready to be translated into viral proteins, wrapped in the cell's lipid envelope, and sent out of the cell as a newly made virus. Within days, the measles virus spreads through local tissue and is picked up by dendritic cells and alveolar macrophages , and carried from that local tissue in the lungs to the local lymph nodes. From there it continues to spread, eventually getting into the blood and spreading to more lung tissue, as well as other organs like the intestines and the brain. Functional impairment of the infected dendritic cells by the measles virus is thought to contribute to measles-induced immunosuppression. Typically, clinical diagnosis begins with the onset of fever and malaise about 10 days after exposure to the measles virus, followed by the emergence of cough , coryza , and conjunctivitis that worsen in severity over 4 days of appearing. Observation of Koplik's spots is also diagnostic. Other possible condition that can result in these symptoms include parvovirus , dengue fever , Kawasaki disease , and scarlet fever . Laboratory confirmation is, however, strongly recommended. Laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or detection of measles virus RNA from throat, nasal or urine specimen by using the reverse transcription polymerase chain reaction assay. This method is particularly useful to confirm cases when the IgM antibodies results are inconclusive. For people unable to have their blood drawn , saliva can be collected for salivary measles-specific IgA testing. Salivary tests used to diagnose measles involve collecting a saliva sample and testing for the presence of measles antibodies. This method is not ideal, as saliva contains many other fluids and proteins which may make it difficult to collect samples and detect measles antibodies. Saliva also contains 800 times fewer antibodies than blood samples do, which makes salivary testing additionally difficult. Positive contact with other people known to have measles adds evidence to the diagnosis. Laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or detection of measles virus RNA from throat, nasal or urine specimen by using the reverse transcription polymerase chain reaction assay. This method is particularly useful to confirm cases when the IgM antibodies results are inconclusive. For people unable to have their blood drawn , saliva can be collected for salivary measles-specific IgA testing. Salivary tests used to diagnose measles involve collecting a saliva sample and testing for the presence of measles antibodies. This method is not ideal, as saliva contains many other fluids and proteins which may make it difficult to collect samples and detect measles antibodies. Saliva also contains 800 times fewer antibodies than blood samples do, which makes salivary testing additionally difficult. Positive contact with other people known to have measles adds evidence to the diagnosis. Mothers who are immune to measles pass antibodies to their children while they are still in the womb, especially if the mother acquired immunity through infection rather than vaccination. Such antibodies will usually give newborn infants some immunity against measles, but these antibodies are gradually lost over the course of the first nine months of life. Infants under one year of age whose maternal anti-measles antibodies have disappeared become susceptible to infection with the measles virus. In developed countries, it is recommended that children be immunized against measles at 12 months, generally as part of a three-part MMR vaccine (measles, mumps , and rubella ). The vaccine is generally not given before this age because such infants respond inadequately to the vaccine due to an immature immune system. A second dose of the vaccine is usually given to children between the ages of four and five, to increase rates of immunity. Measles vaccines have been given to over a billion people. Vaccination rates have been high enough to make measles relatively uncommon. Adverse reactions to vaccination are rare, with fever and pain at the injection site being the most common. Life-threatening adverse reactions occur in less than one per million vaccinations (<0.0001%). In developing countries where measles is common , the World Health Organization (WHO) recommends two doses of vaccine be given, at six and nine months of age. The vaccine should be given whether the child is HIV-infected or not. The vaccine is less effective in HIV-infected infants than in the general population, but early treatment with antiretroviral drugs can increase its effectiveness. Measles vaccination programs are often used to deliver other child health interventions as well, such as bed nets to protect against malaria , antiparasite medicine and vitamin A supplements, and so contribute to the reduction of child deaths from other causes. The Advisory Committee on Immunization Practices (ACIP) recommends that all adult international travelers who do not have positive evidence of previous measles immunity receive two doses of MMR vaccine before traveling, although birth before 1957 is presumptive evidence of immunity. Those born in the United States before 1957 are likely to have been naturally infected with measles virus and generally need not be considered susceptible. There have been false claims of an association between the measles vaccine and autism ; this incorrect concern has reduced the rate of vaccination and increased the number of cases of measles where immunization rates became too low to maintain herd immunity . Additionally, there have been false claims that measles infection protects against cancer. Administration of the MMR vaccine may prevent measles after exposure to the virus (post-exposure prophylaxis). Post-exposure prophylaxis guidelines are specific to jurisdiction and population. Passive immunization against measles by an intramuscular injection of antibodies could be effective up to the seventh day after exposure. Compared to no treatment, the risk of measles infection is reduced by 83%, and the risk of death by measles is reduced by 76%. However, the effectiveness of passive immunization in comparison to active measles vaccine is not clear. The MMR vaccine is 95% effective for preventing measles after one dose if the vaccine is given to a child who is 12 months or older; if a second dose of the MMR vaccine is given, it will provide immunity in 99% of children. There is no evidence that the measles vaccine virus can be transmitted to other persons. There is no specific antiviral treatment if measles develops. Instead the medications are generally aimed at treating superinfections, maintaining good hydration with adequate fluids, and pain relief. Some groups, like young children and the severely malnourished, are also given vitamin A , which acts as an immunomodulator that boosts the antibody responses to measles and decreases the risk of serious complications. Treatment is supportive , with ibuprofen or paracetamol (acetaminophen) to reduce fever and pain and, if required, a fast-acting medication to dilate the airways for cough. As for aspirin , some research has suggested a correlation between children who take aspirin and the development of Reye syndrome . The use of vitamin A during treatment is recommended to decrease the risk of blindness; however, it does not prevent or cure the disease. A systematic review of trials into its use found no reduction in overall mortality, but two doses (200,000 IU ) of vitamin A was shown to reduce mortality for measles in children younger than two years of age. It is unclear if zinc supplementation in children with measles affects outcomes as it has not been sufficiently studied. There are no adequate studies on whether Chinese medicinal herbs are effective. Treatment is supportive , with ibuprofen or paracetamol (acetaminophen) to reduce fever and pain and, if required, a fast-acting medication to dilate the airways for cough. As for aspirin , some research has suggested a correlation between children who take aspirin and the development of Reye syndrome . The use of vitamin A during treatment is recommended to decrease the risk of blindness; however, it does not prevent or cure the disease. A systematic review of trials into its use found no reduction in overall mortality, but two doses (200,000 IU ) of vitamin A was shown to reduce mortality for measles in children younger than two years of age. It is unclear if zinc supplementation in children with measles affects outcomes as it has not been sufficiently studied. There are no adequate studies on whether Chinese medicinal herbs are effective. Most people survive measles, though in some cases, complications may occur. About 1 in 4 individuals will be hospitalized and 1–2 in 1,000 will die. Complications are more likely in children under age 5 and adults over age 20. Pneumonia is the most common fatal complication of measles infection and accounts for 56–86% of measles-related deaths. Possible consequences of measles virus infection include laryngotracheobronchitis , sensorineural hearing loss , and—in about 1 in 10,000 to 1 in 300,000 cases — panencephalitis , which is usually fatal. Acute measles encephalitis is another serious risk of measles virus infection. It typically occurs two days to one week after the measles rash breaks out and begins with very high fever, severe headache, convulsions and altered mentation. A person with measles encephalitis may become comatose , and death or brain injury may occur. For people having had measles, it is rare to ever have a symptomatic reinfection. The measles virus can deplete previously acquired immune memory by killing cells that make antibodies, and thus weakens the immune system, which can cause deaths from other diseases. Suppression of the immune system by measles lasts about two years and has been epidemiologically implicated in up to 90% of childhood deaths in third world countries, and historically may have caused rather more deaths in the United States, the UK and Denmark than were directly caused by measles. Although the measles vaccine contains an attenuated strain, it does not deplete immune memory. Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities that generate insufficient new hosts the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is around 250,000. To achieve herd immunity , more than 95% of the community must be vaccinated due to the ease with which measles is transmitted from person to person. In 2011, the WHO estimated that 158,000 deaths were caused by measles. This is down from 630,000 deaths in 1990. As of 2018, measles remains a leading cause of vaccine-preventable deaths in the world. In developed countries the mortality rate is lower, for example in England and Wales from 2007 to 2017 death occurred between two and three cases out of 10,000. In children one to three cases out of every 1,000 die in the United States (0.1–0.2%). In populations with high levels of malnutrition and a lack of adequate healthcare, mortality can be as high as 10%. In cases with complications, the rate may rise to 20–30%. [ medical citation needed ] In 2012, the number of deaths due to measles was 78% lower than in 2000 due to increased rates of immunization among UN member states . Even in countries where vaccination has been introduced, rates may remain high. Measles is a leading cause of vaccine-preventable childhood mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in the Measles Initiative : the American Red Cross , the United States CDC , the United Nations Foundation , UNICEF and the WHO. Globally, measles fell 60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005. Estimates for 2008 indicate deaths fell further to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the Southeast Asian region. There were 142,300 measles related deaths globally in 2018, of which most cases were reported from African and eastern Mediterranean regions. These estimates were slightly higher than that of 2017, when 124,000 deaths were reported due to measles infection globally. In 2000, the WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide laboratory surveillance for measles, rubella , and congenital rubella syndrome . Data from 2016 to 2018 show that the most frequently detected measles virus genotypes are decreasing, suggesting that increasing global population immunity has decreased the number of chains of transmission. Cases reported in the first three months of 2019, were 300% higher than in the first three months of 2018, with outbreaks in every region of the world, even in countries with high overall vaccination coverage where it spread among clusters of unvaccinated people. The numbers of reported cases as of mid-November is over 413,000 globally, with an additional 250,000 cases in DRC (as reported through their national system), similar to the increasing trends of infection reported in the earlier months of 2019, compared to 2018. In 2019, the total number of cases worldwide climbed to 869,770. The number of cases reported for 2020 is lower compare to 2019. According to the WHO, the COVID-19 pandemic hindered vaccination campaigns in at least 68 countries, including in countries that were experiencing outbreaks, which caused increased risk of additional cases. In February 2024, the World Health Organization said more than half of the world was at risk of a measles outbreak due to Covid-19 pandemic-related disruptions in that month. All the world regions have reported such outbreaks with the exception of the Americas , though these could still be expected to become hotspots in the future. Death rates during the outbreaks tend to be higher among poorer countries but middle income nations are also heavily impacted, according to the WHO. In England and Wales, though deaths from measles were uncommon, they averaged about 500 per year in the 1940s. Deaths diminished with the improvement of medical care in the 1950s but the incidence of the disease did not retreat until vaccination was introduced in the late 1960s. Wider coverage was achieved in the 1980s with the measles, mumps and rubella , MMR vaccine . In 2013–14, there were almost 10,000 cases in 30 European countries. Most cases occurred in unvaccinated individuals and over 90% of cases occurred in Germany, Italy, Netherlands, Romania, and United Kingdom. Between October 2014 and March 2015, a measles outbreak in the German capital of Berlin resulted in at least 782 cases. In 2017, numbers continued to increase in Europe to 21,315 cases, with 35 deaths. In preliminary figures for 2018, reported cases in the region increased 3-fold to 82,596 in 47 countries, with 72 deaths; Ukraine had the most cases (53,218), with the highest incidence rates being in Ukraine (1209 cases per million), Serbia (579), Georgia (564) and Albania (500). The previous year (2017) saw an estimated measles vaccine coverage of 95% for the first dose and 90% for the second dose in the region, the latter figure being the highest-ever estimated second-dose coverage. In 2019, the United Kingdom, Albania, the Czech Republic, and Greece lost their measles-free status due to ongoing and prolonged spread of the disease in these countries. In the first 6 months of 2019, 90,000 cases occurred in Europe. As a result of widespread vaccination, the disease was declared eliminated from the Americas in 2016. However, there were cases again in 2017, 2018, 2019, and 2020 in this region. In the United States, measles affected approximately 3,000 people per million in the 1960s before the vaccine was available. With consistent widespread childhood vaccination, this figure fell to 13 cases per million by the 1980s, and to about 1 case per million by 2000. In 1991, an outbreak of measles in Philadelphia was centered at the Faith Tabernacle Congregation, a faith healing church that actively discouraged parishioners from vaccinating their children. Over 1400 people were infected with measles and nine children died. Before immunization in the United States, between three and four million cases occurred each year. The United States was declared free of circulating measles in 2000, with 911 cases from 2001 to 2011. In 2014 the CDC said endemic measles, rubella, and congenital rubella syndrome had not returned to the United States. Occasional measles outbreaks persist, however, because of cases imported from abroad, of which more than half are the result of unvaccinated U.S. residents who are infected abroad and infect others upon return to the United States. The CDC continues to recommend measles vaccination throughout the population to prevent outbreaks like these. In 2014, an outbreak was initiated in Ohio when two unvaccinated Amish men harboring asymptomatic measles returned to the United States from missionary work in the Philippines. Their return to a community with low vaccination rates led to an outbreak that rose to include a total of 383 cases across nine counties. Of the 383 cases, 340 (89%) occurred in unvaccinated individuals. From 4 January, to 2 April 2015, there were 159 cases of measles reported to the CDC. Of those 159 cases, 111 (70%) were determined to have come from an earlier exposure in late December 2014. This outbreak was believed to have originated from the Disneyland theme park in California. The Disneyland outbreak was held responsible for the infection of 147 people in seven U.S. states as well as Mexico and Canada, the majority of which were either unvaccinated or had unknown vaccination status. Of the cases 48% were unvaccinated and 38% were unsure of their vaccination status. The initial exposure to the virus was never identified. In 2015, a U.S. woman in Washington state died of pneumonia , as a result of measles. She was the first fatality in the U.S. from measles since 2003. The woman had been vaccinated for measles and was taking immunosuppressive drugs for another condition. The drugs suppressed the woman's immunity to measles, and the woman became infected with measles; she did not develop a rash, but contracted pneumonia, which caused her death. In June 2017, the Maine Health and Environmental Testing Laboratory confirmed a case of measles in Franklin County. This instance marks the first case of measles in 20 years for the state of Maine. In 2018, one case occurred in Portland, Oregon, with 500 people exposed; 40 of them lacked immunity to the virus and were being monitored by county health officials as of 2 July 2018. There were 273 cases of measles reported throughout the United States in 2018, including an outbreak in Brooklyn with more than 200 reported cases from October 2018 to February 2019. The outbreak was tied with population density of the Orthodox Jewish community, with the initial exposure from an unvaccinated child that caught measles while visiting Israel. A resurgence of measles occurred during 2019, which has been generally tied to parents choosing not to have their children vaccinated as most of the reported cases have occurred in people 19 years old or younger. Cases were first reported in Washington state in January, with an outbreak of at least 58 confirmed cases most within Clark County , which has a higher rate of vaccination exemptions compared to the rest of the state; nearly one in four kindergartners in Clark did not receive vaccinations, according to state data. This led Washington state governor Jay Inslee to declare a state of emergency, and the state's congress to introduce legislation to disallow vaccination exemption for personal or philosophical reasons. In April 2019, New York Mayor Bill de Blasio declared a public health emergency because of "a huge spike" in cases of measles where there were 285 cases centred on the Orthodox Jewish areas of Brooklyn in 2018, while there were only two cases in 2017. There were 168 more in neighboring Rockland County . Other outbreaks have included Santa Cruz County and Butte County in California, and the states of New Jersey and Michigan. As of April 2019 [ update ] , there have been 695 cases of measles reported in 22 states. This is the highest number of measles cases since it was declared eradicated in 2000. From 1 January, to 31 December 2019, 1,282 individual cases of measles were confirmed in 31 states. This is the greatest number of cases reported in the U.S. since 1992. Of the 1,282 cases, 128 of the people who got measles were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. Following the end of the 2019 outbreak, reported cases have fallen to pre-outbreak levels: 13 cases in 2020, 49 cases in 2021, and 121 cases in 2022. The spread of measles had been interrupted in Brazil in 2016, with the last-known case twelve months earlier. This last case was in the state of Ceará . Brazil won a measles elimination certificate by the Pan American Health Organization in 2016, but the Ministry of Health has proclaimed that the country has struggled to keep this certificate, since two outbreaks had already been identified in 2018, one in the state of Amazonas and another one in Roraima , in addition to cases in other states ( Rio de Janeiro , Rio Grande do Sul , Pará , São Paulo and Rondônia ), totaling 1,053 confirmed cases until 1 August 2018. In these outbreaks, and in most other cases, the contagion was related to the importation of the virus, especially from Venezuela. This was confirmed by the genotype of the virus (D8) that was identified, which is the same that circulates in Venezuela. In the Vietnamese measles epidemic in spring of 2014, an estimated 8,500 measles cases were reported as of 19 April, with 114 fatalities; as of 30 May, 21,639 suspected measles cases had been reported, with 142 measles-related fatalities. In the Naga Self-Administered Zone in a remote northern region of Myanmar , at least 40 children died during a measles outbreak in August 2016 that was probably caused by lack of vaccination in an area of poor health infrastructure. Following the 2019 Philippines measles outbreak , 23,563 measles cases have been reported in the country with 338 fatalities. A measles outbreak also happened among the Malaysian Orang Asli sub-group of Batek people in the state of Kelantan from May 2019, causing the deaths of 15 from the tribe. In 2024, a measles outbreak was declared in the Bangsamoro region in the Philippines with at least 592 cases and 3 deaths. A measles outbreak in New Zealand has 2193 confirmed cases and two deaths. A measles outbreak in Tonga has 612 cases of measles. A measles outbreak in Samoa in late 2019 has over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,000. Over three percent of the population were infected, and a state of emergency was declared from 17 November to 7 December. A vaccination campaign brought the measles vaccination rate from 31 to 34% in 2018 to an estimated 94% of the eligible population in December 2019. The Democratic Republic of the Congo and Madagascar have reported the highest numbers of cases in 2019. However, cases have decreased in Madagascar as a result of nationwide emergency measles vaccine campaigns. As of August 2019 outbreaks were occurring in Angola, Cameroon, Chad, Nigeria, South Sudan and Sudan. An outbreak of measles in 2018 has resulted in well beyond 115,000 cases and over 1,200 deaths. An outbreak of measles with nearly 5,000 deaths and 250,000 infections occurred in 2019, after the disease spread to all the provinces in the country. Most deaths were among children under five years of age. The World Health Organization (WHO) has reported this as the world's largest and fastest-moving epidemic. In England and Wales, though deaths from measles were uncommon, they averaged about 500 per year in the 1940s. Deaths diminished with the improvement of medical care in the 1950s but the incidence of the disease did not retreat until vaccination was introduced in the late 1960s. Wider coverage was achieved in the 1980s with the measles, mumps and rubella , MMR vaccine . In 2013–14, there were almost 10,000 cases in 30 European countries. Most cases occurred in unvaccinated individuals and over 90% of cases occurred in Germany, Italy, Netherlands, Romania, and United Kingdom. Between October 2014 and March 2015, a measles outbreak in the German capital of Berlin resulted in at least 782 cases. In 2017, numbers continued to increase in Europe to 21,315 cases, with 35 deaths. In preliminary figures for 2018, reported cases in the region increased 3-fold to 82,596 in 47 countries, with 72 deaths; Ukraine had the most cases (53,218), with the highest incidence rates being in Ukraine (1209 cases per million), Serbia (579), Georgia (564) and Albania (500). The previous year (2017) saw an estimated measles vaccine coverage of 95% for the first dose and 90% for the second dose in the region, the latter figure being the highest-ever estimated second-dose coverage. In 2019, the United Kingdom, Albania, the Czech Republic, and Greece lost their measles-free status due to ongoing and prolonged spread of the disease in these countries. In the first 6 months of 2019, 90,000 cases occurred in Europe. As a result of widespread vaccination, the disease was declared eliminated from the Americas in 2016. However, there were cases again in 2017, 2018, 2019, and 2020 in this region. In the United States, measles affected approximately 3,000 people per million in the 1960s before the vaccine was available. With consistent widespread childhood vaccination, this figure fell to 13 cases per million by the 1980s, and to about 1 case per million by 2000. In 1991, an outbreak of measles in Philadelphia was centered at the Faith Tabernacle Congregation, a faith healing church that actively discouraged parishioners from vaccinating their children. Over 1400 people were infected with measles and nine children died. Before immunization in the United States, between three and four million cases occurred each year. The United States was declared free of circulating measles in 2000, with 911 cases from 2001 to 2011. In 2014 the CDC said endemic measles, rubella, and congenital rubella syndrome had not returned to the United States. Occasional measles outbreaks persist, however, because of cases imported from abroad, of which more than half are the result of unvaccinated U.S. residents who are infected abroad and infect others upon return to the United States. The CDC continues to recommend measles vaccination throughout the population to prevent outbreaks like these. In 2014, an outbreak was initiated in Ohio when two unvaccinated Amish men harboring asymptomatic measles returned to the United States from missionary work in the Philippines. Their return to a community with low vaccination rates led to an outbreak that rose to include a total of 383 cases across nine counties. Of the 383 cases, 340 (89%) occurred in unvaccinated individuals. From 4 January, to 2 April 2015, there were 159 cases of measles reported to the CDC. Of those 159 cases, 111 (70%) were determined to have come from an earlier exposure in late December 2014. This outbreak was believed to have originated from the Disneyland theme park in California. The Disneyland outbreak was held responsible for the infection of 147 people in seven U.S. states as well as Mexico and Canada, the majority of which were either unvaccinated or had unknown vaccination status. Of the cases 48% were unvaccinated and 38% were unsure of their vaccination status. The initial exposure to the virus was never identified. In 2015, a U.S. woman in Washington state died of pneumonia , as a result of measles. She was the first fatality in the U.S. from measles since 2003. The woman had been vaccinated for measles and was taking immunosuppressive drugs for another condition. The drugs suppressed the woman's immunity to measles, and the woman became infected with measles; she did not develop a rash, but contracted pneumonia, which caused her death. In June 2017, the Maine Health and Environmental Testing Laboratory confirmed a case of measles in Franklin County. This instance marks the first case of measles in 20 years for the state of Maine. In 2018, one case occurred in Portland, Oregon, with 500 people exposed; 40 of them lacked immunity to the virus and were being monitored by county health officials as of 2 July 2018. There were 273 cases of measles reported throughout the United States in 2018, including an outbreak in Brooklyn with more than 200 reported cases from October 2018 to February 2019. The outbreak was tied with population density of the Orthodox Jewish community, with the initial exposure from an unvaccinated child that caught measles while visiting Israel. A resurgence of measles occurred during 2019, which has been generally tied to parents choosing not to have their children vaccinated as most of the reported cases have occurred in people 19 years old or younger. Cases were first reported in Washington state in January, with an outbreak of at least 58 confirmed cases most within Clark County , which has a higher rate of vaccination exemptions compared to the rest of the state; nearly one in four kindergartners in Clark did not receive vaccinations, according to state data. This led Washington state governor Jay Inslee to declare a state of emergency, and the state's congress to introduce legislation to disallow vaccination exemption for personal or philosophical reasons. In April 2019, New York Mayor Bill de Blasio declared a public health emergency because of "a huge spike" in cases of measles where there were 285 cases centred on the Orthodox Jewish areas of Brooklyn in 2018, while there were only two cases in 2017. There were 168 more in neighboring Rockland County . Other outbreaks have included Santa Cruz County and Butte County in California, and the states of New Jersey and Michigan. As of April 2019 [ update ] , there have been 695 cases of measles reported in 22 states. This is the highest number of measles cases since it was declared eradicated in 2000. From 1 January, to 31 December 2019, 1,282 individual cases of measles were confirmed in 31 states. This is the greatest number of cases reported in the U.S. since 1992. Of the 1,282 cases, 128 of the people who got measles were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. Following the end of the 2019 outbreak, reported cases have fallen to pre-outbreak levels: 13 cases in 2020, 49 cases in 2021, and 121 cases in 2022. The spread of measles had been interrupted in Brazil in 2016, with the last-known case twelve months earlier. This last case was in the state of Ceará . Brazil won a measles elimination certificate by the Pan American Health Organization in 2016, but the Ministry of Health has proclaimed that the country has struggled to keep this certificate, since two outbreaks had already been identified in 2018, one in the state of Amazonas and another one in Roraima , in addition to cases in other states ( Rio de Janeiro , Rio Grande do Sul , Pará , São Paulo and Rondônia ), totaling 1,053 confirmed cases until 1 August 2018. In these outbreaks, and in most other cases, the contagion was related to the importation of the virus, especially from Venezuela. This was confirmed by the genotype of the virus (D8) that was identified, which is the same that circulates in Venezuela. In the United States, measles affected approximately 3,000 people per million in the 1960s before the vaccine was available. With consistent widespread childhood vaccination, this figure fell to 13 cases per million by the 1980s, and to about 1 case per million by 2000. In 1991, an outbreak of measles in Philadelphia was centered at the Faith Tabernacle Congregation, a faith healing church that actively discouraged parishioners from vaccinating their children. Over 1400 people were infected with measles and nine children died. Before immunization in the United States, between three and four million cases occurred each year. The United States was declared free of circulating measles in 2000, with 911 cases from 2001 to 2011. In 2014 the CDC said endemic measles, rubella, and congenital rubella syndrome had not returned to the United States. Occasional measles outbreaks persist, however, because of cases imported from abroad, of which more than half are the result of unvaccinated U.S. residents who are infected abroad and infect others upon return to the United States. The CDC continues to recommend measles vaccination throughout the population to prevent outbreaks like these. In 2014, an outbreak was initiated in Ohio when two unvaccinated Amish men harboring asymptomatic measles returned to the United States from missionary work in the Philippines. Their return to a community with low vaccination rates led to an outbreak that rose to include a total of 383 cases across nine counties. Of the 383 cases, 340 (89%) occurred in unvaccinated individuals. From 4 January, to 2 April 2015, there were 159 cases of measles reported to the CDC. Of those 159 cases, 111 (70%) were determined to have come from an earlier exposure in late December 2014. This outbreak was believed to have originated from the Disneyland theme park in California. The Disneyland outbreak was held responsible for the infection of 147 people in seven U.S. states as well as Mexico and Canada, the majority of which were either unvaccinated or had unknown vaccination status. Of the cases 48% were unvaccinated and 38% were unsure of their vaccination status. The initial exposure to the virus was never identified. In 2015, a U.S. woman in Washington state died of pneumonia , as a result of measles. She was the first fatality in the U.S. from measles since 2003. The woman had been vaccinated for measles and was taking immunosuppressive drugs for another condition. The drugs suppressed the woman's immunity to measles, and the woman became infected with measles; she did not develop a rash, but contracted pneumonia, which caused her death. In June 2017, the Maine Health and Environmental Testing Laboratory confirmed a case of measles in Franklin County. This instance marks the first case of measles in 20 years for the state of Maine. In 2018, one case occurred in Portland, Oregon, with 500 people exposed; 40 of them lacked immunity to the virus and were being monitored by county health officials as of 2 July 2018. There were 273 cases of measles reported throughout the United States in 2018, including an outbreak in Brooklyn with more than 200 reported cases from October 2018 to February 2019. The outbreak was tied with population density of the Orthodox Jewish community, with the initial exposure from an unvaccinated child that caught measles while visiting Israel. A resurgence of measles occurred during 2019, which has been generally tied to parents choosing not to have their children vaccinated as most of the reported cases have occurred in people 19 years old or younger. Cases were first reported in Washington state in January, with an outbreak of at least 58 confirmed cases most within Clark County , which has a higher rate of vaccination exemptions compared to the rest of the state; nearly one in four kindergartners in Clark did not receive vaccinations, according to state data. This led Washington state governor Jay Inslee to declare a state of emergency, and the state's congress to introduce legislation to disallow vaccination exemption for personal or philosophical reasons. In April 2019, New York Mayor Bill de Blasio declared a public health emergency because of "a huge spike" in cases of measles where there were 285 cases centred on the Orthodox Jewish areas of Brooklyn in 2018, while there were only two cases in 2017. There were 168 more in neighboring Rockland County . Other outbreaks have included Santa Cruz County and Butte County in California, and the states of New Jersey and Michigan. As of April 2019 [ update ] , there have been 695 cases of measles reported in 22 states. This is the highest number of measles cases since it was declared eradicated in 2000. From 1 January, to 31 December 2019, 1,282 individual cases of measles were confirmed in 31 states. This is the greatest number of cases reported in the U.S. since 1992. Of the 1,282 cases, 128 of the people who got measles were hospitalized, and 61 reported having complications, including pneumonia and encephalitis. Following the end of the 2019 outbreak, reported cases have fallen to pre-outbreak levels: 13 cases in 2020, 49 cases in 2021, and 121 cases in 2022. The spread of measles had been interrupted in Brazil in 2016, with the last-known case twelve months earlier. This last case was in the state of Ceará . Brazil won a measles elimination certificate by the Pan American Health Organization in 2016, but the Ministry of Health has proclaimed that the country has struggled to keep this certificate, since two outbreaks had already been identified in 2018, one in the state of Amazonas and another one in Roraima , in addition to cases in other states ( Rio de Janeiro , Rio Grande do Sul , Pará , São Paulo and Rondônia ), totaling 1,053 confirmed cases until 1 August 2018. In these outbreaks, and in most other cases, the contagion was related to the importation of the virus, especially from Venezuela. This was confirmed by the genotype of the virus (D8) that was identified, which is the same that circulates in Venezuela. In the Vietnamese measles epidemic in spring of 2014, an estimated 8,500 measles cases were reported as of 19 April, with 114 fatalities; as of 30 May, 21,639 suspected measles cases had been reported, with 142 measles-related fatalities. In the Naga Self-Administered Zone in a remote northern region of Myanmar , at least 40 children died during a measles outbreak in August 2016 that was probably caused by lack of vaccination in an area of poor health infrastructure. Following the 2019 Philippines measles outbreak , 23,563 measles cases have been reported in the country with 338 fatalities. A measles outbreak also happened among the Malaysian Orang Asli sub-group of Batek people in the state of Kelantan from May 2019, causing the deaths of 15 from the tribe. In 2024, a measles outbreak was declared in the Bangsamoro region in the Philippines with at least 592 cases and 3 deaths. A measles outbreak in New Zealand has 2193 confirmed cases and two deaths. A measles outbreak in Tonga has 612 cases of measles. A measles outbreak in Samoa in late 2019 has over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,000. Over three percent of the population were infected, and a state of emergency was declared from 17 November to 7 December. A vaccination campaign brought the measles vaccination rate from 31 to 34% in 2018 to an estimated 94% of the eligible population in December 2019. A measles outbreak in Samoa in late 2019 has over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,000. Over three percent of the population were infected, and a state of emergency was declared from 17 November to 7 December. A vaccination campaign brought the measles vaccination rate from 31 to 34% in 2018 to an estimated 94% of the eligible population in December 2019. The Democratic Republic of the Congo and Madagascar have reported the highest numbers of cases in 2019. However, cases have decreased in Madagascar as a result of nationwide emergency measles vaccine campaigns. As of August 2019 outbreaks were occurring in Angola, Cameroon, Chad, Nigeria, South Sudan and Sudan. An outbreak of measles in 2018 has resulted in well beyond 115,000 cases and over 1,200 deaths. An outbreak of measles with nearly 5,000 deaths and 250,000 infections occurred in 2019, after the disease spread to all the provinces in the country. Most deaths were among children under five years of age. The World Health Organization (WHO) has reported this as the world's largest and fastest-moving epidemic. An outbreak of measles in 2018 has resulted in well beyond 115,000 cases and over 1,200 deaths. An outbreak of measles with nearly 5,000 deaths and 250,000 infections occurred in 2019, after the disease spread to all the provinces in the country. Most deaths were among children under five years of age. The World Health Organization (WHO) has reported this as the world's largest and fastest-moving epidemic. Measles is of zoonotic origin, having evolved from rinderpest , which infects cattle. A precursor of the measles began causing infections in humans as early as the 4th century BC or as late as after 500 AD. The Antonine Plague of 165–180 AD has been speculated to have been measles, but the actual cause of this plague is unknown and smallpox is a more likely cause. The first systematic description of measles, and its distinction from smallpox and chickenpox , is credited to the Persian physician Muhammad ibn Zakariya al-Razi (860–932), who published The Book of Smallpox and Measles . At the time of Razi's book, it is believed that outbreaks were still limited and that the virus was not fully adapted to humans. Sometime between 1100 and 1200 AD, the measles virus fully diverged from rinderpest, becoming a distinct virus that infects humans. This agrees with the observation that measles requires a susceptible population of over 500,000 to sustain an epidemic, a situation that occurred in historic times following the growth of medieval European cities. Measles is an endemic disease , meaning it has been continually present in a community and many people develop resistance. In populations not exposed to measles, exposure to the new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of those indigenous people who had previously survived smallpox. Two years later, measles was responsible for the deaths of half the population of Honduras , and it has ravaged Mexico , Central America , and the Inca civilization. Between roughly 1855 and 2005, measles is estimated to have killed about 200 million people worldwide. The 1846 measles outbreak in the Faroe Islands was unusual for being well studied. Measles had not been seen on the islands for 60 years, so almost no residents had any acquired immunity. Three-quarters of the residents got sick, and more than 100 (1–2%) died from it before the epidemic burned itself out. Peter Ludvig Panum observed the outbreak and determined that measles was spread through direct contact of contagious people with people who had never had measles. Measles killed 20 percent of Hawaii 's population in the 1850s. In 1875, measles killed over 40,000 Fijians , approximately one-third of the population. In the 19th century, the disease killed more than half of the Great Andamanese population. [ better source needed ] Seven to eight million children are thought to have died from measles each year before the vaccine was introduced. In 1914, a statistician for the Prudential Insurance Company estimated from a survey of 22 countries that 1% of all deaths in the temperate zone were caused by measles. He observed also that 1–6% of cases of measles ended fatally, the difference depending on age (0–3 being the worst), social conditions (e.g. overcrowded tenements) and pre-existing health conditions. In 1954, the virus causing the disease was isolated from a 13-year-old boy from the United States, David Edmonston, and adapted and propagated on chick embryo tissue culture . The World Health Organization recognizes eight clades , named A, B, C, D, E, F, G, and H. Twenty-three strains of the measles virus have been identified and designated within these clades. While at Merck , Maurice Hilleman developed the first successful vaccine. Licensed vaccines to prevent the disease became available in 1963. An improved measles vaccine became available in 1968. Measles as an endemic disease was eliminated from the United States in 2000, but continues to be reintroduced by international travelers. In 2019 there were at least 1,241 cases of measles in the United States distributed across 31 states, with over three quarters in New York. German anti-vaccination campaigner and HIV/AIDS denialist Stefan Lanka posed a challenge on his website in 2011, offering a sum of €100,000 for anyone who could scientifically prove that measles is caused by a virus and determine the diameter of the virus. He posited that the illness is psychosomatic and that the measles virus does not exist. When provided with overwhelming scientific evidence from various medical studies by German physician David Bardens , Lanka did not accept the findings, forcing Bardens to appeal in court. The initial legal case ended with the ruling that Lanka was to pay the prize. However, on appeal, Lanka was ultimately not required to pay the award because the submitted evidence did not meet his exact requirements. The case received wide international coverage that prompted many to comment on it, including neurologist , well-known skeptic and science-based medicine advocate Steven Novella , who called Lanka "a crank". As outbreaks easily occur in under-vaccinated populations, the disease is seen as a test of sufficient vaccination within a population. Measles outbreaks have been on the rise in the United States, especially in communities with lower rates of vaccination. A different vaccine distribution within a single territory by age or social class may define different general perceptions of vaccination efficacy. It is often introduced to a region by travelers from other countries and it typically spreads to those who have not received the measles vaccination. Other names include morbilli, rubeola, red measles, and English measles. Other names include morbilli, rubeola, red measles, and English measles. In May 2015, the journal Science published a report in which researchers found that the measles infection can leave a population at increased risk for mortality from other diseases for two to three years. Results from additional studies that show the measles virus can kill cells that make antibodies were published in November 2019. A specific drug treatment for measles, ERDRP-0519 , has shown [ when? ] promising results in animal studies, but has not yet [ when? ] been tested in humans.

Wiki

Chikungunya

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

Aedes

List of Aedes species Aedes (also known as the tiger mosquito ) is a genus of mosquitoes originally found in tropical and subtropical zones , but now found on all continents except Antarctica . Some species have been spread by human activity : Aedes albopictus , a particularly invasive species , was spread to the Americas , including the United States , in the 1980s, by the used-tire trade . First described and named by German entomologist Johann Wilhelm Meigen in 1818, the generic name comes from the Ancient Greek ἀηδής , aēdēs , meaning 'unpleasant' or 'odious'. The type species for Aedes is Aedes cinereus . The genus was named by Johann Wilhelm Meigen in 1818. The generic name comes from the Ancient Greek ἀηδής , aēdēs , meaning 'unpleasant' or 'odious'. As historically defined, the genus contains over 700 species (see the list of Aedes species ). The genus has been divided into several subgenera ( Aedes , Diceromyia , Finlaya , Stegomyia , etc.), most of which have been recently treated by some authorities as full genera. The classification was revised in 2009. Aedes mosquitoes are visually distinctive because they have noticeable black and white markings on their bodies and legs. Unlike most other mosquitoes, they are active and bite only during the daytime . The peak biting periods are early in the morning and in the evening before dusk. The genus contains 28 species that are not placed in a further subgenus: Members of the genus Aedes are known vectors for numerous viral infections, including dengue fever , yellow fever , the Zika virus , and chikungunya , which are transmitted by species in the subgenus Stegomyia , and by A. aegypti and A. albopictus . Infections with these viruses are typically accompanied by a fever, and in some cases, encephalitis, which can lead to death . A vaccine to provide protection from yellow fever exists, and measures to prevent mosquito bites include insecticides such as DDT , mosquito traps , insect repellents , mosquito nets , and pest control using genetically modified insects . In Polynesia , the species Aedes polynesiensis is responsible for the transmission of human lymphatic filariasis . Aedes can be detected and monitored by ovitraps .The genome of the yellow fever mosquito ( Aedes aegypti ) was sequenced by the Broad Institute and the Institute for Genomic Research . The initial assembly was released in August 2005; a draft sequence of the genome and preliminary analysis was published in June 2007. The annotated genome is available at VectorBase . An updated and improved version of the Aedes aegypti genome was released in 2018.

Wiki

Chikungunya

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

MMR vaccine

None The MMR vaccine is a vaccine against measles , mumps , and rubella (German measles), abbreviated as MMR . The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, with at least four weeks between the doses. After two doses, 97% of people are protected against measles, 88% against mumps, and at least 97% against rubella. The vaccine is also recommended for those who do not have evidence of immunity , those with well-controlled HIV/AIDS , and within 72 hours of exposure to measles among those who are incompletely immunized. It is given by injection . The MMR vaccine is widely used around the world. Worldwide over 500 million doses were administered between 1999 and 2004, and 575 million doses have been administered since the vaccine's introduction worldwide. Measles resulted in 2.6 million deaths per year before immunization became common. This has decreased to 122,000 deaths per year as of 2012 , [ update ] mostly in low-income countries. Through vaccination, as of 2018 [ update ] , rates of measles in North and South America are very low. Rates of disease have been seen to increase in populations that go unvaccinated. Between 2000 and 2018, vaccination decreased measles deaths by 73%. Side effects of immunization are generally mild and resolve without any specific treatment. These may include fever , as well as pain or redness at the injection site. Severe allergic reactions occur in about one in a million people. Because it contains live viruses, the MMR vaccine is not recommended during pregnancy but may be given while breastfeeding . The vaccine is safe to give at the same time as other vaccines. Being recently immunized does not increase the risk of passing measles, mumps, or rubella on to others. There is no evidence of an association between MMR immunisation and autistic spectrum disorders . The MMR vaccine is a mixture of live weakened viruses of the three diseases. The MMR vaccine was developed by Maurice Hilleman . It was licensed for use in USA by Merck in 1971. Stand-alone measles , mumps , and rubella vaccines had been previously licensed in 1963, 1967, and 1969, respectively. Recommendations for a second dose were introduced in 1989. The MMRV vaccine , which also covers chickenpox , may be used instead. An MR vaccine , without coverage for mumps, is also occasionally used. Cochrane concluded that the "Existing evidence on the safety and effectiveness of MMR and MMRV vaccine supports current policies of mass immunisation aimed at global measles eradication in order to reduce morbidity and mortality associated with measles mumps rubella and varicella." The combined MMR vaccine induces immunity less painfully than three separate injections at the same time, and sooner and more efficiently than three injections given on different dates. Public Health England reports that providing a single combined vaccine as of 1988, rather than giving the option to have them also done separately, increased uptake of the vaccine. Before the widespread use of a vaccine against measles , rates of disease were so high that infection was felt to be "as inevitable as death and taxes." Reported cases of measles in the United States fell from hundreds of thousands to tens of thousands per year following introduction of the vaccine in 1963. Increasing uptake of the vaccine following outbreaks in 1971, and 1977, brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. Fewer than 200 cases have been reported in the US each year between 1997 and 2013, and the disease is no longer considered endemic there. The benefit of measles vaccination in preventing illness, disability, and death has been well documented. The first 20 years of licensed measles vaccination in the US prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability , and 5,200 deaths. During 1999–2004, a strategy led by the World Health Organization and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. Between 2000 and 2018, measles vaccination resulted in a 73% decrease in deaths from the disease. Measles is common in many areas of the world. Although it was declared eliminated from the US in 2000, high rates of vaccination and good communication with people who refuse vaccination are needed to prevent outbreaks and sustain the elimination of measles in the US. Of the 66 cases of measles reported in the US in 2005, slightly over half were attributable to one unvaccinated individual who acquired measles during a visit to Romania . This individual returned to a community with many unvaccinated children. The resulting outbreak infected 34 people, mostly children and virtually all unvaccinated; 9% were hospitalized, and the cost of containing the outbreak was estimated at $167,685. A major epidemic was averted due to high rates of vaccination in the surrounding communities. In 2017, an outbreak of measles occurred among the Somali-American community in Minnesota, where MMR vaccination rates had declined due to the misconception that the vaccine could cause autism. The US Centers for Disease Control and Prevention recorded 65 affected children in the outbreak by April 2017. Rubella , also known as German measles, was also very common before widespread vaccination. The major risk of rubella is during pregnancy when the baby may contract congenital rubella , which can cause significant congenital defects. Mumps is another viral disease that was once very common, especially during childhood. If mumps is acquired by a male who is past puberty , a possible complication is bilateral orchitis , which can in some cases lead to sterility . The MMR vaccine is administered by a subcutaneous injection , the first dose typically at twelve months of age. The second dose may be given as early as one month after the first dose. The second dose is a dose to produce immunity in the small number of persons (2–5%) who fail to develop measles immunity after the first dose. In the US it is done before entry to kindergarten because that is a convenient time. Areas where measles is common typically recommend the first dose at nine months of age and the second dose at fifteen months of age. Before the widespread use of a vaccine against measles , rates of disease were so high that infection was felt to be "as inevitable as death and taxes." Reported cases of measles in the United States fell from hundreds of thousands to tens of thousands per year following introduction of the vaccine in 1963. Increasing uptake of the vaccine following outbreaks in 1971, and 1977, brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. Fewer than 200 cases have been reported in the US each year between 1997 and 2013, and the disease is no longer considered endemic there. The benefit of measles vaccination in preventing illness, disability, and death has been well documented. The first 20 years of licensed measles vaccination in the US prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability , and 5,200 deaths. During 1999–2004, a strategy led by the World Health Organization and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. Between 2000 and 2018, measles vaccination resulted in a 73% decrease in deaths from the disease. Measles is common in many areas of the world. Although it was declared eliminated from the US in 2000, high rates of vaccination and good communication with people who refuse vaccination are needed to prevent outbreaks and sustain the elimination of measles in the US. Of the 66 cases of measles reported in the US in 2005, slightly over half were attributable to one unvaccinated individual who acquired measles during a visit to Romania . This individual returned to a community with many unvaccinated children. The resulting outbreak infected 34 people, mostly children and virtually all unvaccinated; 9% were hospitalized, and the cost of containing the outbreak was estimated at $167,685. A major epidemic was averted due to high rates of vaccination in the surrounding communities. In 2017, an outbreak of measles occurred among the Somali-American community in Minnesota, where MMR vaccination rates had declined due to the misconception that the vaccine could cause autism. The US Centers for Disease Control and Prevention recorded 65 affected children in the outbreak by April 2017. Rubella , also known as German measles, was also very common before widespread vaccination. The major risk of rubella is during pregnancy when the baby may contract congenital rubella , which can cause significant congenital defects. Mumps is another viral disease that was once very common, especially during childhood. If mumps is acquired by a male who is past puberty , a possible complication is bilateral orchitis , which can in some cases lead to sterility . The MMR vaccine is administered by a subcutaneous injection , the first dose typically at twelve months of age. The second dose may be given as early as one month after the first dose. The second dose is a dose to produce immunity in the small number of persons (2–5%) who fail to develop measles immunity after the first dose. In the US it is done before entry to kindergarten because that is a convenient time. Areas where measles is common typically recommend the first dose at nine months of age and the second dose at fifteen months of age. Adverse reactions , rarely serious, may occur from each component of the MMR vaccine. Ten percent of children develop fever, malaise , and a rash 5–21 days after the first vaccination; and 3% develop joint pain lasting 18 days on average. Older women appear to be more at risk of joint pain, acute arthritis , and even (rarely) chronic arthritis. Anaphylaxis is an extremely rare but serious allergic reaction to the vaccine. One cause can be egg allergy . In 2014, the FDA approved two additional possible adverse events on the vaccination label: acute disseminated encephalomyelitis (ADEM), and transverse myelitis , with permission to also add "difficulty walking" to the package inserts. A 2012 IOM report found that the measles component of the MMR vaccine can cause measles inclusion body encephalitis in immunocompromised individuals. This report also rejected any connection between the MMR vaccine and autism . Some versions of the vaccine contain the antibiotic neomycin and therefore should not be used in people allergic to this antibiotic. The number of reports on neurological disorders is very small, other than evidence for an association between a form of the MMR vaccine containing the Urabe mumps strain and rare adverse events of aseptic meningitis , a form of viral meningitis. The UK National Health Service stopped using the Urabe mumps strain in the early 1990s due to cases of transient mild viral meningitis, and switched to a form using the Jeryl Lynn mumps strain instead. The Urabe strain remains in use in a number of countries; MMR with the Urabe strain is much cheaper to manufacture than with the Jeryl Lynn strain, and a strain with higher efficacy along with a somewhat higher rate of mild side effects may still have the advantage of reduced incidence of overall adverse events. A Cochrane review found that, compared with placebo, MMR vaccine was associated with fewer upper respiratory tract infections, more irritability, and a similar number of other adverse effects. Naturally acquired measles often occurs with immune thrombocytopenic purpura (ITP, a purpuric rash and an increased tendency to bleed that resolves within two months in children), occurring in 1 to 20,000 cases. Approximately 1 in 40,000 children are thought to acquire ITP in the six weeks following an MMR vaccination. ITP below the age of six years is generally a mild disease, rarely having long-term consequences. In 1998 Andrew Wakefield et al. published a fraudulent paper about twelve children, reportedly with bowel symptoms and autism or other disorders acquired soon after administration of MMR vaccine, while supporting a competing vaccine. In 2010, Wakefield's research was found by the General Medical Council to have been "dishonest", and The Lancet fully retracted the paper. Three months following The Lancet's retraction, Wakefield was struck off the UK medical register , with a statement identifying deliberate falsification in the research published in The Lancet , and was barred from practising medicine in the UK. The research was declared fraudulent in 2011 by the British Medical Journal . Since Wakefield's publication, multiple peer-reviewed studies have failed to show any association between the vaccine and autism. The US Centers for Disease Control and Prevention , the Institute of Medicine of the US National Academy of Sciences , the UK National Health Service and the Cochrane Library review have all concluded that there is no evidence of a link. Administering the vaccines in three separate doses does not reduce the chance of adverse effects, and it increases the opportunity for infection by the two diseases not immunized against first. Health experts have criticized media reporting of the MMR-autism controversy for triggering a decline in vaccination rates. Before publication of Wakefield's article, the inoculation rate for MMR in the UK was 92%; after publication, the rate dropped to below 80%. In 1998, there were 56 measles cases in the UK; by 2008, there were 1348 cases, with two confirmed deaths. In Japan, the MMR triplet is not used. Immunity is achieved by a combination vaccine for measles and rubella, followed up later with a mumps only vaccine. This has had no effect on autism rates in the country, further disproving the MMR autism hypothesis. In 1998 Andrew Wakefield et al. published a fraudulent paper about twelve children, reportedly with bowel symptoms and autism or other disorders acquired soon after administration of MMR vaccine, while supporting a competing vaccine. In 2010, Wakefield's research was found by the General Medical Council to have been "dishonest", and The Lancet fully retracted the paper. Three months following The Lancet's retraction, Wakefield was struck off the UK medical register , with a statement identifying deliberate falsification in the research published in The Lancet , and was barred from practising medicine in the UK. The research was declared fraudulent in 2011 by the British Medical Journal . Since Wakefield's publication, multiple peer-reviewed studies have failed to show any association between the vaccine and autism. The US Centers for Disease Control and Prevention , the Institute of Medicine of the US National Academy of Sciences , the UK National Health Service and the Cochrane Library review have all concluded that there is no evidence of a link. Administering the vaccines in three separate doses does not reduce the chance of adverse effects, and it increases the opportunity for infection by the two diseases not immunized against first. Health experts have criticized media reporting of the MMR-autism controversy for triggering a decline in vaccination rates. Before publication of Wakefield's article, the inoculation rate for MMR in the UK was 92%; after publication, the rate dropped to below 80%. In 1998, there were 56 measles cases in the UK; by 2008, there were 1348 cases, with two confirmed deaths. In Japan, the MMR triplet is not used. Immunity is achieved by a combination vaccine for measles and rubella, followed up later with a mumps only vaccine. This has had no effect on autism rates in the country, further disproving the MMR autism hypothesis. The component viral strains of MMR vaccine were developed by propagation in animal and human cells as all viruses require a living host cell to replicate. [ citation needed ] For example, in the case of mumps and measles viruses, the virus strains were grown in embryonated chicken eggs. This produced strains of virus which were adapted for chicken cells and less well-suited for human cells. These strains are therefore called attenuated strains . They are sometimes referred to as neuroattenuated because these strains are less virulent to human neurons than the wild strains. The Rubella component, Meruvax, was developed in 1967, through propagation using the human embryonic lung cell line WI-38 (named for the Wistar Institute ) that was derived six years earlier in 1961. The term "MPR vaccine" is also used to refer to this vaccine, whereas "P" refer to parotitis which is caused by mumps. Merck MMR II is supplied freeze-dried ( lyophilized ) and contains live viruses. Before injection it is reconstituted with the solvent provided. According to a review published in 2018, the GlaxoSmithKline (GSK) MMR vaccine known as Pluserix "contains the Schwarz measles virus, the Jeryl Lynn–like mumps strain, and RA27/3 rubella virus". Pluserix was introduced in Hungary in 1999. Enders' Edmonston strain has been used since 1999 in Hungary in Merck MMR II product. GSK Priorix vaccine, which uses attenuated Schwarz Measles, was introduced in Hungary in 2003. The MMRV vaccine , a combined measles, mumps, rubella and varicella (chickenpox) vaccine, has been proposed as a replacement for the MMR vaccine to simplify administration of the vaccines. Preliminary data indicate a rate of febrile seizures of 9 per 10,000 vaccinations with MMRV, as opposed to 4 per 10,000 for separate MMR and varicella shots; US health officials therefore do not express a preference for use of MMRV vaccine over separate injections. In a 2012 study pediatricians and family doctors were sent a survey to gauge their awareness of the increased risk of febrile seizures (fever fits) in the MMRV. 74% of family doctors and 29% of pediatricians were unaware of the increased risk of febrile seizures. After reading an informational statement only 7% of family doctors and 20% of pediatricians would recommend the MMRV for a healthy 12- to 15-month-old child. The factor that was reported as the "most important" deciding factor in recommending the MMRV over the MMR+V was ACIP / AAFP / AAP recommendations (pediatricians, 77%; family physicians, 73%).This is a vaccine that covers measles and rubella but not mumps. As of 2014, it was used in a "few (unidentified) countries". Some brands of the vaccine use gelatin , derived from pigs , as a stabilizer . This has caused reduced take-up among some communities, despite the fact that alternative vaccines without pig derivatives are approved and available. Some brands of the vaccine use gelatin , derived from pigs , as a stabilizer . This has caused reduced take-up among some communities, despite the fact that alternative vaccines without pig derivatives are approved and available.

Wiki

Chikungunya

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

Japanese encephalitis

Japanese encephalitis ( JE ) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs . In these cases, symptoms may include headache, vomiting, fever, confusion and seizures . This occurs about 5 to 15 days after infection. JEV is generally spread by mosquitoes , specifically those of the Culex type. Pigs and wild birds serve as a reservoir for the virus. The disease occurs mostly outside of cities. Diagnosis is based on blood or cerebrospinal fluid testing. Prevention is generally achieved with the Japanese encephalitis vaccine , which is both safe and effective. Other measures include avoiding mosquito bites. Once infected, there is no specific treatment, with care being supportive . This is generally carried out in a hospital. Permanent problems occur in up to half of people who recover from JE. The disease primarily occurs in East and Southeast Asia as well as the Western Pacific . About 3 billion people live in areas where the disease occurs. About 68,000 symptomatic cases occur a year, with about 17,000 deaths. Often, cases occur in outbreaks . The disease was first described in Japan in 1871 . The Japanese encephalitis virus (JEV) has an incubation period of 2 to 26 days. The vast majority of infections are asymptomatic : only 1 in 250 infections develop into encephalitis. Severe rigors may mark the onset of this disease in humans. Fever, headache and malaise are other non-specific symptoms of this disease which may last for a period of between 1 and 6 days. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia , hemiparesis , convulsions and a raised body temperature between 38–41 °C (100.4–105.8 °F) . The mortality rate of the disease is around 25% and is generally higher in children under five, the immuno-suppressed and the elderly. Transplacental spread has been noted. Neurological disorders develop in 40% of those who survive with lifelong neurological defects such as deafness, emotional lability and hemiparesis occurring in those who had central nervous system involvement. Increased microglial activation following Japanese encephalitis infection has been found to influence the outcome of viral pathogenesis. Microglia are the resident immune cells of the central nervous system (CNS) and have a critical role in host defense against invading microorganisms. Activated microglia secrete cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α) , which can cause toxic effects in the brain. Additionally, other soluble factors such as neurotoxins , excitatory neurotransmitters , prostaglandin , reactive oxygen , and nitrogen species are secreted by activated microglia. [ citation needed ] In a murine model of JE, it was found that in the hippocampus and the striatum , the number of activated microglia was more than anywhere else in the brain, closely followed by that in the thalamus . In the cortex, the number of activated microglia was significantly less when compared to other regions of the mouse brain . An overall induction of differential expression of proinflammatory cytokines and chemokines from different brain regions during a progressive Japanese encephalitis infection was also observed. [ citation needed ] Although the net effect of the proinflammatory mediators is to kill infectious organisms and infected cells as well as to stimulate the production of molecules that amplify the mounting response to damage, it is also evident that in a nonregenerating organ such as the brain, a dysregulated innate immune response would be deleterious. In JE the tight regulation of microglial activation appears to be disturbed, resulting in an autotoxic loop of microglial activation that possibly leads to bystander neuronal damage. In animals, key signs include infertility and abortion in pigs, neurological disease in horses, and systemic signs including fever, lethargy and anorexia. It is a disease caused by the mosquito -borne Japanese encephalitis virus (JEV). JEV is a virus from the family Flaviviridae , part of the Japanese encephalitis serocomplex of 9 genetically and antigenically related viruses, some which are particularly severe in horses , and four known to infect humans including West Nile virus . The enveloped virus is closely related to the West Nile virus and the St. Louis encephalitis virus. The positive sense single-stranded RNA genome is packaged in the capsid which is formed by the capsid protein. The outer envelope is formed by envelope protein and is the protective antigen. It aids in entry of the virus into the cell. The genome also encodes several nonstructural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as a secretory form also. NS3 is a putative helicase , and NS5 is the viral polymerase . It has been noted that Japanese encephalitis infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins. Based on the envelope gene, there are five genotypes (I–V). The Muar strain, isolated from a patient in Malaya in 1952, is the prototype strain of genotype V. Genotype V is the earliest recognized ancestral strain. The first clinical reports date from 1870, but the virus appears to have evolved in the mid-16th century. Over sixty complete genomes of this virus had been sequenced by 2010. [ citation needed ]JEV is a virus from the family Flaviviridae , part of the Japanese encephalitis serocomplex of 9 genetically and antigenically related viruses, some which are particularly severe in horses , and four known to infect humans including West Nile virus . The enveloped virus is closely related to the West Nile virus and the St. Louis encephalitis virus. The positive sense single-stranded RNA genome is packaged in the capsid which is formed by the capsid protein. The outer envelope is formed by envelope protein and is the protective antigen. It aids in entry of the virus into the cell. The genome also encodes several nonstructural proteins (NS1, NS2a, NS2b, NS3, N4a, NS4b, NS5). NS1 is produced as a secretory form also. NS3 is a putative helicase , and NS5 is the viral polymerase . It has been noted that Japanese encephalitis infects the lumen of the endoplasmic reticulum (ER) and rapidly accumulates substantial amounts of viral proteins. Based on the envelope gene, there are five genotypes (I–V). The Muar strain, isolated from a patient in Malaya in 1952, is the prototype strain of genotype V. Genotype V is the earliest recognized ancestral strain. The first clinical reports date from 1870, but the virus appears to have evolved in the mid-16th century. Over sixty complete genomes of this virus had been sequenced by 2010. [ citation needed ]Japanese encephalitis is diagnosed by commercially available tests detecting JE virus-specific IgM antibodies in serum and/or cerebrospinal fluid , for example by IgM capture ELISA . JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and persist for 30 to 90 days, but longer persistence has been documented. Therefore, positive IgM antibodies occasionally may reflect a past infection or vaccination. Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample. For patients with JE virus IgM antibodies, confirmatory neutralizing antibody testing should be performed. Confirmatory testing in the US is available only at the CDC and a few specialized reference laboratories. In fatal cases, nucleic acid amplification and virus culture of autopsy tissues can be useful. Viral antigen can be shown in tissues by indirect fluorescent antibody staining . Infection with Japanese encephalitis confers lifelong immunity . There are currently three vaccines available: SA14-14-2, IXIARO (IC51, also marketed in Australia, New Zealand as JESPECT and India as JEEV ) and ChimeriVax-JE (marketed as IMOJEV). All current vaccines are based on the genotype III virus. [ citation needed ] A formalin -inactivated mouse-brain-derived vaccine was first produced in Japan in the 1930s and was validated for use in Taiwan in the 1960s and in Thailand in the 1980s. The widespread use of vaccine and urbanization has led to control of the disease in Japan and Singapore. The high cost of this vaccine, which is grown in live mice, means that poorer countries have not been able to afford to give it as part of a routine immunization program. The most common adverse effects are redness and pain at the injection site. Uncommonly, an urticarial reaction can develop about four days after injection. Vaccines produced from mouse brain have a risk of autoimmune neurological complications of around 1 per million vaccinations. However where the vaccine is not produced in mouse brains but in vitro using cell culture there are few adverse effects compared to placebo , the main side effects being headache and myalgia . The neutralizing antibody persists in the circulation for at least two to three years, and perhaps longer. The total duration of protection is unknown, but because there is no firm evidence for protection beyond three years, boosters are recommended every three years for people who remain at risk. Furthermore, there are no data available regarding the interchangeability of other JE vaccines and IXIARO. [ citation needed ]There is no specific treatment for Japanese encephalitis and treatment is supportive, with assistance given for feeding , breathing or seizure control as required. Raised intracranial pressure may be managed with mannitol . There is no transmission from person to person and therefore patients do not need to be isolated. [ citation needed ] A breakthrough in the field of Japanese encephalitis therapeutics is the identification of macrophage receptor involvement in the disease severity. A recent report of an Indian group demonstrates the involvement of monocyte and macrophage receptor CLEC5A in severe inflammatory response in Japanese encephalitis infection of the brain. This transcriptomic study provides a hypothesis of neuroinflammation and a new lead in development of appropriate therapies for Japanese encephalitis. The effectiveness of intravenous immunoglobulin for the management of encephalitis is unclear due to a lack of evidence. Intravenous immunoglobulin for Japanese encephalitis appeared to have no benefit. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia , with up to 70,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depend on the population and age. Rare outbreaks in U.S. territories in the Western Pacific have also occurred. Residents of rural areas in endemic locations are at highest risk; Japanese encephalitis does not usually occur in urban areas. [ citation needed ] Countries which have had major epidemics in the past, but which have controlled the disease primarily by vaccination, include China , South Korea , Singapore , Japan , Taiwan and Thailand . Other countries that still have periodic epidemics include Vietnam , Cambodia , Myanmar , India , Nepal , and Malaysia . Japanese encephalitis has been reported in the Torres Strait Islands , and two fatal cases were reported in mainland northern Australia in 1998. There were reported cases in Kachin State , Myanmar in 2013. There were 116 deaths reported in Odisha's Malkangiri district of India in 2016. [ citation needed ] In 2022, the notable increase in distribution of the virus in Australia due to climate change became a concern to health officials as the population has limited immunity to the disease and the presence of large numbers of farmed and feral pigs could act as reservoirs for the virus. In February 2022, Japanese encephalitis was detected and confirmed in piggeries in Victoria, Queensland and New South Wales. On 4 March, cases were detected in South Australia. By October 2022, the outbreak in eastern mainland Australia had caused 42 symptomatic human cases of the disease, resulting in seven deaths. Humans, cattle, and horses are dead-end hosts as the disease manifests as fatal encephalitis. Pigs act as an amplifying host and have a very important role in the epidemiology of the disease. Infection in swine is asymptomatic, except in pregnant sows, when abortion and fetal abnormalities are common sequelae. The most important vector is Culex tritaeniorhynchus , which feeds on cattle in preference to humans. The natural hosts of the Japanese encephalitis virus are birds, not humans, and many believe the virus will therefore never be eliminated. In November 2011, the Japanese encephalitis virus was reported in Culex bitaeniorhynchus in South Korea . Recently, whole genome microarray research of neurons infected with the Japanese encephalitis virus has shown that neurons play an important role in their own defense against Japanese encephalitis infection. Although this challenges the long-held belief that neurons are immunologically quiescent, an improved understanding of the proinflammatory effects responsible for immune-mediated control of viral infection and neuronal injury during Japanese encephalitis infection is an essential step for developing strategies for limiting the severity of CNS disease. A number of drugs have been investigated to either reduce viral replication or provide neuroprotection in cell lines or studies upon mice. None are currently advocated in treating human patients.It is theorized that the virus may have originated from an ancestral virus in the mid-1500s in the Malay Archipelago region and evolved there into five different genotypes which spread across Asia. The mean evolutionary rate has been estimated to be 4.35 × 10 −4 (range: 3.49 × 10 −4 to 5.30 × 10 −4 ) nucleotide substitutions per site per year.

Wiki

Chikungunya

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

Malaria vaccine

EU : Rx-only Approved in Ghana, Nigeria none Malaria vaccines are vaccines that prevent malaria , a mosquito-borne infectious disease which annually affects an estimated 247 million people worldwide and causes 619,000 deaths. The first approved vaccine for malaria is RTS,S , known by the brand name Mosquirix. As of April 2023 [ update ] , the vaccine has been given to 1.5 million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%. Research continues with other malaria vaccines. The most effective malaria vaccine is the R21/Matrix-M, with a 77% efficacy rate shown in initial trials and significantly higher antibody levels than with the RTS,S vaccine. It is the first vaccine that meets the World Health Organization 's (WHO) goal of a malaria vaccine with at least 75% efficacy, and only the second malaria vaccine to be recommended by the WHO. In April 2023, Ghana 's Food and Drugs Authority approved the use of the R21 vaccine for use in children aged between five months and three years old. Following Ghana's decision, Nigeria provisionally approved the R21 vaccine. RTS,S/AS01 (brand name Mosquirix) is the first malaria vaccine approved for public use. It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%. RTS,S was developed by PATH Malaria Vaccine Initiative (MVI) and GlaxoSmithKline (GSK) with support from the Bill and Melinda Gates Foundation . It is a recombinant vaccine, consisting of the Plasmodium falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage. The CSP antigen causes the production of antibodies capable of preventing the invasion of hepatocytes and also elicits a cellular response enabling the destruction of infected hepatocytes. The CSP vaccine presented problems in the trial stage due to its poor immunogenicity . RTS,S attempted to avoid these by fusing the protein with a surface antigen from hepatitis B virus , creating a more potent and immunogenic vaccine. When tested in trials as an emulsion of oil in water and with the added adjuvants of monophosphoryl A and QS21 (SBAS2), the vaccine gave protective immunity to 7 out of 8 volunteers when challenged with P. falciparum. RTS,S was engineered using genes from the outer protein of P. falciparum malaria parasite and a portion of a hepatitis B virus plus a chemical adjuvant to boost the immune response. Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver. In November 2012, a Phase III trial of RTS,S found that it provided modest protection against both clinical and severe malaria in young infants. In October 2013, preliminary results of a phase III clinical trial indicated that RTS,S/AS01 reduced the number of cases among young children by almost 50 percent and among infants by around 25 percent. The study ended in 2014. The effects of a booster dose were positive, even though overall efficacy seems to wane with time. After four years, reductions were 36 percent for children who received three shots and a booster dose. Missing the booster dose reduced the efficacy against severe malaria to a negligible effect. The vaccine was shown to be less effective for infants. Three doses of vaccine plus a booster reduced the risk of clinical episodes by 26 percent over three years but offered no significant protection against severe malaria. In a bid to accommodate a larger group and guarantee a sustained availability for the general public, GSK applied for a marketing license with the European Medicines Agency (EMA) in July 2014. GSK treated the project as a non-profit initiative, with most funding coming from the Gates Foundation, a major contributor to malaria eradication. In July 2015, Mosquirix received a positive scientific opinion from the European Medicines Agency (EMA) on the proposal for the vaccine to be used to vaccinate children aged 6 weeks to 17 months outside the European Union. A pilot project for vaccination was launched on 23 April 2019 in Malawi , on 30 April 2019 in Ghana , and on 13 September 2019 in Kenya . In October 2021, the vaccine was endorsed by the World Health Organization for "broad use" in children, making it the first malaria vaccine to receive this recommendation. The vaccine was prequalified by WHO in July 2022. In August 2022, UNICEF awarded a contract to GSK to supply 18 million doses of the RTS,S vaccine over three years. More than 30 countries have areas with moderate to high malaria transmission where the vaccine is expected to be useful. As of April 2023 [ update ] , 1.5 million children in Ghana, Kenya and Malawi had received at least one injection of the vaccine, with more than 4.5 million doses of the vaccine administered through the countries' routine immunization programs. The next 9 countries to receive the vaccine over the next 2 years are Benin, Burkina Faso, Burundi, Cameroon, the Democratic Republic of the Congo, Liberia, Niger, Sierra Leone, and Uganda. The most effective malaria vaccine is R21/Matrix-M, with 77% efficacy shown in initial trials. It is the first vaccine that meets the World Health Organization's goal of a malaria vaccine with at least 75% efficacy. It was developed through a collaboration involving the Jenner Institute at the University of Oxford , the Kenya Medical Research Institute , the London School of Hygiene and Tropical Medicine , Novavax , and the Serum Institute of India . The trials took place at the Institut de Recherche en Sciences de la Santé in Nanoro , Burkina Faso with Halidou Tinto as the principal investigator. The R21 vaccine uses a circumsporozoite protein (CSP) antigen, at a higher proportion than the RTS,S vaccine. It uses the same HBsAg-linked recombinant structure, but contains no excess HBsAg. It includes the Matrix-M adjuvant that is also utilized in the Novavax COVID-19 vaccine . A phase II trial was reported in April 2021, with a vaccine efficacy of 77% and antibody levels significantly higher than with the RTS,S vaccine. A booster shot of R21/Matrix-M that is given 12 months after the primary three-dose regimen maintains a high efficacy against malaria, providing high protection against symptomatic malaria for at least 2 years. A phase III trial with 4,800 children across four African countries was reported in November 2022, demonstrating vaccine efficacy of 74% against a severe malaria episode. Further data from multiple studies is being collected. As of April 2023 [ update ] data from the phase III study had not been formally published, but late-stage data from the study was shared with regulatory authorities. Ghana's Food and Drugs Authority approved the use of the R21 vaccine in April 2023, for use in children aged between five months to three years old. The Serum Institute of India is preparing to produce between 100–200 million doses of the vaccine per year, and is constructing a vaccine factory in Accra, Ghana . Following Ghana's decision, Nigeria provisionally approved the R21 vaccine. In October 2023 the WHO endorsed the R21 vaccine against malaria, end of December 2023 it was added to the list of Prequalified Vaccines . RTS,S/AS01 (brand name Mosquirix) is the first malaria vaccine approved for public use. It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%. RTS,S was developed by PATH Malaria Vaccine Initiative (MVI) and GlaxoSmithKline (GSK) with support from the Bill and Melinda Gates Foundation . It is a recombinant vaccine, consisting of the Plasmodium falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage. The CSP antigen causes the production of antibodies capable of preventing the invasion of hepatocytes and also elicits a cellular response enabling the destruction of infected hepatocytes. The CSP vaccine presented problems in the trial stage due to its poor immunogenicity . RTS,S attempted to avoid these by fusing the protein with a surface antigen from hepatitis B virus , creating a more potent and immunogenic vaccine. When tested in trials as an emulsion of oil in water and with the added adjuvants of monophosphoryl A and QS21 (SBAS2), the vaccine gave protective immunity to 7 out of 8 volunteers when challenged with P. falciparum. RTS,S was engineered using genes from the outer protein of P. falciparum malaria parasite and a portion of a hepatitis B virus plus a chemical adjuvant to boost the immune response. Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver. In November 2012, a Phase III trial of RTS,S found that it provided modest protection against both clinical and severe malaria in young infants. In October 2013, preliminary results of a phase III clinical trial indicated that RTS,S/AS01 reduced the number of cases among young children by almost 50 percent and among infants by around 25 percent. The study ended in 2014. The effects of a booster dose were positive, even though overall efficacy seems to wane with time. After four years, reductions were 36 percent for children who received three shots and a booster dose. Missing the booster dose reduced the efficacy against severe malaria to a negligible effect. The vaccine was shown to be less effective for infants. Three doses of vaccine plus a booster reduced the risk of clinical episodes by 26 percent over three years but offered no significant protection against severe malaria. In a bid to accommodate a larger group and guarantee a sustained availability for the general public, GSK applied for a marketing license with the European Medicines Agency (EMA) in July 2014. GSK treated the project as a non-profit initiative, with most funding coming from the Gates Foundation, a major contributor to malaria eradication. In July 2015, Mosquirix received a positive scientific opinion from the European Medicines Agency (EMA) on the proposal for the vaccine to be used to vaccinate children aged 6 weeks to 17 months outside the European Union. A pilot project for vaccination was launched on 23 April 2019 in Malawi , on 30 April 2019 in Ghana , and on 13 September 2019 in Kenya . In October 2021, the vaccine was endorsed by the World Health Organization for "broad use" in children, making it the first malaria vaccine to receive this recommendation. The vaccine was prequalified by WHO in July 2022. In August 2022, UNICEF awarded a contract to GSK to supply 18 million doses of the RTS,S vaccine over three years. More than 30 countries have areas with moderate to high malaria transmission where the vaccine is expected to be useful. As of April 2023 [ update ] , 1.5 million children in Ghana, Kenya and Malawi had received at least one injection of the vaccine, with more than 4.5 million doses of the vaccine administered through the countries' routine immunization programs. The next 9 countries to receive the vaccine over the next 2 years are Benin, Burkina Faso, Burundi, Cameroon, the Democratic Republic of the Congo, Liberia, Niger, Sierra Leone, and Uganda. The most effective malaria vaccine is R21/Matrix-M, with 77% efficacy shown in initial trials. It is the first vaccine that meets the World Health Organization's goal of a malaria vaccine with at least 75% efficacy. It was developed through a collaboration involving the Jenner Institute at the University of Oxford , the Kenya Medical Research Institute , the London School of Hygiene and Tropical Medicine , Novavax , and the Serum Institute of India . The trials took place at the Institut de Recherche en Sciences de la Santé in Nanoro , Burkina Faso with Halidou Tinto as the principal investigator. The R21 vaccine uses a circumsporozoite protein (CSP) antigen, at a higher proportion than the RTS,S vaccine. It uses the same HBsAg-linked recombinant structure, but contains no excess HBsAg. It includes the Matrix-M adjuvant that is also utilized in the Novavax COVID-19 vaccine . A phase II trial was reported in April 2021, with a vaccine efficacy of 77% and antibody levels significantly higher than with the RTS,S vaccine. A booster shot of R21/Matrix-M that is given 12 months after the primary three-dose regimen maintains a high efficacy against malaria, providing high protection against symptomatic malaria for at least 2 years. A phase III trial with 4,800 children across four African countries was reported in November 2022, demonstrating vaccine efficacy of 74% against a severe malaria episode. Further data from multiple studies is being collected. As of April 2023 [ update ] data from the phase III study had not been formally published, but late-stage data from the study was shared with regulatory authorities. Ghana's Food and Drugs Authority approved the use of the R21 vaccine in April 2023, for use in children aged between five months to three years old. The Serum Institute of India is preparing to produce between 100–200 million doses of the vaccine per year, and is constructing a vaccine factory in Accra, Ghana . Following Ghana's decision, Nigeria provisionally approved the R21 vaccine. In October 2023 the WHO endorsed the R21 vaccine against malaria, end of December 2023 it was added to the list of Prequalified Vaccines . A completely effective vaccine is not available for malaria, although several vaccines are under development. Multiple vaccine candidates targeting the blood-stage of the parasite's lifecycle have been insufficient on their own. Several potential vaccines targeting the pre-erythrocytic stage are being developed, with RTS,S and R-21/Matrix-M the two approved options so far. In 2015, researchers used a repetitive antigen display technology to engineer a nanoparticle that displayed malaria specific B cell and T cell epitopes. The particle exhibited icosahedral symmetry and carried on its surface up to 60 copies of the RTS,S protein. The researchers claimed that the density of the protein was much higher than the 14% of the GSK vaccine. The PfSPZ vaccine is a candidate malaria vaccine developed by Sanaria using radiation-attenuated sporozoites to elicit an immune response. Clinical trials have been promising, with trials in Africa, Europe, and the US protecting over 80% of volunteers. It has been subject to some criticism regarding the ultimate feasibility of large-scale production and delivery in Africa, since it must be stored in liquid nitrogen . The PfSPZ vaccine candidate was granted fast track designation by the U.S. Food and Drug Administration in September 2016. In April 2019, a phase III trial in Bioko was announced, scheduled to start in early 2020. In 2015, researchers used a repetitive antigen display technology to engineer a nanoparticle that displayed malaria specific B cell and T cell epitopes. The particle exhibited icosahedral symmetry and carried on its surface up to 60 copies of the RTS,S protein. The researchers claimed that the density of the protein was much higher than the 14% of the GSK vaccine. The PfSPZ vaccine is a candidate malaria vaccine developed by Sanaria using radiation-attenuated sporozoites to elicit an immune response. Clinical trials have been promising, with trials in Africa, Europe, and the US protecting over 80% of volunteers. It has been subject to some criticism regarding the ultimate feasibility of large-scale production and delivery in Africa, since it must be stored in liquid nitrogen . The PfSPZ vaccine candidate was granted fast track designation by the U.S. Food and Drug Administration in September 2016. In April 2019, a phase III trial in Bioko was announced, scheduled to start in early 2020. The task of developing a preventive vaccine for malaria is a complex process. There are a number of considerations to be made concerning what strategy a potential vaccine should adopt. P. falciparum has demonstrated the capability, through the development of multiple drug-resistant parasites, for evolutionary change. The Plasmodium species has a very high rate of replication, much higher than that actually needed to ensure transmission in the parasite's lifecycle. [ citation needed ] This enables pharmaceutical treatments that are effective at reducing the reproduction rate, but not halting it, to exert a high selection pressure, thus favoring the development of resistance. The process of evolutionary change is one of the key considerations necessary when considering potential vaccine candidates. The development of resistance could cause a significant reduction in efficacy of any potential vaccine thus rendering useless a carefully developed and effective treatment. The parasite induces two main response types from the human immune system. These are anti-parasitic immunity and anti-toxic immunity. Taking this information into consideration an ideal vaccine candidate would attempt to generate a more substantial cell-mediated and antibody response on parasite presentation. This would have the benefit of increasing the rate of parasite clearance, thus reducing the experienced symptoms and providing a level of consistent future immunity against the parasite. By their very nature, protozoa are more complex organisms than bacteria and viruses, with more complicated structures and lifecycles. This presents problems in vaccine development but also increases the number of potential targets for a vaccine. These have been summarised into the lifecycle stage and the antibodies that could potentially elicit an immune response. [ citation needed ] The epidemiology of malaria varies enormously across the globe and has led to the belief that it may be necessary to adopt very different vaccine development strategies to target the different populations. A Type 1 vaccine is suggested for those exposed mostly to P. falciparum malaria in sub-Saharan Africa, with the primary objective to reduce the number of severe malaria cases and deaths in infants and children exposed to high transmission rates. The Type 2 vaccine could be thought of as a 'travelers' vaccine,' aiming to prevent all clinical symptoms in individuals with no previous exposure. This is another major public health problem, with malaria presenting as one of the most substantial threats to travelers' health. Problems with the available pharmaceutical therapies include costs, availability, adverse effects and contraindications, inconvenience, and compliance, many of which would be reduced or eliminated if an effective (greater than 85–90%) vaccine was developed. [ citation needed ] The lifecycle of the malaria parasite is particularly complex, presenting initial developmental problems. Despite the huge number of vaccines available, there are none that target parasitic infections. The distinct developmental stages involved in the lifecycle present numerous opportunities for targeting antigens, thus potentially eliciting an immune response. Theoretically, each developmental stage could have a vaccine developed specifically to target the parasite. Moreover, any vaccine produced would ideally have the ability to be of therapeutic value as well as preventing further transmission and is likely to consist of a combination of antigens from different phases of the parasite's development. More than 30 of these antigens are being researched [ when? ] by teams all over the world in the hope of identifying a combination that can elicit immunity in the inoculated individual. Some of the approaches involve surface expression of the antigen, inhibitory effects of specific antibodies on the lifecycle and the protective effects through immunization or passive transfer of antibodies between an immune and a non-immune host. The majority of research into malarial vaccines has focused on the Plasmodium falciparum strain due to the high mortality caused by the parasite and the ease of carrying out in vitro/in vivo studies. The earliest vaccines attempted to use the parasitic circumsporozoite protein (CSP). This is the most dominant surface antigen of the initial pre-erythrocytic phase. However, problems were encountered due to low efficacy, reactogenicity and low immunogenicity . [ citation needed ] Increasing the potential immunity generated against Plasmodia can be achieved by attempting to target multiple phases in the lifecycle. This is additionally beneficial in reducing the possibility of resistant parasites developing. The use of multiple-parasite antigens can therefore have a synergistic or additive effect. One of the most successful vaccine candidates in clinical trials consists of recombinant antigenic proteins to the circumsporozoite protein . P. falciparum has demonstrated the capability, through the development of multiple drug-resistant parasites, for evolutionary change. The Plasmodium species has a very high rate of replication, much higher than that actually needed to ensure transmission in the parasite's lifecycle. [ citation needed ] This enables pharmaceutical treatments that are effective at reducing the reproduction rate, but not halting it, to exert a high selection pressure, thus favoring the development of resistance. The process of evolutionary change is one of the key considerations necessary when considering potential vaccine candidates. The development of resistance could cause a significant reduction in efficacy of any potential vaccine thus rendering useless a carefully developed and effective treatment. The parasite induces two main response types from the human immune system. These are anti-parasitic immunity and anti-toxic immunity. Taking this information into consideration an ideal vaccine candidate would attempt to generate a more substantial cell-mediated and antibody response on parasite presentation. This would have the benefit of increasing the rate of parasite clearance, thus reducing the experienced symptoms and providing a level of consistent future immunity against the parasite.By their very nature, protozoa are more complex organisms than bacteria and viruses, with more complicated structures and lifecycles. This presents problems in vaccine development but also increases the number of potential targets for a vaccine. These have been summarised into the lifecycle stage and the antibodies that could potentially elicit an immune response. [ citation needed ] The epidemiology of malaria varies enormously across the globe and has led to the belief that it may be necessary to adopt very different vaccine development strategies to target the different populations. A Type 1 vaccine is suggested for those exposed mostly to P. falciparum malaria in sub-Saharan Africa, with the primary objective to reduce the number of severe malaria cases and deaths in infants and children exposed to high transmission rates. The Type 2 vaccine could be thought of as a 'travelers' vaccine,' aiming to prevent all clinical symptoms in individuals with no previous exposure. This is another major public health problem, with malaria presenting as one of the most substantial threats to travelers' health. Problems with the available pharmaceutical therapies include costs, availability, adverse effects and contraindications, inconvenience, and compliance, many of which would be reduced or eliminated if an effective (greater than 85–90%) vaccine was developed. [ citation needed ] The lifecycle of the malaria parasite is particularly complex, presenting initial developmental problems. Despite the huge number of vaccines available, there are none that target parasitic infections. The distinct developmental stages involved in the lifecycle present numerous opportunities for targeting antigens, thus potentially eliciting an immune response. Theoretically, each developmental stage could have a vaccine developed specifically to target the parasite. Moreover, any vaccine produced would ideally have the ability to be of therapeutic value as well as preventing further transmission and is likely to consist of a combination of antigens from different phases of the parasite's development. More than 30 of these antigens are being researched [ when? ] by teams all over the world in the hope of identifying a combination that can elicit immunity in the inoculated individual. Some of the approaches involve surface expression of the antigen, inhibitory effects of specific antibodies on the lifecycle and the protective effects through immunization or passive transfer of antibodies between an immune and a non-immune host. The majority of research into malarial vaccines has focused on the Plasmodium falciparum strain due to the high mortality caused by the parasite and the ease of carrying out in vitro/in vivo studies. The earliest vaccines attempted to use the parasitic circumsporozoite protein (CSP). This is the most dominant surface antigen of the initial pre-erythrocytic phase. However, problems were encountered due to low efficacy, reactogenicity and low immunogenicity . [ citation needed ]Increasing the potential immunity generated against Plasmodia can be achieved by attempting to target multiple phases in the lifecycle. This is additionally beneficial in reducing the possibility of resistant parasites developing. The use of multiple-parasite antigens can therefore have a synergistic or additive effect. One of the most successful vaccine candidates in clinical trials consists of recombinant antigenic proteins to the circumsporozoite protein . Individuals who are exposed to the parasite in endemic countries develop acquired immunity against disease and death. Such immunity does not, however prevent malarial infection; immune individuals often harbour asymptomatic parasites in their blood. This does, however, imply that it is possible to create an immune response that protects against the harmful effects of the parasite. Research shows that if immunoglobulin is taken from immune adults, purified, and then given to individuals who have no protective immunity, some protection can be gained. In 1967, it was reported that a level of immunity to the Plasmodium berghei parasite could be given to mice by exposing them to sporozoites that had been irradiated by x-rays. Subsequent human studies in the 1970s showed that humans could be immunized against Plasmodium vivax and Plasmodium falciparum by exposing them to the bites of significant numbers of irradiated mosquitos. From 1989 to 1999, eleven volunteers recruited from the United States Public Health Service , United States Army , and United States Navy were immunized against Plasmodium falciparum by the bites of 1001–2927 mosquitoes that had been irradiated with 15,000 rads of gamma rays from a Co-60 or Cs-137 source. This level of radiation is sufficient to attenuate the malaria parasites so that, while they can still enter hepatic cells , they cannot develop into schizonts nor infect red blood cells . Over a span of 42 weeks, 24 of 26 tests on the volunteers showed that they were protected from malaria. In 1967, it was reported that a level of immunity to the Plasmodium berghei parasite could be given to mice by exposing them to sporozoites that had been irradiated by x-rays. Subsequent human studies in the 1970s showed that humans could be immunized against Plasmodium vivax and Plasmodium falciparum by exposing them to the bites of significant numbers of irradiated mosquitos. From 1989 to 1999, eleven volunteers recruited from the United States Public Health Service , United States Army , and United States Navy were immunized against Plasmodium falciparum by the bites of 1001–2927 mosquitoes that had been irradiated with 15,000 rads of gamma rays from a Co-60 or Cs-137 source. This level of radiation is sufficient to attenuate the malaria parasites so that, while they can still enter hepatic cells , they cannot develop into schizonts nor infect red blood cells . Over a span of 42 weeks, 24 of 26 tests on the volunteers showed that they were protected from malaria.

Wiki

Chikungunya

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

Molluscum contagiosum

Molluscum contagiosum ( MC ), sometimes called water warts , is a viral infection of the skin that results in small raised pink lesions with a dimple in the center. They may become itchy or sore, and occur singularly or in groups. Any area of the skin may be affected, with abdomen , legs, arms, neck, genital area , and face being the most common. Onset of the lesions is around seven weeks after infection. They usually go away within a year without scarring . The infection is caused by a poxvirus called the molluscum contagiosum virus (MCV). The virus is spread either by direct contact, including sexual activity , or via contaminated objects such as towels. The condition can also be spread to other areas of the body by the person themselves. Risk factors include a weak immune system , atopic dermatitis , and crowded living conditions. Following one infection, it is possible to get re-infected. Diagnosis is typically based on the appearance of the lesions. Prevention includes hand washing and not sharing personal items. While treatment is not necessary, some may wish to have the lesions removed for cosmetic reasons or to prevent spread. Removal may occur with freezing , laser therapy , or opening up the lesion and scraping the inside. Scraping the lesion can, however, result in scarring . The oral medication cimetidine , or podophyllotoxin cream applied to the skin, may also be used for treatment. Approximately 122 million people globally were affected by molluscum contagiosum as of 2010 (1.8% of the population). It is more common in children between the ages of one and ten years old. The condition has become more common in the United States since 1966. But having an infection is not a reason to keep a child out of school or daycare. Molluscum contagiosum lesions are flesh-colored, dome-shaped, and pearly in appearance. They are often 1–5 mm in diameter, with a dimpled center. Molluscum lesions are most commonly found on the face, arms, legs, torso, and armpits in children. Adults typically have molluscum lesions in the genital region and this is considered to be a sexually transmitted infection ; because of this, if genital lesions are found on a child, sexual abuse should be suspected. These lesions are generally not painful, but they may itch or become irritated. Picking or scratching the bumps may lead to a spread of the viral infection responsible for molluscum contagiosum, an additional bacterial infection, and scarring. In some cases, eczema develops around the lesions. Individual molluscum lesions may go away on their own within two months and generally clear completely without treatment or scarring in six to twelve months. Mean durations for an outbreak are variously reported from eight to about 18 months, but durations are reported as widely as six months to five years, lasting longer in immunosuppressed individuals. As the name implies, molluscum contagiosum is extremely contagious. Transmission of the molluscum contagiosum virus can occur many different ways including direct skin contact (e.g., contact sports or sexual activity), contact with an infected surface ( fomite ), or autoinoculation (self-infection) by scratching or picking molluscum lesions and then touching other parts of the skin not previously affected by the virus. Children are particularly susceptible to autoinoculation and may have widespread clusters of lesions. The viral infection is limited to a localized area on the topmost layer of the superficial layer of the skin . Once the virus-containing head of the lesion has been destroyed, the infection is gone. The central waxy core contains the virus. [ citation needed ]Diagnosis is made on the appearance; the virus cannot routinely be cultured. The diagnosis can be confirmed by excisional biopsy . [ citation needed ] Histologically, molluscum contagiosum is characterized by molluscum bodies (also known as Henderson-Patterson bodies) in the epidermis , above the stratum basale , which consist of cells with abundant large granular eosinophilic cytoplasmic inclusion bodies (accumulated virions) and a small nucleus that has been pushed to the periphery. Because molluscum contagiosum usually resolves without treatment and treatment options can cause discomfort to children, initial recommendations are often to simply wait for the lesions to resolve on their own. Of the treatments available, a meta-analysis of randomized controlled trials suggested that there is no difference between treatments in short term improvement, and no single treatment is significantly better than natural resolution of the condition. Bumps located in the genital area may be treated in an effort to prevent them from spreading. When treatment has resulted in the elimination of all bumps, the infection has been effectively cured and will not reappear unless the person is reinfected. For mild cases, over-the-counter topical medication, such as potassium hydroxide may provide a modest benefit. There is limited evidence for other topical agents including salicylic acid , benzoyl peroxide , and tretinoin , but none of these agents are recommended above the others to shorten infection duration. Studies have found cantharidin to be an effective and safe treatment for removing molluscum contagiosum. This medication is usually well tolerated though mild side effects such as pain or blistering are common. There is no high-quality evidence for cimetidine . However, oral cimetidine has been used as an alternative treatment for the pediatric population as it is generally well tolerated and less invasive. Berdazimer sodium , sold under the brand name Zelsuvmi, is a medication used for the treatment for molluscum contagiosum. Berdazimer sodium is a nitric oxide releasing agent. It is a polymer formed from sodium 1-hydroxy-3-methyl-3-(3-(trimethoxysilyl)propyl)-1-triazene-2-oxide and tetraethyl silicate . Imiquimod is a form of immunotherapy initially proposed as a treatment for molluscum based on promising results in small case series and clinical trials. However, two large randomized controlled trials , specifically requested by the U.S. Food and Drug Administration under the Best Pharmaceuticals for Children Act both demonstrated that imiquimod cream applied three times per week was no more effective than placebo cream for treating molluscum after 18 weeks of treatment in a total of 702 children aged 2–12 years. In 2007, results from those trials—which remain unpublished—were incorporated into FDA-approved prescribing information for imiquimod, which states: "Limitations of Use: Efficacy was not demonstrated for molluscum contagiosum in children aged 2–12." In 2007, the FDA also updated imiquimod's label concerning safety issues raised in the two large trials and an FDA-requested pharmacokinetic study (the latter of which was published). The updated safety label reads as follows: Surgical treatments include cryosurgery , in which liquid nitrogen is used to freeze and destroy lesions , as well as scraping them off with a curette . Application of liquid nitrogen may cause burning or stinging at the treated site, which may persist for a few minutes after the treatment. With liquid nitrogen, a blister may form at the treatment site, but it will slough off in two to four weeks. Cryosurgery and curette scraping can be painful procedures and can result in residual scarring. A 2014 systematic review of case reports and case series concluded that the limited available data suggest pulsed dye laser therapy is a safe and effective treatment for molluscum contagiosum and is generally well tolerated by children. Side effects seen with pulsed dye laser therapy included mild temporary pain at the site of therapy, bruising (lasting up to 2–3 weeks), and temporary discoloration of the treated skin (as long as 1–6 months). No cases of permanent scarring have been reported. As of 2009, however, there is no evidence for genital lesions. For mild cases, over-the-counter topical medication, such as potassium hydroxide may provide a modest benefit. There is limited evidence for other topical agents including salicylic acid , benzoyl peroxide , and tretinoin , but none of these agents are recommended above the others to shorten infection duration. Studies have found cantharidin to be an effective and safe treatment for removing molluscum contagiosum. This medication is usually well tolerated though mild side effects such as pain or blistering are common. There is no high-quality evidence for cimetidine . However, oral cimetidine has been used as an alternative treatment for the pediatric population as it is generally well tolerated and less invasive. Berdazimer sodium , sold under the brand name Zelsuvmi, is a medication used for the treatment for molluscum contagiosum. Berdazimer sodium is a nitric oxide releasing agent. It is a polymer formed from sodium 1-hydroxy-3-methyl-3-(3-(trimethoxysilyl)propyl)-1-triazene-2-oxide and tetraethyl silicate . Imiquimod is a form of immunotherapy initially proposed as a treatment for molluscum based on promising results in small case series and clinical trials. However, two large randomized controlled trials , specifically requested by the U.S. Food and Drug Administration under the Best Pharmaceuticals for Children Act both demonstrated that imiquimod cream applied three times per week was no more effective than placebo cream for treating molluscum after 18 weeks of treatment in a total of 702 children aged 2–12 years. In 2007, results from those trials—which remain unpublished—were incorporated into FDA-approved prescribing information for imiquimod, which states: "Limitations of Use: Efficacy was not demonstrated for molluscum contagiosum in children aged 2–12." In 2007, the FDA also updated imiquimod's label concerning safety issues raised in the two large trials and an FDA-requested pharmacokinetic study (the latter of which was published). The updated safety label reads as follows: Berdazimer sodium , sold under the brand name Zelsuvmi, is a medication used for the treatment for molluscum contagiosum. Berdazimer sodium is a nitric oxide releasing agent. It is a polymer formed from sodium 1-hydroxy-3-methyl-3-(3-(trimethoxysilyl)propyl)-1-triazene-2-oxide and tetraethyl silicate . Imiquimod is a form of immunotherapy initially proposed as a treatment for molluscum based on promising results in small case series and clinical trials. However, two large randomized controlled trials , specifically requested by the U.S. Food and Drug Administration under the Best Pharmaceuticals for Children Act both demonstrated that imiquimod cream applied three times per week was no more effective than placebo cream for treating molluscum after 18 weeks of treatment in a total of 702 children aged 2–12 years. In 2007, results from those trials—which remain unpublished—were incorporated into FDA-approved prescribing information for imiquimod, which states: "Limitations of Use: Efficacy was not demonstrated for molluscum contagiosum in children aged 2–12." In 2007, the FDA also updated imiquimod's label concerning safety issues raised in the two large trials and an FDA-requested pharmacokinetic study (the latter of which was published). The updated safety label reads as follows:Surgical treatments include cryosurgery , in which liquid nitrogen is used to freeze and destroy lesions , as well as scraping them off with a curette . Application of liquid nitrogen may cause burning or stinging at the treated site, which may persist for a few minutes after the treatment. With liquid nitrogen, a blister may form at the treatment site, but it will slough off in two to four weeks. Cryosurgery and curette scraping can be painful procedures and can result in residual scarring. A 2014 systematic review of case reports and case series concluded that the limited available data suggest pulsed dye laser therapy is a safe and effective treatment for molluscum contagiosum and is generally well tolerated by children. Side effects seen with pulsed dye laser therapy included mild temporary pain at the site of therapy, bruising (lasting up to 2–3 weeks), and temporary discoloration of the treated skin (as long as 1–6 months). No cases of permanent scarring have been reported. As of 2009, however, there is no evidence for genital lesions. Most cases of molluscum contagiosum will clear up naturally within two years (usually within nine months). So long as the skin growths are present, there is a possibility of transmitting the infection to another person. When the growths are gone, the possibility of spreading the infection is ended. Unlike herpesviruses , which can remain inactive in the body for months or years before reappearing, molluscum contagiosum does not remain in the body when the growths are gone from the skin and will not reappear on their own. As of 2010, approximately 122 million people were affected worldwide by molluscum contagiosum (1.8% of the population).

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Anti-vaccine_activism/html

Anti-vaccine activism

Anti-vaccine activism , also called the "anti-vax" movement, is organized activity designed to increase vaccine hesitancy , often by disseminating misinformation or disinformation . Although myths, conspiracy theories , misinformation and disinformation spread by the anti-vaccination movement and fringe doctors increases vaccine hesitancy and public debates around the medical, ethical, and legal issues related to vaccines, there is no serious hesitancy or debate within mainstream medical and scientific circles about the benefits of vaccination. Ideas that would eventually coalesce into anti-vaccine activism have existed for longer than vaccines themselves. Some philosophical approaches (e.g. homeopathy , vitalism ) are incompatible with the microbiological paradigm that explains how the immune system and vaccines work. Vaccine hesitancy and anti-vaccine activism exist within a broader context that involves cultural tradition, religious belief, approaches to health and disease, and political affiliation. Opposition to variolation for smallpox (a predecessor to vaccination) was organized as early as the 1820s around the premise that vaccination was unnatural and an attempt to thwart divine judgment. Religious arguments against inoculation , the earliest arguments against vaccination, were soon advanced. For example, in a 1722 sermon entitled "The Dangerous and Sinful Practice of Inoculation", the English theologian Reverend Edmund Massey argued that diseases are sent by God to punish sin and that any attempt to prevent smallpox via inoculation is a "diabolical operation". It was customary at the time for popular preachers to publish sermons, which reached a wide audience. This was the case with Massey, whose sermon reached North America, where there was early religious opposition, particularly by John Williams . A greater source of opposition there was William Douglass , a medical graduate of Edinburgh University and a Fellow of the Royal Society , who had settled in Boston. : 114–22 Vaccination itself was invented by British physician Edward Jenner , who published his findings on the efficacy of the practice for smallpox in 1798. By 1801, the practice had been widely endorsed in the scientific community, and by several world leaders. Philadelphia physician John Redman Coxe , noting that even then false accounts were circulated of negative effects of vaccination, wrote, "Such are the falsehoods which impede the progress of the brightest discovery which has ever been made! But the contest is in vain! Time has drawn aside the veil which obstructed our knowledge of this invaluable blessing; and in the examples of the Emperor of Constantinople, of the Dowager Empress of Russia, and the King of Spain, we may date the downfall of further opposition." Coxe's expectation of an end to opposition to vaccination proved premature, and through much of the nineteenth century, the principles, practices and impact of vaccination were matters of active scientific debate. The principles behind vaccination were not clearly understood until the end of the nineteenth century. The importance of hygiene in the preparation, storage, and administration of vaccines was not always understood or practiced. Reliable statistics on vaccine efficacy and side effects were difficult to obtain before the 1930s. In the United Kingdom , the Compulsory Vaccination Act of 1853 required that every child be vaccinated within three or four months of birth. It set a precedent for the state regulation of physical bodies, and was fiercely resisted. The following year, in 1854, John Gibbs published the first anti-compulsory-vaccination pamphlet, Our Medical Liberties . By the 1860s, anti-vaccinationism in Britain was active in the working class, labor aristocracy, and lower middle class. It had become associated with alternative medicine and was part of a larger culture of social and political dissent that included both labor unions and religious dissenters. In June 1867, the publication "Human Nature" campaigned in the United Kingdom against "The Vaccination Humbug", reporting that many petitions had been presented to Parliament against Compulsory Vaccination for smallpox , including from parents who alleged that their children had died through the procedure, and complaining that these petitions had not been made public. The journal reported the formation of the Anti-Compulsory Vaccination League "To overthrow this huge piece of physiological absurdity and medical tyranny", and quoted Richard Gibbs (a cousin of John Gibbs) who ran the Free Hospital at the same address as stating "I believe we have hundreds of cases here, from being poisoned with vaccination, I deem incurable. One member of a family dating syphilitic symptoms from the time of vaccination, when all the other members of the family have been clear. We strongly advise parents to go to prison, rather than submit to have their helpless offspring inoculated with scrofula, syphilis, and mania". Notable members of the Anti-Compulsory Vaccination League included James Burns , George Dornbusch and Charles Thomas Pearce . After the death of Richard B. Gibbs in 1871, the Anti-Compulsory Vaccination League "languished" until 1876 when it was revived under the leadership of Mary Hume-Rothery and the Rev. W. Hume-Rothery. The Anti-Compulsory Vaccination League published the Occasional Circular which later merged into the National Anti-Compulsory Vaccination Reporter . In the United States, many states and local school boards established immunization requirements, beginning with a compulsory school vaccination law in Massachusetts in 1855. The Anti-Vaccination Society of America was founded in 1879, after a visit to the United States by British anti-vaccine activist William Tebb , and opposed compulsory smallpox vaccination for smallpox from the final decades of the 19th century through the 1910s. During this period, smallpox vaccination was the only form of vaccination that was widely practiced, and the society published a periodical opposing it, called Vaccination . A series of American legal cases, beginning in various states and culminating with that of Henning Jacobson of Massachusetts in 1905, upheld the mandating of compulsory smallpox vaccination for the good of the public. The court ruled in Jacobson v. Massachusetts that "the liberty secured by the Constitution of the United States to every person within its jurisdiction does not import an absolute right in each person to be, at all times and in all circumstances, wholly freed from restraint. There are manifold restraints to which every person is necessarily subject for the common good". In 1880, William Tebb enlarged and reorganized the Anti-Compulsory Vaccination League in the UK with the formation of the London Society for the Abolition of Compulsory Vaccination, with William Young as secretary. The Vaccination Inquirer , established by Tebb in 1879, was adopted as the official organ of the Society. A series of fourteen "Vaccination Tracts" was begun by Young in 1877 and completed by Garth Wilkinson in 1879. William White was the first editor of the Vaccination Inquirer and after his death in 1885, he was succeeded by Alfred Milnes. Frances Hoggan and her husband authored an article for the Vaccination Inquirer in September 1883 which argued against compulsory vaccination. The London Society focused on lobbying parliamentary support in the 1880s and early 1890s. They gained support from several members of the House of Commons of which the most prominent was Peter Alfred Taylor , the member for Leicester , which was described as the "Mecca of antivaccination". The UK movement grew, and as the influence of the London Society overshadowed the Hume-Rotherys and it took the national lead, it was decided in February 1896 to re-form the Society as The National Anti-Vaccination League . Arthur Phelps was elected as president. In 1898, the league took on a school leaver named Lily Loat , who was elected as the league's Secretary by 1909. In 1906, George Bernard Shaw wrote a supportive letter to the National Anti-Vaccination League, equating methods of vaccination with "rubbing the contents of the dustpan into the wound". In 1908, the Anti-Vaccination League of America was created by Charles M. Higgins and industrialist John Pitcairn Jr. , with anti-vaccination campaigns focused on New York and Pennsylvania . Members were opposed to compulsory vaccination laws. Higgins was the League's chief spokesman and pamphleteer. Historian James Colgrove noted that Higgins "attempted to overturn the New York State's law mandating vaccination of students in public schools". The League should not be confused with the Anti-Vaccination Society of America , that was formed in 1879. Higgins was criticized by medical experts for spreading misinformation and ignoring facts as to the efficacy of vaccination. The League dissolved after the death of Higgins in 1929. In the United Kingdom , the Compulsory Vaccination Act of 1853 required that every child be vaccinated within three or four months of birth. It set a precedent for the state regulation of physical bodies, and was fiercely resisted. The following year, in 1854, John Gibbs published the first anti-compulsory-vaccination pamphlet, Our Medical Liberties . By the 1860s, anti-vaccinationism in Britain was active in the working class, labor aristocracy, and lower middle class. It had become associated with alternative medicine and was part of a larger culture of social and political dissent that included both labor unions and religious dissenters. In June 1867, the publication "Human Nature" campaigned in the United Kingdom against "The Vaccination Humbug", reporting that many petitions had been presented to Parliament against Compulsory Vaccination for smallpox , including from parents who alleged that their children had died through the procedure, and complaining that these petitions had not been made public. The journal reported the formation of the Anti-Compulsory Vaccination League "To overthrow this huge piece of physiological absurdity and medical tyranny", and quoted Richard Gibbs (a cousin of John Gibbs) who ran the Free Hospital at the same address as stating "I believe we have hundreds of cases here, from being poisoned with vaccination, I deem incurable. One member of a family dating syphilitic symptoms from the time of vaccination, when all the other members of the family have been clear. We strongly advise parents to go to prison, rather than submit to have their helpless offspring inoculated with scrofula, syphilis, and mania". Notable members of the Anti-Compulsory Vaccination League included James Burns , George Dornbusch and Charles Thomas Pearce . After the death of Richard B. Gibbs in 1871, the Anti-Compulsory Vaccination League "languished" until 1876 when it was revived under the leadership of Mary Hume-Rothery and the Rev. W. Hume-Rothery. The Anti-Compulsory Vaccination League published the Occasional Circular which later merged into the National Anti-Compulsory Vaccination Reporter . In the United States, many states and local school boards established immunization requirements, beginning with a compulsory school vaccination law in Massachusetts in 1855. The Anti-Vaccination Society of America was founded in 1879, after a visit to the United States by British anti-vaccine activist William Tebb , and opposed compulsory smallpox vaccination for smallpox from the final decades of the 19th century through the 1910s. During this period, smallpox vaccination was the only form of vaccination that was widely practiced, and the society published a periodical opposing it, called Vaccination . A series of American legal cases, beginning in various states and culminating with that of Henning Jacobson of Massachusetts in 1905, upheld the mandating of compulsory smallpox vaccination for the good of the public. The court ruled in Jacobson v. Massachusetts that "the liberty secured by the Constitution of the United States to every person within its jurisdiction does not import an absolute right in each person to be, at all times and in all circumstances, wholly freed from restraint. There are manifold restraints to which every person is necessarily subject for the common good". In 1880, William Tebb enlarged and reorganized the Anti-Compulsory Vaccination League in the UK with the formation of the London Society for the Abolition of Compulsory Vaccination, with William Young as secretary. The Vaccination Inquirer , established by Tebb in 1879, was adopted as the official organ of the Society. A series of fourteen "Vaccination Tracts" was begun by Young in 1877 and completed by Garth Wilkinson in 1879. William White was the first editor of the Vaccination Inquirer and after his death in 1885, he was succeeded by Alfred Milnes. Frances Hoggan and her husband authored an article for the Vaccination Inquirer in September 1883 which argued against compulsory vaccination. The London Society focused on lobbying parliamentary support in the 1880s and early 1890s. They gained support from several members of the House of Commons of which the most prominent was Peter Alfred Taylor , the member for Leicester , which was described as the "Mecca of antivaccination". The UK movement grew, and as the influence of the London Society overshadowed the Hume-Rotherys and it took the national lead, it was decided in February 1896 to re-form the Society as The National Anti-Vaccination League . Arthur Phelps was elected as president. In 1898, the league took on a school leaver named Lily Loat , who was elected as the league's Secretary by 1909. In 1906, George Bernard Shaw wrote a supportive letter to the National Anti-Vaccination League, equating methods of vaccination with "rubbing the contents of the dustpan into the wound". In 1908, the Anti-Vaccination League of America was created by Charles M. Higgins and industrialist John Pitcairn Jr. , with anti-vaccination campaigns focused on New York and Pennsylvania . Members were opposed to compulsory vaccination laws. Higgins was the League's chief spokesman and pamphleteer. Historian James Colgrove noted that Higgins "attempted to overturn the New York State's law mandating vaccination of students in public schools". The League should not be confused with the Anti-Vaccination Society of America , that was formed in 1879. Higgins was criticized by medical experts for spreading misinformation and ignoring facts as to the efficacy of vaccination. The League dissolved after the death of Higgins in 1929. Anti-vaccine activism ebbed for much of the twentieth century, but never completely vanished. In the UK, the National Anti-Vaccination League continued to publish new issues of its journal until 1972, by which time the global campaign for smallpox eradication through vaccination had made the disease so uncommon that compulsory vaccination for smallpox was no longer required in the United Kingdom. New vaccines were developed and used against diseases such as diphtheria and whooping cough . In the UK, these were often introduced on a voluntary basis, without arousing the same kind of anti-vaccination response that had accompanied compulsory smallpox vaccination. In the United States, numerous measles outbreaks occurred in the 1960s and 1970s, and were shown to be more frequent in states that lacked mandatory vaccination requirements. This led to calls in the 1970s for a national level vaccination requirement for children entering schools. Joseph A. Califano Jr. appealed to state governors, and by 1980, all 50 states legally required vaccination for school entrance. Many of these laws allowed exemptions in response to lobbyists. In New York State, a 1967 law allowed exemptions from receiving polio vaccine for members of religious organizations such as Christian Scientists . Anti-vaccine activism in the 2000s regained prominence through exploratory research based on 12 cases that made claims about a link between the MMR vaccine and autism . These claims were subsequently extensively investigated and found to be false, and the original study turned out to be based on faked data. The scientific consensus is that there is no link between the MMR vaccine and autism, and that the MMR vaccine's benefits in preventing measles , mumps , and rubella greatly outweigh its potential risks. The idea of an autism link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, which Dennis K Flaherty at the University of Charleston characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper authored by Andrew Wakefield and published in The Lancet falsely claimed the vaccine was linked to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccine activists. The claims in the paper were widely reported, leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continued in anti-vaccination propaganda for the next three decades despite being refuted, was estimated to have led to an increase in the incidence of measles and mumps , resulting in deaths and serious permanent injuries. Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention , the American Academy of Pediatrics , the Institute of Medicine of the US National Academy of Sciences , the UK National Health Service , and the Cochrane Library all found no link between the MMR vaccine and autism. Physicians, medical journals, and editors have described Wakefield's actions as fraudulent and tied them to epidemics and deaths. An investigation by journalist Brian Deer found that Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest , had manipulated evidence, and had broken other ethical codes. After a subsequent 2.5-year investigation, the General Medical Council ruled that Wakefield had acted "dishonestly and irresponsibly" in doing his research, carrying out unauthorized procedures for which he was not qualified, and acting with "callous disregard" for the children involved. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010, and was struck off the Medical Register , meaning he could no longer practise as a physician in the UK. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet ' s editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. In January 2011, Deer published a series of reports in the British Medical Journal , in which a signed editorial stated of the journalist, "It has taken the diligent scepticism of one man, standing outside medicine and science, to show that the paper was in fact an elaborate fraud." A 2011 journal article described the vaccine-autism connection as "the most damaging medical hoax of the last 100 years". Wakefield continues to promote anti-vaccine beliefs and conspiracy theories in the United States. In February 2015, Wakefield denied that he bore any responsibility for the measles epidemic that started at Disneyland among unvaccinated children that year. He also reaffirmed his discredited belief that "MMR contributes to the current autism epidemic". By that time, at least 166 measles cases had been reported. Paul Offit disagreed, saying that the outbreak was "directly related to Dr. Wakefield's theory". Wakefield and other anti-vaccine activists were active in the American-Somali community in Minnesota, where a drop in vaccination rates was followed by the largest measles outbreak in the state in nearly 30 years in 2017. The anti-vaccination movement was historically apolitical, but in the 2010s and 2020s the movement in the United States has increasingly targeted conservatives. As measles outbreaks increased, so did calls to eliminate exemptions from vaccine administration. As of 2015, 19 American states had suggested legislation to eliminate or increase the difficulty of exemptions, including California. Concurrently, American anti-vaccine activists reached out to libertarian and right-leaning groups such as the Tea Party movement to broaden their base. While earlier anti-vaccination activists focused on health impacts and safety of vaccines, recent themes increasingly involve philosophical arguments about liberty, medical freedom and parental rights. With the growing anti-vaccine movement from the 2010s onwards, the United States has seen a resurgence of certain vaccine-preventable diseases . The measles virus lost its elimination status in the US as the number of measles cases continued to rise in the late 2010s with a total of 17 outbreaks in 2018 and 465 outbreaks in 2019 (as of 4 April 2019). Vaccine hesitancy led to declining rates of vaccination for measles, culminating in the 2019–2020 measles outbreaks . The most significant of these in proportion to national population was the 2019 Samoa measles outbreak . In July 2018, two 12-month-old children died in Samoa after receiving incorrectly prepared MMR vaccinations. These two deaths were picked up by anti-vaccine groups and used to incite fear towards vaccination on social media, causing the government to suspend its measles vaccination programme for ten months, despite advice from the WHO. The incident caused many Samoan residents to lose trust in the healthcare system. UNICEF and the World Health Organization estimate that the measles vaccination rate in Samoa fell from 74% in 2017 to 34% in 2018, similar to some of the poorest countries in Africa. In August 2019, an infected passenger on one of the more than 8,000 annual flights between New Zealand and Samoa probably brought the disease from Auckland to Upolu . A full outbreak of measles began on the island in October 2019 and continued for the next four months. As of 6 January 2020, there were over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,874. Over three per cent of the population were infected. The cause of the outbreak was attributed to decreased vaccination rates, from 74% in 2017 to 31–34% in 2018, even though nearby islands had rates near 99%. a rate of 14.3 deaths per 1000 infected) and 5,520 cases (2.75% of the population) of measles in Samoa. 61 out of the first 70 deaths were four years old and under, and all but seven were under 15. After the outbreak, anti-vaxxers employed racist tropes and misinformation to credit the scores of measles deaths to poverty and poor nutrition or even to the vaccine itself, but this has been discounted by the international emergency medical support that arrived in November and December. There was no evidence of acute malnutrition, clinical vitamin A deficiency, or immune deficiency as claimed by various anti-vaxxers. During the COVID-19 pandemic , anti-vaccine activists undertook various efforts to hinder people who wanted to receive the vaccines, with such activities occurring in countries including Australia, Israel, the United Kingdom, and the United States. These included attempts to physically blockade vaccination sites, and making false reservations for vaccination appointments to clog up vaccination booking systems. Protests were also organized by the activists to raise awareness for their cause. In some instances, anti-vaccine rhetoric has been traced to state-sponsored internet troll activities designed to create social dissension. Worldwide, foreign disinformation campaigns have been associated with declining vaccination rates in target countries. Anti-vaccine activism online both before and during the pandemic has been linked to extreme levels of falsehoods, rumours, hoaxes, and conspiracy theories. Anti-vaccine activists have falsely claimed in social media posts that numerous deaths or injuries had to do with reactions to vaccines. In one highly publicized instance in early 2023, after Buffalo Bills football player Damar Hamlin experienced an in-game episode of commotio cordis , there was an increase in rhetoric and disinformation from figures such as Charlie Kirk and Drew Pinsky making unfounded claims about Hamlin's cardiac arrest and COVID-19 vaccines . In another 2023 incident, college basketball player Bronny James experienced cardiac arrest at the Galen Center at the University of Southern California , leading to assertions that this was a result of receiving a COVID-19 vaccine ; it was later revealed that the episode had been caused by a congenital heart defect . Also, anti-vaccine activists believed Foo Fighters drummer Taylor Hawkins died in 2022 from the COVID-19 vaccine, while in actuality it was a drug overdose. In December 2023, The New York Times published a detailed investigation of the distortion and misrepresentation of the circumstances surrounding the death of 24-year-old George Watts Jr. by Robert F. Kennedy Jr. and other anti-vaccine activists. Prominent biomedical researcher Peter Hotez , asserted that he and other American scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He further attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. A 2023 study published in the Journal of the American Medical Association found "evidence of higher excess mortality for Republican voters compared with Democratic voters in Florida and Ohio after, but not before, COVID-19 vaccines were available to all adults in the US". Anti-vaccine activism in the 2000s regained prominence through exploratory research based on 12 cases that made claims about a link between the MMR vaccine and autism . These claims were subsequently extensively investigated and found to be false, and the original study turned out to be based on faked data. The scientific consensus is that there is no link between the MMR vaccine and autism, and that the MMR vaccine's benefits in preventing measles , mumps , and rubella greatly outweigh its potential risks. The idea of an autism link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, which Dennis K Flaherty at the University of Charleston characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper authored by Andrew Wakefield and published in The Lancet falsely claimed the vaccine was linked to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccine activists. The claims in the paper were widely reported, leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continued in anti-vaccination propaganda for the next three decades despite being refuted, was estimated to have led to an increase in the incidence of measles and mumps , resulting in deaths and serious permanent injuries. Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention , the American Academy of Pediatrics , the Institute of Medicine of the US National Academy of Sciences , the UK National Health Service , and the Cochrane Library all found no link between the MMR vaccine and autism. Physicians, medical journals, and editors have described Wakefield's actions as fraudulent and tied them to epidemics and deaths. An investigation by journalist Brian Deer found that Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest , had manipulated evidence, and had broken other ethical codes. After a subsequent 2.5-year investigation, the General Medical Council ruled that Wakefield had acted "dishonestly and irresponsibly" in doing his research, carrying out unauthorized procedures for which he was not qualified, and acting with "callous disregard" for the children involved. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010, and was struck off the Medical Register , meaning he could no longer practise as a physician in the UK. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet ' s editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. In January 2011, Deer published a series of reports in the British Medical Journal , in which a signed editorial stated of the journalist, "It has taken the diligent scepticism of one man, standing outside medicine and science, to show that the paper was in fact an elaborate fraud." A 2011 journal article described the vaccine-autism connection as "the most damaging medical hoax of the last 100 years". Wakefield continues to promote anti-vaccine beliefs and conspiracy theories in the United States. In February 2015, Wakefield denied that he bore any responsibility for the measles epidemic that started at Disneyland among unvaccinated children that year. He also reaffirmed his discredited belief that "MMR contributes to the current autism epidemic". By that time, at least 166 measles cases had been reported. Paul Offit disagreed, saying that the outbreak was "directly related to Dr. Wakefield's theory". Wakefield and other anti-vaccine activists were active in the American-Somali community in Minnesota, where a drop in vaccination rates was followed by the largest measles outbreak in the state in nearly 30 years in 2017. The anti-vaccination movement was historically apolitical, but in the 2010s and 2020s the movement in the United States has increasingly targeted conservatives. As measles outbreaks increased, so did calls to eliminate exemptions from vaccine administration. As of 2015, 19 American states had suggested legislation to eliminate or increase the difficulty of exemptions, including California. Concurrently, American anti-vaccine activists reached out to libertarian and right-leaning groups such as the Tea Party movement to broaden their base. While earlier anti-vaccination activists focused on health impacts and safety of vaccines, recent themes increasingly involve philosophical arguments about liberty, medical freedom and parental rights. With the growing anti-vaccine movement from the 2010s onwards, the United States has seen a resurgence of certain vaccine-preventable diseases . The measles virus lost its elimination status in the US as the number of measles cases continued to rise in the late 2010s with a total of 17 outbreaks in 2018 and 465 outbreaks in 2019 (as of 4 April 2019). Vaccine hesitancy led to declining rates of vaccination for measles, culminating in the 2019–2020 measles outbreaks . The most significant of these in proportion to national population was the 2019 Samoa measles outbreak . In July 2018, two 12-month-old children died in Samoa after receiving incorrectly prepared MMR vaccinations. These two deaths were picked up by anti-vaccine groups and used to incite fear towards vaccination on social media, causing the government to suspend its measles vaccination programme for ten months, despite advice from the WHO. The incident caused many Samoan residents to lose trust in the healthcare system. UNICEF and the World Health Organization estimate that the measles vaccination rate in Samoa fell from 74% in 2017 to 34% in 2018, similar to some of the poorest countries in Africa. In August 2019, an infected passenger on one of the more than 8,000 annual flights between New Zealand and Samoa probably brought the disease from Auckland to Upolu . A full outbreak of measles began on the island in October 2019 and continued for the next four months. As of 6 January 2020, there were over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,874. Over three per cent of the population were infected. The cause of the outbreak was attributed to decreased vaccination rates, from 74% in 2017 to 31–34% in 2018, even though nearby islands had rates near 99%. a rate of 14.3 deaths per 1000 infected) and 5,520 cases (2.75% of the population) of measles in Samoa. 61 out of the first 70 deaths were four years old and under, and all but seven were under 15. After the outbreak, anti-vaxxers employed racist tropes and misinformation to credit the scores of measles deaths to poverty and poor nutrition or even to the vaccine itself, but this has been discounted by the international emergency medical support that arrived in November and December. There was no evidence of acute malnutrition, clinical vitamin A deficiency, or immune deficiency as claimed by various anti-vaxxers. During the COVID-19 pandemic , anti-vaccine activists undertook various efforts to hinder people who wanted to receive the vaccines, with such activities occurring in countries including Australia, Israel, the United Kingdom, and the United States. These included attempts to physically blockade vaccination sites, and making false reservations for vaccination appointments to clog up vaccination booking systems. Protests were also organized by the activists to raise awareness for their cause. In some instances, anti-vaccine rhetoric has been traced to state-sponsored internet troll activities designed to create social dissension. Worldwide, foreign disinformation campaigns have been associated with declining vaccination rates in target countries. Anti-vaccine activism online both before and during the pandemic has been linked to extreme levels of falsehoods, rumours, hoaxes, and conspiracy theories. Anti-vaccine activists have falsely claimed in social media posts that numerous deaths or injuries had to do with reactions to vaccines. In one highly publicized instance in early 2023, after Buffalo Bills football player Damar Hamlin experienced an in-game episode of commotio cordis , there was an increase in rhetoric and disinformation from figures such as Charlie Kirk and Drew Pinsky making unfounded claims about Hamlin's cardiac arrest and COVID-19 vaccines . In another 2023 incident, college basketball player Bronny James experienced cardiac arrest at the Galen Center at the University of Southern California , leading to assertions that this was a result of receiving a COVID-19 vaccine ; it was later revealed that the episode had been caused by a congenital heart defect . Also, anti-vaccine activists believed Foo Fighters drummer Taylor Hawkins died in 2022 from the COVID-19 vaccine, while in actuality it was a drug overdose. In December 2023, The New York Times published a detailed investigation of the distortion and misrepresentation of the circumstances surrounding the death of 24-year-old George Watts Jr. by Robert F. Kennedy Jr. and other anti-vaccine activists. Prominent biomedical researcher Peter Hotez , asserted that he and other American scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He further attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. A 2023 study published in the Journal of the American Medical Association found "evidence of higher excess mortality for Republican voters compared with Democratic voters in Florida and Ohio after, but not before, COVID-19 vaccines were available to all adults in the US". In a 2002 paper in the British Medical Journal , two medical historians suggested that the arguments made against the safety and effectiveness of vaccines in the late 20th century are similar to those of the early anti-vaccinationists. Both the 19th and 20th century arguments included "vaccine safety issues, vaccine failures, infringement of personal liberty, and an unholy alliance between the medical establishment and the government to reap huge profits for the medical establishment at the expense of the public." However, the authors only considered the use of "newspaper articles and letters, books, journals, and pamphlets to warn against the dangers of vaccination", and did not address the impact of the internet. Comments on YouTube videos during the COVID-19 pandemic clustered similarly around "concerns about side-effects, effectiveness, and lack of trust in corporations and government". In some instances, anti-vaccine organizations have used names intended to sound non-partisan on the issue: e.g. National Vaccine Information Center (USA), Vaccination Risk Awareness Network (Canada), Australian Vaccination Network. In November 2013 the Australian Vaccination Network was ordered by the New South Wales Administrative Decisions Tribunal to change their name so that consumers are aware of the anti-vaccination nature of the group. Lateline reported that former AVN president Meryl Dorey "claimed she was a victim of hate groups and vested interests" in response to the ruling. Although physicians and nurses are still rated as the most trusted source for vaccine information, some vaccine-hesitant individuals report being more comfortable discussing vaccines with providers of complementary and alternative (CAM) treatments. With the rise of the internet, many people have turned online for medical information. In some instances, anti-vaccine activists seek to steer people away from vaccination and health-care providers and towards alternative medicines sold by certain of the activists. Anti-vaccination writings on the internet have been argued to be characterized by a number of differences from medical and scientific literature. These include: For example, a 2020 study examined Instagram posts related to the HPV vaccine , which can prevent some types of cancer. Anti-vaccine posts were more likely than pro-vaccine posts to be sent by non-healthcare individuals, to include personal narratives, and to reference other Instagram users, links, or reposts. Anti-vaccine posts were also more likely to involve concealment or distortion, particularly conspiracy theories and unsubstantiated claims. 72.3% of antivaccine posts made inaccurate claims, including exaggerating the risks of vaccines and minimizing risks of disease. A number of specific disinformation tactics have been noted in anti-vaccination messaging, including: Information is more likely to be believed after repeated exposure. Disinformers use this illusory truth effect as a tactic, repeating false information to make it feel familiar and influence belief. Anti-vaccine activists have leveraged social media to develop interconnected networks of influencers that shape people's opinion, recruit allies, impact policy and monetize vaccine-related disinformation. In 2022, the Journal of Communication published a study of the political economy underlying vaccine disinformation. Researchers identified 59 English-language "actors" that provided "almost exclusively anti-vaccination publications". Their websites monetized disinformation through appeals for donations, sales of content-based media and other merchandise, third-party advertising, and membership fees. Some maintained a group of linked websites, attracting visitors with one site and appealing for money and selling merchandise on others. Their activities to gain attention and obtain funding displayed a "hybrid monetization strategy". They attracted attention by combining eye-catching aspects of "junk news" and online celebrity promotion. At the same time, they developed campaign-specific communities to publicize and legitimize their position, similar to radical social movements. In the United States, the Vaccine Adverse Event Reporting System (VAERS) is used to gather information on potential vaccine adverse reactions, but is susceptible to unverified reports, misattribution, underreporting , and inconsistent data quality . Raw, unverified data from VAERS has often been used by the anti-vaccine community to justify misinformation regarding the safety of vaccines; it is generally not possible to find out from VAERS data if a vaccine caused an adverse event, or how common the event might be. Since Republicans gained a majority in the House in January 2023, the House Judiciary Committee has used legal action to actively oppose both disinformation research and government involvement in fighting disinformation. One of the projects targeted is the Virality Project, which has examined the spread of false claims about vaccines. The House Judiciary Committee has sent letters, subpoenas, and threats of legal action to researchers, demanding notes, emails and other records from researchers and even student interns, dating back to 2015. Institutions include the Stanford Internet Observatory at Stanford University , the University of Washington , the Atlantic Council 's Digital Forensic Research Lab and the social media analytics firm Graphika. Researchers emphasize that they have academic freedom to study disinformation as well as freedom of speech to report their results. Despite conservative claims that the government acted to censor speech online, "no evidence has emerged that government officials coerced the companies to take action against accounts". The actions of the House Judiciary Committee have been described as an "attempt to chill research," creating a "chilling effect" through increased time demands, legal costs and online harassment of researchers. Persons undertaking efforts to counter vaccine misinformation, including public health experts who use social media, have been targeted for harassment by anti-vaccine activists. For example, Slovakian physician Vladimír Krčméry was a prominent member of the government advisory team during the COVID-19 pandemic in Slovakia , and was the first person to in that country to receive a COVID-19 vaccine . Due to his prominent role in the vaccination campaign, Krčméry and his family became a target of anti-vaccine activists, who physically threatened him and his family. In June 2023, Texas-based physician and researcher Peter Hotez tweeted his concerns about Robert F. Kennedy Jr. sharing misinformation about vaccines on Joe Rogan 's podcast. Rogan, Kennedy, and Twitter owner Elon Musk asked Hotez to participate in a debate on the podcast. Upon declining the invitation, Hotez was harassed by their fans, with anti-vaccine activist Alex Rosen confronting him at his home. In his book The Deadly Rise of Anti-science: A Scientist's Warning , Hotez describes how he and other scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. At the extreme end, opposition to vaccination has resulted in substantial violence against vaccinators. In Pakistan, "more than 200 polio team workers have lost their lives" (team members include not only vaccinators but police and security personnel) from "targeted killing and terrorism" while working on polio vaccination campaigns. In a 2002 paper in the British Medical Journal , two medical historians suggested that the arguments made against the safety and effectiveness of vaccines in the late 20th century are similar to those of the early anti-vaccinationists. Both the 19th and 20th century arguments included "vaccine safety issues, vaccine failures, infringement of personal liberty, and an unholy alliance between the medical establishment and the government to reap huge profits for the medical establishment at the expense of the public." However, the authors only considered the use of "newspaper articles and letters, books, journals, and pamphlets to warn against the dangers of vaccination", and did not address the impact of the internet. Comments on YouTube videos during the COVID-19 pandemic clustered similarly around "concerns about side-effects, effectiveness, and lack of trust in corporations and government". In some instances, anti-vaccine organizations have used names intended to sound non-partisan on the issue: e.g. National Vaccine Information Center (USA), Vaccination Risk Awareness Network (Canada), Australian Vaccination Network. In November 2013 the Australian Vaccination Network was ordered by the New South Wales Administrative Decisions Tribunal to change their name so that consumers are aware of the anti-vaccination nature of the group. Lateline reported that former AVN president Meryl Dorey "claimed she was a victim of hate groups and vested interests" in response to the ruling. Although physicians and nurses are still rated as the most trusted source for vaccine information, some vaccine-hesitant individuals report being more comfortable discussing vaccines with providers of complementary and alternative (CAM) treatments. With the rise of the internet, many people have turned online for medical information. In some instances, anti-vaccine activists seek to steer people away from vaccination and health-care providers and towards alternative medicines sold by certain of the activists. Anti-vaccination writings on the internet have been argued to be characterized by a number of differences from medical and scientific literature. These include: For example, a 2020 study examined Instagram posts related to the HPV vaccine , which can prevent some types of cancer. Anti-vaccine posts were more likely than pro-vaccine posts to be sent by non-healthcare individuals, to include personal narratives, and to reference other Instagram users, links, or reposts. Anti-vaccine posts were also more likely to involve concealment or distortion, particularly conspiracy theories and unsubstantiated claims. 72.3% of antivaccine posts made inaccurate claims, including exaggerating the risks of vaccines and minimizing risks of disease. A number of specific disinformation tactics have been noted in anti-vaccination messaging, including: Information is more likely to be believed after repeated exposure. Disinformers use this illusory truth effect as a tactic, repeating false information to make it feel familiar and influence belief. Anti-vaccine activists have leveraged social media to develop interconnected networks of influencers that shape people's opinion, recruit allies, impact policy and monetize vaccine-related disinformation. In 2022, the Journal of Communication published a study of the political economy underlying vaccine disinformation. Researchers identified 59 English-language "actors" that provided "almost exclusively anti-vaccination publications". Their websites monetized disinformation through appeals for donations, sales of content-based media and other merchandise, third-party advertising, and membership fees. Some maintained a group of linked websites, attracting visitors with one site and appealing for money and selling merchandise on others. Their activities to gain attention and obtain funding displayed a "hybrid monetization strategy". They attracted attention by combining eye-catching aspects of "junk news" and online celebrity promotion. At the same time, they developed campaign-specific communities to publicize and legitimize their position, similar to radical social movements. In the United States, the Vaccine Adverse Event Reporting System (VAERS) is used to gather information on potential vaccine adverse reactions, but is susceptible to unverified reports, misattribution, underreporting , and inconsistent data quality . Raw, unverified data from VAERS has often been used by the anti-vaccine community to justify misinformation regarding the safety of vaccines; it is generally not possible to find out from VAERS data if a vaccine caused an adverse event, or how common the event might be. Since Republicans gained a majority in the House in January 2023, the House Judiciary Committee has used legal action to actively oppose both disinformation research and government involvement in fighting disinformation. One of the projects targeted is the Virality Project, which has examined the spread of false claims about vaccines. The House Judiciary Committee has sent letters, subpoenas, and threats of legal action to researchers, demanding notes, emails and other records from researchers and even student interns, dating back to 2015. Institutions include the Stanford Internet Observatory at Stanford University , the University of Washington , the Atlantic Council 's Digital Forensic Research Lab and the social media analytics firm Graphika. Researchers emphasize that they have academic freedom to study disinformation as well as freedom of speech to report their results. Despite conservative claims that the government acted to censor speech online, "no evidence has emerged that government officials coerced the companies to take action against accounts". The actions of the House Judiciary Committee have been described as an "attempt to chill research," creating a "chilling effect" through increased time demands, legal costs and online harassment of researchers. Persons undertaking efforts to counter vaccine misinformation, including public health experts who use social media, have been targeted for harassment by anti-vaccine activists. For example, Slovakian physician Vladimír Krčméry was a prominent member of the government advisory team during the COVID-19 pandemic in Slovakia , and was the first person to in that country to receive a COVID-19 vaccine . Due to his prominent role in the vaccination campaign, Krčméry and his family became a target of anti-vaccine activists, who physically threatened him and his family. In June 2023, Texas-based physician and researcher Peter Hotez tweeted his concerns about Robert F. Kennedy Jr. sharing misinformation about vaccines on Joe Rogan 's podcast. Rogan, Kennedy, and Twitter owner Elon Musk asked Hotez to participate in a debate on the podcast. Upon declining the invitation, Hotez was harassed by their fans, with anti-vaccine activist Alex Rosen confronting him at his home. In his book The Deadly Rise of Anti-science: A Scientist's Warning , Hotez describes how he and other scientists who publicly defend vaccines have been attacked on social media, harassed with threatening emails, intimidated, and confronted physically by opponents of vaccination. He attributes the increase in aggressiveness of the anti-vaccination movement to the influence of the extreme wing of the Republican Party. Hotez estimates that roughly 200,000 preventable deaths from COVID-19, mainly among Republicans, occurred in the US because of refusal to be vaccinated. At the extreme end, opposition to vaccination has resulted in substantial violence against vaccinators. In Pakistan, "more than 200 polio team workers have lost their lives" (team members include not only vaccinators but police and security personnel) from "targeted killing and terrorism" while working on polio vaccination campaigns. Various efforts have been suggested and undertaken to address concerns about vaccines and counter anti-vaccine disinformation. Efforts include social media advertising campaigns, by public health organizations, in support of public health goals. Best practices for combating vaccine mis- and disinformation include addressing issues openly, clearly identifying areas of scientific consensus and areas of uncertainty, and being sensitive to the cultural and religious values of communities. In countering anti-vaccine disinformation, both factual and emotional aspects need to be addressed. Whether people will update a mistaken belief is complicated and involves psychological factors and social goals as well as accuracy of information. There is some evidence that both debunking and " pre-bunking " of disinformation can be effective, at least in the short term. Elements that may help to correct inaccurate information include: warning people before they are exposed to misinformation; high perceived credibility of message sources, affirmations of identity and social norms; graphical presentation; and focusing attention on clear core messages. Alternative explanations of a situation need to fit plausibly into the original scenario and ideally indicate why the incorrect explanation was previously thought to be correct. The cultivation of critical thinking, health and science awareness, and media literacy skills are all recommended to help people more critically assess the credibility of the information they see. People who seek out multiple reputable news sources at local and national levels are more likely to detect disinformation than those who rely on few sources from a particular viewpoint. Particularly on social media, beware of sensational headlines that appeal to emotion, fact-check information broadly (not just through your usual sources), and consider possible agendas or conflicts of interest of those relaying information. Other suggestions for countering anti-vaccine activism focus on changing the operation of social media platforms. Interventions such as accuracy nudges and source labelling change the context in which information is presented. For example, correct information can be directly presented to counter disinformation. Other possibilities include flagging or removing misleading information on social media platforms. Research suggests that a majority of individuals in the United States would support the removal of harmful misinformation posts and the suspension of accounts. This position is less popular with Republicans than Democrats. While private entities like Facebook, Twitter and Telegram could legally establish guidelines for moderation of information and disinformation on their platforms (subject to local and international laws) such companies do not have strong incentives to control disinformation or to self-regulate. Algorithms that are used to maximize user engagement and profits can lead to unbalanced, poorly sourced, and actively misleading information. Criticized for its role in vaccine hesitancy , Facebook announced in March 2019 that it would provide users with "authoritative information" on the topic of vaccines. Facebook introduced several policies chosen to reduce the impact of anti-vaccine content, without actually removing it. These included reducing the ranking of anti-vaccine sources in searches and not recommending them; rejecting ads and targeted advertising that contained vaccine misinformation; and using banners to present vaccine information from authoritative sources. A study examined the six months before and after the policy changes. It found a moderate but significant decrease in the number of likes for anti-vaccine posts following the policy changes. Likes of pro-vaccine posts were unchanged. Facebook has been criticized for not being more aggressive in countering disinformation. In response to efforts to police misinformation, anti-vaccine communities on social media have adopted coded language to refer to vaccinated persons and the vaccines themselves. Supply-side interventions reduce circulation of misinformation directly at their sources through actions such as application of social media policies, regulation, and legislation. A study published in the journal Vaccine examined advertisements posted in the three months prior to the Facebook's 2019 policy changes. It found that 54% of the anti-vaccine advertisements on Facebook were placed by just two organizations, funded by well-known anti-vaccination activists. The Children's Health Defense / World Mercury Project chaired by Robert F. Kennedy Jr. and Stop Mandatory Vaccination , run by campaigner Larry Cook, posted 54% of the advertisements. The ads often linked to commercial products, such as natural remedies and books. Kennedy was suspended from Facebook in August 2022, but reinstated in June 2023. In 2023, however, state governments that were politically aligned with anti-vaccine activists successfully sought a preliminary injunction to prevent the Biden Administration from seeking to pressure social media companies into fighting misinformation. The order issued by United States Court of Appeals for the Fifth Circuit "severely limits the ability of the White House, the surgeon general, [and] the Centers for Disease Control and Prevention... to communicate with social media companies about content related to Covid-19... that the government views as misinformation". In October 2023, this injunction was paused by the Supreme Court of the United States , pending further litigation. Algorithms and user data can be used to identify selected subgroups who can then be provided with specialized content. This type of approach has been used both by anti-vaccine activists and by health providers who hope to counter vaccine-related disinformation. For example, in the United States, the CDC's Social Vulnerability Index (SVI) has been used to identify communities that have traditionally been under-served or are at elevated risk for infection, morbidity, and mortality. Programs have been developed in such communities to address disinformation and vaccine hesitancy. Steps have been taken to counter anti-vaccine messaging by directly engaging with communities. Outreach efforts include call centers and texting campaigns, partnering with local community leaders, and holding community-based vaccine clinics. Creating digital and science literacy resources and distributing them via schools, libraries, municipal offices, churches and other community groups can help to counter misinformation in under-resourced communities. The Black Doctors Covid-19 Consortium in Philadelphia is one example of a successful direct outreach initiative. Another is the New York State Vaccine Equity Task Force. In line with the Strategic Advisory Group of Experts (SAGE)'s 3C's model, outreach to communities has focused on addressing mistrust and increasing Confidence, providing information to improve risk assessment (Complacency), and improving access to COVID-19 vaccines (Convenience). It has been necessary to counter disinformation in all three areas. Recommendations for combating vaccine disinformation include increasing the presence of trusted health agencies and credible information on social media, partnering with social media platforms to promote evidence-based public health information, and identifying and responding to emerging concerns and disinformation campaigns. Networked communities of public health officials and other stakeholders, connecting with the public through a variety of credible and trusted messengers, are recommended. Sharing of messages through such networks could help to debunk and counter highly networked and coordinated disinformation attacks. A networked community approach would differ from the current model of US public health communication, which tends to rely on a single credible messenger (e.g. Anthony Fauci ) and is susceptible to disinformation attacks. To deal with disinformation, community networks would need to address issues of liberty and human rights as well as vaccine safety, effectiveness and access. Networks could also help to show support for those attacked by anti-vaccine activists. Other suggestions for countering anti-vaccine activism focus on changing the operation of social media platforms. Interventions such as accuracy nudges and source labelling change the context in which information is presented. For example, correct information can be directly presented to counter disinformation. Other possibilities include flagging or removing misleading information on social media platforms. Research suggests that a majority of individuals in the United States would support the removal of harmful misinformation posts and the suspension of accounts. This position is less popular with Republicans than Democrats. While private entities like Facebook, Twitter and Telegram could legally establish guidelines for moderation of information and disinformation on their platforms (subject to local and international laws) such companies do not have strong incentives to control disinformation or to self-regulate. Algorithms that are used to maximize user engagement and profits can lead to unbalanced, poorly sourced, and actively misleading information. Criticized for its role in vaccine hesitancy , Facebook announced in March 2019 that it would provide users with "authoritative information" on the topic of vaccines. Facebook introduced several policies chosen to reduce the impact of anti-vaccine content, without actually removing it. These included reducing the ranking of anti-vaccine sources in searches and not recommending them; rejecting ads and targeted advertising that contained vaccine misinformation; and using banners to present vaccine information from authoritative sources. A study examined the six months before and after the policy changes. It found a moderate but significant decrease in the number of likes for anti-vaccine posts following the policy changes. Likes of pro-vaccine posts were unchanged. Facebook has been criticized for not being more aggressive in countering disinformation. In response to efforts to police misinformation, anti-vaccine communities on social media have adopted coded language to refer to vaccinated persons and the vaccines themselves. Supply-side interventions reduce circulation of misinformation directly at their sources through actions such as application of social media policies, regulation, and legislation. A study published in the journal Vaccine examined advertisements posted in the three months prior to the Facebook's 2019 policy changes. It found that 54% of the anti-vaccine advertisements on Facebook were placed by just two organizations, funded by well-known anti-vaccination activists. The Children's Health Defense / World Mercury Project chaired by Robert F. Kennedy Jr. and Stop Mandatory Vaccination , run by campaigner Larry Cook, posted 54% of the advertisements. The ads often linked to commercial products, such as natural remedies and books. Kennedy was suspended from Facebook in August 2022, but reinstated in June 2023. In 2023, however, state governments that were politically aligned with anti-vaccine activists successfully sought a preliminary injunction to prevent the Biden Administration from seeking to pressure social media companies into fighting misinformation. The order issued by United States Court of Appeals for the Fifth Circuit "severely limits the ability of the White House, the surgeon general, [and] the Centers for Disease Control and Prevention... to communicate with social media companies about content related to Covid-19... that the government views as misinformation". In October 2023, this injunction was paused by the Supreme Court of the United States , pending further litigation. Algorithms and user data can be used to identify selected subgroups who can then be provided with specialized content. This type of approach has been used both by anti-vaccine activists and by health providers who hope to counter vaccine-related disinformation. For example, in the United States, the CDC's Social Vulnerability Index (SVI) has been used to identify communities that have traditionally been under-served or are at elevated risk for infection, morbidity, and mortality. Programs have been developed in such communities to address disinformation and vaccine hesitancy. Steps have been taken to counter anti-vaccine messaging by directly engaging with communities. Outreach efforts include call centers and texting campaigns, partnering with local community leaders, and holding community-based vaccine clinics. Creating digital and science literacy resources and distributing them via schools, libraries, municipal offices, churches and other community groups can help to counter misinformation in under-resourced communities. The Black Doctors Covid-19 Consortium in Philadelphia is one example of a successful direct outreach initiative. Another is the New York State Vaccine Equity Task Force. In line with the Strategic Advisory Group of Experts (SAGE)'s 3C's model, outreach to communities has focused on addressing mistrust and increasing Confidence, providing information to improve risk assessment (Complacency), and improving access to COVID-19 vaccines (Convenience). It has been necessary to counter disinformation in all three areas. Recommendations for combating vaccine disinformation include increasing the presence of trusted health agencies and credible information on social media, partnering with social media platforms to promote evidence-based public health information, and identifying and responding to emerging concerns and disinformation campaigns. Networked communities of public health officials and other stakeholders, connecting with the public through a variety of credible and trusted messengers, are recommended. Sharing of messages through such networks could help to debunk and counter highly networked and coordinated disinformation attacks. A networked community approach would differ from the current model of US public health communication, which tends to rely on a single credible messenger (e.g. Anthony Fauci ) and is susceptible to disinformation attacks. To deal with disinformation, community networks would need to address issues of liberty and human rights as well as vaccine safety, effectiveness and access. Networks could also help to show support for those attacked by anti-vaccine activists.

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/List_of_insect-borne_diseases/html

List of insect-borne diseases

This article contains a list of insect-borne diseases . They can take the form of parasitic worms , bacteria , protozoa , viruses , or the insects directly acting as a parasite.Mosquitoes are vectors for a large number of diseases, the large majority being viral in nature. Mosquito-borne viruses fall into four major groups: Bunyavirales , Flaviviridae , Togaviridae , and Reoviridae . They can present as either arbovirus encephalitis or viral hemorrhagic fevers .Mosquitoes are vectors for a large number of diseases, the large majority being viral in nature. Mosquito-borne viruses fall into four major groups: Bunyavirales , Flaviviridae , Togaviridae , and Reoviridae . They can present as either arbovirus encephalitis or viral hemorrhagic fevers .

Wiki

Chikungunya

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

MRNA vaccine

An mRNA vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen -encoding mRNA into immune cells , which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen (such as a virus ) or by a cancer cell . These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells. Reactogenicity , the tendency of a vaccine to produce adverse reactions, is similar to that of conventional non-RNA vaccines. People susceptible to an autoimmune response may have an adverse reaction to messenger RNA vaccines. The advantages of mRNA vaccines over traditional vaccines are ease of design, speed and lower cost of production, the induction of both cellular and humoral immunity , and lack of interaction with the genomic DNA . While some messenger RNA vaccines, such as the Pfizer–BioNTech COVID-19 vaccine , have the disadvantage of requiring ultracold storage before distribution, other mRNA vaccines, such as the Moderna vaccine, or the Walvax COVID-19 vaccine used in Indonesia (and the now abandoned CureVac vaccine candidate, as well), do not have such requirements. In RNA therapeutics , messenger RNA vaccines have attracted considerable interest as COVID-19 vaccines . In December 2020, Pfizer–BioNTech and Moderna obtained authorization for their mRNA-based COVID-19 vaccines. On 2 December, the UK Medicines and Healthcare products Regulatory Agency (MHRA) became the first medicines regulator to approve an mRNA vaccine, authorizing the Pfizer–BioNTech vaccine for widespread use. On 11 December, the US Food and Drug Administration (FDA) issued an emergency use authorization for the Pfizer–BioNTech vaccine and a week later similarly authorized the Moderna vaccine. In 2023 the Nobel Prize in Physiology or Medicine was awarded to Katalin Karikó and Drew Weissman for their discoveries concerning modified nucleosides that enabled the development of effective mRNA vaccines against COVID-19. The first successful transfection of designed mRNA packaged within a liposomal nanoparticle into a cell was published in 1989. "Naked" (or unprotected) lab-made mRNA was injected a year later into the muscle of mice. These studies were the first evidence that in vitro transcribed mRNA with a chosen gene was able to deliver the genetic information to produce a desired protein within living cell tissue and led to the concept proposal of messenger RNA vaccines. Liposome-encapsulated mRNA encoding a viral antigen was shown in 1993 to stimulate T cells in mice. The following year self-amplifying mRNA was developed by including both a viral antigen and replicase encoding gene. The method was used in mice to elicit both a humoral and cellular immune response against a viral pathogen. The next year mRNA encoding a tumor antigen was shown to elicit a similar immune response against cancer cells in mice. The first human clinical trial using ex vivo dendritic cells transfected with mRNA encoding tumor antigens ( therapeutic cancer mRNA vaccine ) was started in 2001. Four years later, the successful use of modified nucleosides as a method to transport mRNA inside cells without setting off the body's defense system was reported. Clinical trial results of an mRNA vaccine directly injected into the body against cancer cells were reported in 2008. BioNTech in 2008, and Moderna in 2010, were founded to develop mRNA biotechnologies. The US research agency DARPA launched at this time the biotechnology research program ADEPT to develop emerging technologies for the US military . The agency recognized the potential of nucleic acid technology for defense against pandemics and began to invest in the field. DARPA grants were seen as a vote of confidence that in turn encouraged other government agencies and private investors to invest in mRNA technology. DARPA awarded at the time a $25 million grant to Moderna. The first human clinical trials using an mRNA vaccine against an infectious agent ( rabies ) began in 2013. Over the next few years, clinical trials of mRNA vaccines for a number of other viruses were started. mRNA vaccines for human use were studied for infectious agents such as influenza , Zika virus , cytomegalovirus , and Chikungunya virus . The COVID-19 pandemic , and sequencing of the causative virus SARS-CoV-2 at the beginning of 2020, led to the rapid development of the first approved mRNA vaccines. BioNTech and Moderna in December of the same year obtained approval for their mRNA-based COVID-19 vaccines . On 2 December, seven days after its final eight-week trial, the UK Medicines and Healthcare products Regulatory Agency (MHRA) became the first global medicines regulator in history to approve an mRNA vaccine, granting emergency authorization for Pfizer–BioNTech's BNT162b2 COVID-19 vaccine for widespread use. On 11 December, the FDA gave emergency use authorization for the Pfizer–BioNTech COVID-19 vaccine and a week later similar approval for the Moderna COVID-19 vaccine . Other mRNA vaccines continue to be developed, since the approval of the first mRNA vaccines. Moderna announced the development of mRNA vaccines for 15 diseases: Chikungunya virus , COVID-19, Crimean-Congo haemorrhagic fever , Dengue , Ebola virus disease , HIV , Malaria , Marburg virus disease , Lassa fever , Middle East respiratory syndrome coronavirus (MERS-CoV) , Nipah and henipaviral diseases, Rift Valley fever , Severe fever with Thrombocytopenia syndrome , Tuberculosis and Zika . The first successful transfection of designed mRNA packaged within a liposomal nanoparticle into a cell was published in 1989. "Naked" (or unprotected) lab-made mRNA was injected a year later into the muscle of mice. These studies were the first evidence that in vitro transcribed mRNA with a chosen gene was able to deliver the genetic information to produce a desired protein within living cell tissue and led to the concept proposal of messenger RNA vaccines. Liposome-encapsulated mRNA encoding a viral antigen was shown in 1993 to stimulate T cells in mice. The following year self-amplifying mRNA was developed by including both a viral antigen and replicase encoding gene. The method was used in mice to elicit both a humoral and cellular immune response against a viral pathogen. The next year mRNA encoding a tumor antigen was shown to elicit a similar immune response against cancer cells in mice. The first human clinical trial using ex vivo dendritic cells transfected with mRNA encoding tumor antigens ( therapeutic cancer mRNA vaccine ) was started in 2001. Four years later, the successful use of modified nucleosides as a method to transport mRNA inside cells without setting off the body's defense system was reported. Clinical trial results of an mRNA vaccine directly injected into the body against cancer cells were reported in 2008. BioNTech in 2008, and Moderna in 2010, were founded to develop mRNA biotechnologies. The US research agency DARPA launched at this time the biotechnology research program ADEPT to develop emerging technologies for the US military . The agency recognized the potential of nucleic acid technology for defense against pandemics and began to invest in the field. DARPA grants were seen as a vote of confidence that in turn encouraged other government agencies and private investors to invest in mRNA technology. DARPA awarded at the time a $25 million grant to Moderna. The first human clinical trials using an mRNA vaccine against an infectious agent ( rabies ) began in 2013. Over the next few years, clinical trials of mRNA vaccines for a number of other viruses were started. mRNA vaccines for human use were studied for infectious agents such as influenza , Zika virus , cytomegalovirus , and Chikungunya virus . The COVID-19 pandemic , and sequencing of the causative virus SARS-CoV-2 at the beginning of 2020, led to the rapid development of the first approved mRNA vaccines. BioNTech and Moderna in December of the same year obtained approval for their mRNA-based COVID-19 vaccines . On 2 December, seven days after its final eight-week trial, the UK Medicines and Healthcare products Regulatory Agency (MHRA) became the first global medicines regulator in history to approve an mRNA vaccine, granting emergency authorization for Pfizer–BioNTech's BNT162b2 COVID-19 vaccine for widespread use. On 11 December, the FDA gave emergency use authorization for the Pfizer–BioNTech COVID-19 vaccine and a week later similar approval for the Moderna COVID-19 vaccine . Other mRNA vaccines continue to be developed, since the approval of the first mRNA vaccines. Moderna announced the development of mRNA vaccines for 15 diseases: Chikungunya virus , COVID-19, Crimean-Congo haemorrhagic fever , Dengue , Ebola virus disease , HIV , Malaria , Marburg virus disease , Lassa fever , Middle East respiratory syndrome coronavirus (MERS-CoV) , Nipah and henipaviral diseases, Rift Valley fever , Severe fever with Thrombocytopenia syndrome , Tuberculosis and Zika . The goal of a vaccine is to stimulate the adaptive immune system to create antibodies that precisely target that particular pathogen . The markers on the pathogen that the antibodies target are called antigens . Traditional vaccines stimulate an antibody response by injecting either antigens , an attenuated (weakened) virus, an inactivated (dead) virus, or a recombinant antigen-encoding viral vector (harmless carrier virus with an antigen transgene ) into the body. These antigens and viruses are prepared and grown outside the body. In contrast, mRNA vaccines introduce a short-lived synthetically created fragment of the RNA sequence of a virus into the individual being vaccinated. These mRNA fragments are taken up by dendritic cells through phagocytosis . The dendritic cells use their internal machinery ( ribosomes ) to read the mRNA and produce the viral antigens that the mRNA encodes. The body degrades the mRNA fragments within a few days of introduction. Although non-immune cells can potentially also absorb vaccine mRNA, produce antigens, and display the antigens on their surfaces, dendritic cells absorb the mRNA globules much more readily. The mRNA fragments are translated in the cytoplasm and do not affect the body's genomic DNA, located separately in the cell nucleus . Once the viral antigens are produced by the host cell, the normal adaptive immune system processes are followed. Antigens are broken down by proteasomes . Class I and class II MHC molecules then attach to the antigen and transport it to the cellular membrane, "activating" the dendritic cell. Once activated, dendritic cells migrate to lymph nodes , where they present the antigen to T cells and B cells . This triggers the production of antibodies specifically targeted to the antigen, ultimately resulting in immunity . The central component of a mRNA vaccine is its mRNA construct. The in vitro transcribed mRNA is generated from an engineered plasmid DNA, which has an RNA polymerase promoter and sequence which corresponds to the mRNA construct. By combining T7 phage RNA polymerase and the plasmid DNA, the mRNA can be transcribed in the lab. Efficacy of the vaccine is dependent on the stability and structure of the designed mRNA. The in vitro transcribed mRNA has the same structural components as natural mRNA in eukaryotic cells . It has a 5' cap , a 5'-untranslated region (UTR) and 3'-UTR , an open reading frame (ORF), which encodes the relevant antigen, and a 3'-poly(A) tail . By modifying these different components of the synthetic mRNA, the stability and translational ability of the mRNA can be enhanced, and in turn, the efficacy of the vaccine improved. The mRNA can be improved by using synthetic 5'-cap analogues which enhance the stability and increase protein translation. Similarly, regulatory elements in the 5'-untranslated region and the 3'-untranslated region can be altered, and the length of the poly(A) tail optimized, to stabilize the mRNA and increase protein production. The mRNA nucleotides can be modified to both decrease innate immune activation and increase the mRNA's half-life in the host cell. The nucleic acid sequence and codon usage impacts protein translation. Enriching the sequence with guanine-cytosine content improves mRNA stability and half-life and, in turn, protein production. Replacing rare codons with synonymous codons frequently used by the host cell also enhances protein production. For a vaccine to be successful, sufficient mRNA must enter the host cell cytoplasm to stimulate production of the specific antigens. Entry of mRNA molecules, however, faces a number of difficulties. Not only are mRNA molecules too large to cross the cell membrane by simple diffusion , they are also negatively charged like the cell membrane, which causes a mutual electrostatic repulsion . Additionally, mRNA is easily degraded by RNAases in skin and blood. Various methods have been developed to overcome these delivery hurdles. The method of vaccine delivery can be broadly classified by whether mRNA transfer into cells occurs within ( in vivo ) or outside ( ex vivo ) the organism. Dendritic cells display antigens on their surfaces , leading to interactions with T cells to initiate an immune response. Dendritic cells can be collected from patients and programmed with the desired mRNA, then administered back into patients to create an immune response. The simplest way that ex vivo dendritic cells take up mRNA molecules is through endocytosis , a fairly inefficient pathway in the laboratory setting that can be significantly improved through electroporation . Since the discovery that the direct administration of in vitro transcribed mRNA leads to the expression of antigens in the body, in vivo approaches have been investigated. They offer some advantages over ex vivo methods, particularly by avoiding the cost of harvesting and adapting dendritic cells from patients and by imitating a regular infection. Different routes of injection , such as into the skin , blood , or muscles , result in varying levels of mRNA uptake, making the choice of administration route a critical aspect of in vivo delivery. One study showed, in comparing different routes, that lymph node injection leads to the largest T-cell response. Naked mRNA injection means that the delivery of the vaccine is only done in a buffer solution . This mode of mRNA uptake has been known since the 1990s. The first worldwide clinical studies used intradermal injections of naked mRNA for vaccination. A variety of methods have been used to deliver naked mRNA, such as subcutaneous, intravenous, and intratumoral injections. Although naked mRNA delivery causes an immune response, the effect is relatively weak, and after injection the mRNA is often rapidly degraded. Cationic polymers can be mixed with mRNA to generate protective coatings called polyplexes . These protect the recombinant mRNA from ribonucleases and assist its penetration in cells. Protamine is a natural cationic peptide and has been used to encapsulate mRNA for vaccination. [ non-primary source needed ] The first time the FDA approved the use of lipid nanoparticles as a drug delivery system was in 2018, when the agency approved the first siRNA drug, Onpattro . Encapsulating the mRNA molecule in lipid nanoparticles was a critical breakthrough for producing viable mRNA vaccines, solving a number of key technical barriers in delivering the mRNA molecule into the host cell. Research into using lipids to deliver siRNA to cells became a foundation for similar research into using lipids to deliver mRNA. However, new lipids had to be invented to encapsulate mRNA strands, which are much longer than siRNA strands. Principally, the lipid provides a layer of protection against degradation, allowing more robust translational output. In addition, the customization of the lipid's outer layer allows the targeting of desired cell types through ligand interactions. However, many studies have also highlighted the difficulty of studying this type of delivery, demonstrating that there is an inconsistency between in vivo and in vitro applications of nanoparticles in terms of cellular intake. The nanoparticles can be administered to the body and transported via multiple routes, such as intravenously or through the lymphatic system . One issue with lipid nanoparticles is that several of the breakthroughs leading to the practical use of that technology involve the use of microfluidics . Microfluidic reaction chambers are difficult to scale up, since the entire point of microfluidics is to exploit the microscale behaviors of liquids. The only way around this obstacle is to run an extensive number of microfluidic reaction chambers in parallel, a novel task requiring custom-built equipment. For COVID-19 mRNA vaccines, this was the main manufacturing bottleneck. Pfizer used such a parallel approach to solve the scaling problem. After verifying that impingement jet mixers could not be directly scaled up, Pfizer made about 100 of the little mixers (each about the size of a U.S. half-dollar coin ), connected them together with pumps and filters with a "maze of piping," and set up a computer system to regulate flow and pressure through the mixers. Another issue, with the large-scale use of this delivery method, is the availability of the novel lipids used to create lipid nanoparticles, especially ionizable cationic lipids. Before 2020, such lipids were manufactured in small quantities measured in grams or kilograms, and they were used for medical research and a handful of drugs for rare conditions. As the safety and efficacy of mRNA vaccines became clear in 2020, the few companies able to manufacture the requisite lipids were confronted with the challenge of scaling up production to respond to orders for several tons of lipids. In addition to non-viral delivery methods, RNA viruses have been engineered to achieve similar immunological responses. Typical RNA viruses used as vectors include retroviruses , lentiviruses , alphaviruses and rhabdoviruses , each of which can differ in structure and function. Clinical studies have utilized such viruses on a range of diseases in model animals such as mice , chicken and primates . Dendritic cells display antigens on their surfaces , leading to interactions with T cells to initiate an immune response. Dendritic cells can be collected from patients and programmed with the desired mRNA, then administered back into patients to create an immune response. The simplest way that ex vivo dendritic cells take up mRNA molecules is through endocytosis , a fairly inefficient pathway in the laboratory setting that can be significantly improved through electroporation . Since the discovery that the direct administration of in vitro transcribed mRNA leads to the expression of antigens in the body, in vivo approaches have been investigated. They offer some advantages over ex vivo methods, particularly by avoiding the cost of harvesting and adapting dendritic cells from patients and by imitating a regular infection. Different routes of injection , such as into the skin , blood , or muscles , result in varying levels of mRNA uptake, making the choice of administration route a critical aspect of in vivo delivery. One study showed, in comparing different routes, that lymph node injection leads to the largest T-cell response. Naked mRNA injection means that the delivery of the vaccine is only done in a buffer solution . This mode of mRNA uptake has been known since the 1990s. The first worldwide clinical studies used intradermal injections of naked mRNA for vaccination. A variety of methods have been used to deliver naked mRNA, such as subcutaneous, intravenous, and intratumoral injections. Although naked mRNA delivery causes an immune response, the effect is relatively weak, and after injection the mRNA is often rapidly degraded. Cationic polymers can be mixed with mRNA to generate protective coatings called polyplexes . These protect the recombinant mRNA from ribonucleases and assist its penetration in cells. Protamine is a natural cationic peptide and has been used to encapsulate mRNA for vaccination. [ non-primary source needed ] The first time the FDA approved the use of lipid nanoparticles as a drug delivery system was in 2018, when the agency approved the first siRNA drug, Onpattro . Encapsulating the mRNA molecule in lipid nanoparticles was a critical breakthrough for producing viable mRNA vaccines, solving a number of key technical barriers in delivering the mRNA molecule into the host cell. Research into using lipids to deliver siRNA to cells became a foundation for similar research into using lipids to deliver mRNA. However, new lipids had to be invented to encapsulate mRNA strands, which are much longer than siRNA strands. Principally, the lipid provides a layer of protection against degradation, allowing more robust translational output. In addition, the customization of the lipid's outer layer allows the targeting of desired cell types through ligand interactions. However, many studies have also highlighted the difficulty of studying this type of delivery, demonstrating that there is an inconsistency between in vivo and in vitro applications of nanoparticles in terms of cellular intake. The nanoparticles can be administered to the body and transported via multiple routes, such as intravenously or through the lymphatic system . One issue with lipid nanoparticles is that several of the breakthroughs leading to the practical use of that technology involve the use of microfluidics . Microfluidic reaction chambers are difficult to scale up, since the entire point of microfluidics is to exploit the microscale behaviors of liquids. The only way around this obstacle is to run an extensive number of microfluidic reaction chambers in parallel, a novel task requiring custom-built equipment. For COVID-19 mRNA vaccines, this was the main manufacturing bottleneck. Pfizer used such a parallel approach to solve the scaling problem. After verifying that impingement jet mixers could not be directly scaled up, Pfizer made about 100 of the little mixers (each about the size of a U.S. half-dollar coin ), connected them together with pumps and filters with a "maze of piping," and set up a computer system to regulate flow and pressure through the mixers. Another issue, with the large-scale use of this delivery method, is the availability of the novel lipids used to create lipid nanoparticles, especially ionizable cationic lipids. Before 2020, such lipids were manufactured in small quantities measured in grams or kilograms, and they were used for medical research and a handful of drugs for rare conditions. As the safety and efficacy of mRNA vaccines became clear in 2020, the few companies able to manufacture the requisite lipids were confronted with the challenge of scaling up production to respond to orders for several tons of lipids. In addition to non-viral delivery methods, RNA viruses have been engineered to achieve similar immunological responses. Typical RNA viruses used as vectors include retroviruses , lentiviruses , alphaviruses and rhabdoviruses , each of which can differ in structure and function. Clinical studies have utilized such viruses on a range of diseases in model animals such as mice , chicken and primates . Naked mRNA injection means that the delivery of the vaccine is only done in a buffer solution . This mode of mRNA uptake has been known since the 1990s. The first worldwide clinical studies used intradermal injections of naked mRNA for vaccination. A variety of methods have been used to deliver naked mRNA, such as subcutaneous, intravenous, and intratumoral injections. Although naked mRNA delivery causes an immune response, the effect is relatively weak, and after injection the mRNA is often rapidly degraded. Cationic polymers can be mixed with mRNA to generate protective coatings called polyplexes . These protect the recombinant mRNA from ribonucleases and assist its penetration in cells. Protamine is a natural cationic peptide and has been used to encapsulate mRNA for vaccination. [ non-primary source needed ] The first time the FDA approved the use of lipid nanoparticles as a drug delivery system was in 2018, when the agency approved the first siRNA drug, Onpattro . Encapsulating the mRNA molecule in lipid nanoparticles was a critical breakthrough for producing viable mRNA vaccines, solving a number of key technical barriers in delivering the mRNA molecule into the host cell. Research into using lipids to deliver siRNA to cells became a foundation for similar research into using lipids to deliver mRNA. However, new lipids had to be invented to encapsulate mRNA strands, which are much longer than siRNA strands. Principally, the lipid provides a layer of protection against degradation, allowing more robust translational output. In addition, the customization of the lipid's outer layer allows the targeting of desired cell types through ligand interactions. However, many studies have also highlighted the difficulty of studying this type of delivery, demonstrating that there is an inconsistency between in vivo and in vitro applications of nanoparticles in terms of cellular intake. The nanoparticles can be administered to the body and transported via multiple routes, such as intravenously or through the lymphatic system . One issue with lipid nanoparticles is that several of the breakthroughs leading to the practical use of that technology involve the use of microfluidics . Microfluidic reaction chambers are difficult to scale up, since the entire point of microfluidics is to exploit the microscale behaviors of liquids. The only way around this obstacle is to run an extensive number of microfluidic reaction chambers in parallel, a novel task requiring custom-built equipment. For COVID-19 mRNA vaccines, this was the main manufacturing bottleneck. Pfizer used such a parallel approach to solve the scaling problem. After verifying that impingement jet mixers could not be directly scaled up, Pfizer made about 100 of the little mixers (each about the size of a U.S. half-dollar coin ), connected them together with pumps and filters with a "maze of piping," and set up a computer system to regulate flow and pressure through the mixers. Another issue, with the large-scale use of this delivery method, is the availability of the novel lipids used to create lipid nanoparticles, especially ionizable cationic lipids. Before 2020, such lipids were manufactured in small quantities measured in grams or kilograms, and they were used for medical research and a handful of drugs for rare conditions. As the safety and efficacy of mRNA vaccines became clear in 2020, the few companies able to manufacture the requisite lipids were confronted with the challenge of scaling up production to respond to orders for several tons of lipids. In addition to non-viral delivery methods, RNA viruses have been engineered to achieve similar immunological responses. Typical RNA viruses used as vectors include retroviruses , lentiviruses , alphaviruses and rhabdoviruses , each of which can differ in structure and function. Clinical studies have utilized such viruses on a range of diseases in model animals such as mice , chicken and primates . mRNA vaccines offer specific advantages over traditional vaccines . Because mRNA vaccines are not constructed from an active pathogen (or even an inactivated pathogen), they are non-infectious. In contrast, traditional vaccines require the production of pathogens, which, if done at high volumes, could increase the risks of localized outbreaks of the virus at the production facility. Another biological advantage of mRNA vaccines is that since the antigens are produced inside the cell, they stimulate cellular immunity , as well as humoral immunity . mRNA vaccines have the production advantage that they can be designed swiftly. Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days. They can also be manufactured faster, more cheaply, and in a more standardized fashion (with fewer error rates in production), which can improve responsiveness to serious outbreaks. The Pfizer–BioNTech vaccine originally required 110 days to mass-produce (before Pfizer began to optimize the manufacturing process to only 60 days), which was substantially faster than traditional flu and polio vaccines. Within that larger timeframe, the actual production time is only about 22 days: two weeks for molecular cloning of DNA plasmids and purification of DNA, four days for DNA-to-RNA transcription and purification of mRNA, and four days to encapsulate mRNA in lipid nanoparticles followed by fill and finish . The majority of the days needed for each production run are allocated to rigorous quality control at each stage. In addition to sharing the advantages of theoretical DNA vaccines over established traditional vaccines , mRNA vaccines also have additional advantages over DNA vaccines. The mRNA is translated in the cytosol , so there is no need for the RNA to enter the cell nucleus , and the risk of being integrated into the host genome is averted. Modified nucleosides (for example, pseudouridines , 2'-O-methylated nucleosides) can be incorporated to mRNA to suppress immune response stimulation to avoid immediate degradation and produce a more persistent effect through enhanced translation capacity. The open reading frame (ORF) and untranslated regions (UTR) of mRNA can be optimized for different purposes (a process called sequence engineering of mRNA), for example through enriching the guanine-cytosine content or choosing specific UTRs known to increase translation. An additional ORF coding for a replication mechanism can be added to amplify antigen translation and therefore immune response, decreasing the amount of starting material needed. mRNA vaccines offer specific advantages over traditional vaccines . Because mRNA vaccines are not constructed from an active pathogen (or even an inactivated pathogen), they are non-infectious. In contrast, traditional vaccines require the production of pathogens, which, if done at high volumes, could increase the risks of localized outbreaks of the virus at the production facility. Another biological advantage of mRNA vaccines is that since the antigens are produced inside the cell, they stimulate cellular immunity , as well as humoral immunity . mRNA vaccines have the production advantage that they can be designed swiftly. Moderna designed their mRNA-1273 vaccine for COVID-19 in 2 days. They can also be manufactured faster, more cheaply, and in a more standardized fashion (with fewer error rates in production), which can improve responsiveness to serious outbreaks. The Pfizer–BioNTech vaccine originally required 110 days to mass-produce (before Pfizer began to optimize the manufacturing process to only 60 days), which was substantially faster than traditional flu and polio vaccines. Within that larger timeframe, the actual production time is only about 22 days: two weeks for molecular cloning of DNA plasmids and purification of DNA, four days for DNA-to-RNA transcription and purification of mRNA, and four days to encapsulate mRNA in lipid nanoparticles followed by fill and finish . The majority of the days needed for each production run are allocated to rigorous quality control at each stage. In addition to sharing the advantages of theoretical DNA vaccines over established traditional vaccines , mRNA vaccines also have additional advantages over DNA vaccines. The mRNA is translated in the cytosol , so there is no need for the RNA to enter the cell nucleus , and the risk of being integrated into the host genome is averted. Modified nucleosides (for example, pseudouridines , 2'-O-methylated nucleosides) can be incorporated to mRNA to suppress immune response stimulation to avoid immediate degradation and produce a more persistent effect through enhanced translation capacity. The open reading frame (ORF) and untranslated regions (UTR) of mRNA can be optimized for different purposes (a process called sequence engineering of mRNA), for example through enriching the guanine-cytosine content or choosing specific UTRs known to increase translation. An additional ORF coding for a replication mechanism can be added to amplify antigen translation and therefore immune response, decreasing the amount of starting material needed. Because mRNA is fragile, some vaccines must be kept at very low temperatures to avoid degrading and thus giving little effective immunity to the recipient. Pfizer–BioNTech's BNT162b2 mRNA vaccine has to be kept between −80 and −60 °C (−112 and −76 °F) . Moderna says their mRNA-1273 vaccine can be stored between −25 and −15 °C (−13 and 5 °F) , which is comparable to a home freezer, and that it remains stable between 2 and 8 °C (36 and 46 °F) for up to 30 days. In November 2020, Nature reported, "While it's possible that differences in LNP formulations or mRNA secondary structures could account for the thermostability differences [between Moderna and BioNtech], many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions." Several platforms are being studied that may allow storage at higher temperatures. Before 2020, no mRNA technology platform (drug or vaccine) had been authorized for use in humans, so there was a risk of unknown effects. The 2020 COVID-19 pandemic required faster production capability of mRNA vaccines, made them attractive to national health organisations, and led to debate about the type of initial authorization mRNA vaccines should get (including emergency use authorization or expanded access authorization ) after the eight-week period of post-final human trials. Reactogenicity is similar to that of conventional, non-RNA vaccines. However, those susceptible to an autoimmune response may have an adverse reaction to mRNA vaccines. The mRNA strands in the vaccine may elicit an unintended immune reaction – this entails the body believing itself to be sick, and the person feeling as if they are as a result. To minimize this, mRNA sequences in mRNA vaccines are designed to mimic those produced by host cells. Strong but transient reactogenic effects were reported in trials of novel COVID-19 mRNA vaccines; most people will not experience severe side effects which include fever and fatigue. Severe side effects are defined as those that prevent daily activity. Because mRNA is fragile, some vaccines must be kept at very low temperatures to avoid degrading and thus giving little effective immunity to the recipient. Pfizer–BioNTech's BNT162b2 mRNA vaccine has to be kept between −80 and −60 °C (−112 and −76 °F) . Moderna says their mRNA-1273 vaccine can be stored between −25 and −15 °C (−13 and 5 °F) , which is comparable to a home freezer, and that it remains stable between 2 and 8 °C (36 and 46 °F) for up to 30 days. In November 2020, Nature reported, "While it's possible that differences in LNP formulations or mRNA secondary structures could account for the thermostability differences [between Moderna and BioNtech], many experts suspect both vaccine products will ultimately prove to have similar storage requirements and shelf lives under various temperature conditions." Several platforms are being studied that may allow storage at higher temperatures. Before 2020, no mRNA technology platform (drug or vaccine) had been authorized for use in humans, so there was a risk of unknown effects. The 2020 COVID-19 pandemic required faster production capability of mRNA vaccines, made them attractive to national health organisations, and led to debate about the type of initial authorization mRNA vaccines should get (including emergency use authorization or expanded access authorization ) after the eight-week period of post-final human trials. Reactogenicity is similar to that of conventional, non-RNA vaccines. However, those susceptible to an autoimmune response may have an adverse reaction to mRNA vaccines. The mRNA strands in the vaccine may elicit an unintended immune reaction – this entails the body believing itself to be sick, and the person feeling as if they are as a result. To minimize this, mRNA sequences in mRNA vaccines are designed to mimic those produced by host cells. Strong but transient reactogenic effects were reported in trials of novel COVID-19 mRNA vaccines; most people will not experience severe side effects which include fever and fatigue. Severe side effects are defined as those that prevent daily activity. The COVID-19 mRNA vaccines from Moderna and Pfizer–BioNTech have efficacy rates of 90 to 95 percent [ citation needed ] . Prior mRNA, drug trials on pathogens other than COVID-19 were not effective and had to be abandoned in the early phases of trials. The reason for the efficacy of the new mRNA vaccines is not clear. Physician-scientist Margaret Liu stated that the efficacy of the new COVID-19 mRNA vaccines could be due to the "sheer volume of resources" that went into development, or that the vaccines might be "triggering a nonspecific inflammatory response to the mRNA that could be heightening its specific immune response, given that the modified nucleoside technique reduced inflammation but hasn't eliminated it completely", and that "this may also explain the intense reactions such as aches and fevers reported in some recipients of the mRNA SARS-CoV-2 vaccines". These reactions though severe were transient and another view is that they were believed to be a reaction to the lipid drug delivery molecules. There is misinformation implying that mRNA vaccines could alter DNA in the nucleus. mRNA in the cytosol is very rapidly degraded before it would have time to gain entry into the cell nucleus. In fact, mRNA vaccines must be stored at very low temperature and free from RNAses to prevent mRNA degradation. Retrovirus can be single-stranded RNA (just as many SARS-CoV-2 vaccines are single-stranded RNA) which enters the cell nucleus and uses reverse transcriptase to make DNA from the RNA in the cell nucleus. A retrovirus has mechanisms to be imported into the nucleus, but other mRNA (such as the vaccine) lack these mechanisms. Once inside the nucleus, creation of DNA from RNA cannot occur without a reverse transcriptase and appropriate primers , which both accompany a retrovirus, but which would not be present for other exogenous mRNA (such as a vaccine) even if it could enter the nucleus. mRNA vaccines use either non-amplifying (conventional) mRNA or self-amplifying mRNA. Pfizer–BioNTech and Moderna vaccines use non-amplifying mRNA. Both mRNA types continue to be investigated as vaccine methods against other potential pathogens and cancer. The initial mRNA vaccines use a non-amplifying mRNA construct. Non-amplifying mRNA has only one open reading frame that codes for the antigen of interest. The total amount of mRNA available to the cell is equal to the amount delivered by the vaccine. Dosage strength is limited by the amount of mRNA that can be delivered by the vaccine. Non-amplifying vaccines replace uridine with N1-Methylpseudouridine in an attempt to reduce toxicity. Self-amplifying mRNA (saRNA) vaccines replicate their mRNA after transfection. Self-amplifying mRNA has two open reading frames . The first frame, like conventional mRNA, codes for the antigen of interest. The second frame codes for an RNA-dependent RNA polymerase (and its helper proteins) which replicates the mRNA construct in the cell. This allows smaller vaccine doses. The mechanisms and consequently the evaluation of self-amplifying mRNA may be different, as self-amplifying mRNA is a much bigger molecule. SaRNA vaccines being researched include a malaria vaccine . Gritstone bio started in 2021 a phase 1 trial of an saRNA COVID-19 vaccine, used as a booster vaccine . The vaccine is designed to target both the spike protein of the SARS‑CoV‑2 virus, and viral proteins that may be less prone to genetic variation, to provide greater protection against SARS‑CoV‑2 variants. saRNA vaccines must use uridine, which is required for reproduction to occur. The initial mRNA vaccines use a non-amplifying mRNA construct. Non-amplifying mRNA has only one open reading frame that codes for the antigen of interest. The total amount of mRNA available to the cell is equal to the amount delivered by the vaccine. Dosage strength is limited by the amount of mRNA that can be delivered by the vaccine. Non-amplifying vaccines replace uridine with N1-Methylpseudouridine in an attempt to reduce toxicity. Self-amplifying mRNA (saRNA) vaccines replicate their mRNA after transfection. Self-amplifying mRNA has two open reading frames . The first frame, like conventional mRNA, codes for the antigen of interest. The second frame codes for an RNA-dependent RNA polymerase (and its helper proteins) which replicates the mRNA construct in the cell. This allows smaller vaccine doses. The mechanisms and consequently the evaluation of self-amplifying mRNA may be different, as self-amplifying mRNA is a much bigger molecule. SaRNA vaccines being researched include a malaria vaccine . Gritstone bio started in 2021 a phase 1 trial of an saRNA COVID-19 vaccine, used as a booster vaccine . The vaccine is designed to target both the spike protein of the SARS‑CoV‑2 virus, and viral proteins that may be less prone to genetic variation, to provide greater protection against SARS‑CoV‑2 variants. saRNA vaccines must use uridine, which is required for reproduction to occur.

Wiki

Chikungunya

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

Rabies in Haiti

Rabies is a viral disease that exists in Haiti and throughout the world. It often causes fatal inflammation of the brain in humans and other mammals , such as dogs and mongooses in Haiti. The term "rabies" is derived from a Latin word that means "to rage"; rabid animals sometimes appear to be angry. Early symptoms can include fever and tingling at the site of exposure, followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness . Once symptoms appear, death is nearly always the outcome. The time period between contracting the disease and showing symptoms is usually one to three months; however, this time period can vary from less than a week to more than a year. The time between contraction and the onset of symptoms is dependent on the distance the virus must travel to reach the central nervous system . Haiti is one of five remaining countries in the Americas where canine rabies is still a problem, and it has the highest rate of human rabies deaths in the Western Hemisphere. Following the 2010 earthquake , rabies caused an estimated two deaths per week. Only a small number of these rabies deaths were reported to health authorities due to the impact of the earthquake, limitations in testing capacity, and lack of awareness and education about the disease among Haitians. Globally, 59,000 people die from rabies each year. This is the equivalent of one person dying every nine minutes, with half of the people who die from rabies being under the age of 15. The Pan American Health Organization (PAHO) and the Pan American Center of foot-and-mouth disease (PANAFTOSA) led a mission to eliminate dog-mediated rabies in the American region by 2015. These organizations are cognizant of the regional control of rabies. The PAHO and PANAFTOSA visited Haiti in early December, 2013, and the objectives of the mission were to assess the status of Haiti's rabies program as delivered by the Haitian Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Ministry of Health (MSPP). The mission was to seek opportunities for collaboration between Haiti, Brazil, and the Centers for Disease Control and Prevention (CDC) in Haiti. Even in 2017, rabies in Haiti is still identified as a national problem, even with PEP proposed. In Haiti, few cases of human rabies are reported to health authorities. In 2016, a report of a woman who had been exposed to rabies three months prior and was showing symptoms went to the hospital where no treatment was administered to her. Even after being reported to both the CDC and the national Department of Epidemiology and Laboratory Research (DELR), as required by Haiti's surveillance program, the woman died. This goes to show the lack of communication and effectiveness in caring for human subjects in Haiti, and the continued focus is on eliminating dog-mediated rabies altogether. Human diploid cell culture rabies vaccine ( HDCV ) and purified chick embryo cell culture rabies vaccine ( PCEC ) are used to treat post-exposure immunization against a human rabies infection. Recommendations for treatment are given by governmental health care organizations and in health literature. Health care providers are encouraged to administer a regimen of four 1-mL doses of HDCV or PCEC vaccines. According to the CDC, these injections should be administered intramuscularly to persons who have not yet been vaccinated for rabies. For those who are unvaccinated, the first of four doses is administered immediately after exposure to the rabies virus. Additional doses are given three, seven, and fourteen days after the first vaccination. Exposure usually means a bite from a rabid animal. At an individual patient level, post-exposure prophylaxis (PEP) consists of local treatment of the wound, vaccination, and administration of immunoglobulin, if necessary . At the program level, several components are critical, including: adequate and prompt recognition of the need for PEP by the public, if exposed, and by health officials, prompt and sufficient availability of high-quality PEP, and adequate follow-up of PEP use. Health officials' awareness of the need for PEP after a dog bite can only be achieved if the exposure is attended to immediately and communicated effectively. Dog vaccination is most effective for controlling dog-mediated rabies. This can be seen throughout the region of the Americas where medical authorities have achieved rabies control. In Haiti, the United States Centers for Disease Control (CDC) is mainly focusing on dog-mediated rabies. Specifically in collaboration with the NGO Christian Veterinary Mission, the CDC has trained, to date, more than 20 MARNDR laboratory personnel in rabies diagnostic methods (Direct Fluorescent Antibody [DFA] and Direct Rapid Immunohistochemistry Test [dRIT]). The organizations have also improved a diagnostic laboratory in Port-au-Prince by providing it with advanced equipment. The surveillance system is a bite-reporting model where the public and medical providers report bite events to rabies control officers. In addition, more than 30 field veterinary and health agents were trained in rabies surveillance, in support of this effort. In 2011, the CDC along with MARNDR initiated a five-year rabies infrastructure improvement program that focused on surveillance, diagnostics, and education. The MSPP also helped out by improving public education on rabies. Because Haiti has a gross national income per capita of US$1,035, it is the only country in the American region that is part of the group of low-income countries. The World Bank has classified 33 other low-income countries in Africa and Asia, where dog-mediated rabies is a major problem and results in thousands of deaths annually. The persistence of dog rabies is connected to limited resources and weak governance. In conducting a rabies assessment, rabies control officers try to locate the offending animal. Animals that have bitten a victim are either euthanized and tested or quarantined for 14 days while remaining in their owner's residence. In addition, animals who show signs of rabies are tested, regardless of human exposure. This surveillance program is restricted to two of the ten geographical departments of the country (West and Artibonite) for security reasons. The area includes approximately 50 percent of the Haitian population. The CDC and the NGO Christian Veterinary Mission support the mission by maintaining four Haitian staff in the West Department and three in the Artibonite Department, respectively. Results of this mission showed the level of under-reporting of canine rabies. Specifically, six cases of rabid dogs in early December, 2012, were reported for the country. During the first nine months of the surveillance mission, 42 rabid dogs were identified in just three communities in Port-au-Prince during the first nine months in 2012. That being said, no laboratory-based surveillance exists for the human population that is exposed to rabies and all diagnoses are based on clinical history. This is because of the lack of laboratory facilities, making it difficult to identify evidence for the virus in humans and shed light on the disease as a whole for them, in Haiti. There are insufficient numbers of pathologists to collect samples for human rabies, as well. There do exist other methods for viral antigen detection that may merit study. In 2013, the CDC and its partners began an animal rabies surveillance program in several regions of Haiti and saw an 18-fold rise in detection of rabid animals. In 2015, the CDC evaluated Haiti's canine rabies vaccination program and found that only 45 percent of dogs were vaccinated, far short of the 70 percent needed to stop the spread of rabies in the dog population. In addition, the researchers found that Haiti had nearly 1,000,000 dogs, twice as many as previously thought. The CDC and its partners had already begun a dog vaccination trial in evaluating the best vaccination methods for dogs in Haiti. As a part of this effort, they vaccinated 3,000 dogs in just four days during the summer of 2016 and planned to vaccinate a total of 8,000 dogs as part of this campaign. In Haiti, the control of dog rabies is led by the MARNDR while the MSPP manages health-care and rabies prevention in the human population. The separation of these ministries makes it easier for responsibilities to be divided among them. Communication about finding the source of exposure and implementing control methods to prevent further cross-species transmission is also more effective. This task is difficult enough within departments of the same ministry, (e.g., health care and epidemiology), which can be seen in experiences elsewhere. This is why a comprehensive evaluation of Haiti's rabies program should heavily consider the costs and benefits of this separation of responsibilities between the two ministries early on. Despite a planned mass vaccination for dogs in 2013, no campaign was actually conducted. Authorities in Haiti relied on funds donated by the World Bank for the purchase of approximately 500,000 doses of inactivated, injectable vaccine (IMRAB by Merial). Although the funds were awarded in April 2013, the vaccine itself did not arrive until 2014 when the dog vaccination finally went underway in September 2014. The process as a whole was expected to terminate in January 2015. The lack of manpower needed to deliver faster implementation made it impossible for the campaign to be completed in less than four months. Another challenge presented is vaccination failure, which usually leads to recurrent rabies in dogs and inconsistent control of the disease. The failures that disrupt annual campaigns or have insufficient coverage, for example, are seen as the main cause for this problem. Another factor is that in Haiti, dog vaccinations have been inconsistently applied. Back in 2012 when the last mass vaccination was led by the MARNDR, approximately 400,000 dogs were vaccinated. With this in mind, considering a current human population of approximately 10,000,000, a relation of one dog per ten people, and aiming to attain 70 percent of vaccine coverage, 700,000 dogs would have to be vaccinated. Assessing the effectiveness of this vaccination campaign is difficult because the dog population figures are unreliable (estimates range from 800,000 to 1,200,000 dogs), and though the overall success seems to be limited. The number of rabid dogs detected by the MARNDR, MSPP, and CDC is a huge risk to people and is not accurately reflected in their surveillance figures. Although international support is common in both technical help and donations, it is not comprehensive. In addition, the MARNDR, MSPP, and other actors do not communicate effectively because of human resource limitations. That being said, the 2015 elimination goal in the region was compromised and control of the disease could not yet be achieved, despite the efforts of resolute national officials. In conclusion, rabies in the dog population is still a problem and major threat to the Haitian population.

Wiki

Chikungunya

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

Caries vaccine

A caries vaccine is a vaccine to prevent and protect against tooth decay . Streptococcus mutans ( S. mutans ) has been identified as the major etiological agent of human dental caries. The development of a vaccine for tooth decay has been under investigation since the 1970s. In 1972, a caries vaccine was said to be in animal testing in England, and that it would have begun human testing soon. However, intrinsic difficulties in developing it, coupled with lack of strong economic interests, are the reasons why still no such vaccine is commercially available today. [ citation needed ] Several types of vaccines are being developed at research centres, with some kind of caries vaccines being considered to diminish or prevent dental caries' impact on young people. Early attempts followed a traditional approach to vaccination where normal S. mutans was introduced to promote a reaction from the immune system, stimulating antibody production. [ non-primary source needed ] Planet Biotechnology developed a monoclonal antibody against S. mutans , branded CaroRx, produced with transgenic tobacco plants. It is a therapeutic vaccine , applied once every several months. Phase II clinical trials were discontinued in 2016. [ citation needed ] The International Association for Dental Research and American Association for Dental Research announced a study performed by the Chinese Academy of Sciences which looked at using an inhaled vaccine that uses a protein filament as a delivery vehicle. Trials performed in rats showed an increase in antibody response along with a decrease in the amount of Streptococcus mutans adhering to teeth, leading to significantly fewer cavities observed among the test population. [ non-primary source needed ]On a different line of research, Jeffrey Hillman from the University of Florida developed a genetically modified strain of Streptococcus mutans called BCS3-L1, that is incapable of producing lactic acid – the acid that dissolves tooth enamel – and aggressively replaces native flora. In laboratory tests, rats who were given BCS3-L1 were conferred with a lifetime of protection against S. mutans . [ non-primary source needed ] BCS3-L1 colonizes the mouth and produces a small amount of a lantibiotic , called MU1140, which allows it to out-compete S. mutans . Hillman suggested that treatment with BCS3-L1 in humans could also provide a lifetime of protection, or, at worst, require occasional re-applications. He stated that the treatment would be available in dentists' offices and "will probably cost less than $100." The product was being developed by Oragenics, but was shelved in 2014, citing regulatory concerns and patent issues. [ non-primary source needed ] In 2016, Oragenics received a 17-year patent for the product. In 2023, the startup Lumina Probiotic began offering BCS3-L1 application in Próspera, Honduras. [ citation needed ] On rare occasions the native S. mutans strain escapes into the blood, potentially causing dangerous heart infections. It is unclear how likely BCS3-L1 is to do the same. Another approach is being pursued by BASF , focused on replacing native lactobacillus flora with a variety dubbed L. anti-caries , which prevents S. mutans from binding to enamel. However, it is not a long-term vaccination in that no attempt is being made to have a self-sustaining population of L. anti-caries . The intent is that the L. anti-caries population would be frequently replenished through use of a chewing gum containing the organism. [ citation needed ] The University of Leeds has also begun researching a recently discovered peptide known as P11-4 . When applied to a cavity and coming in contact with saliva, this peptide assembles itself in a fibrous matrix or scaffold, attracting calcium and thereby allowing the tooth to regenerate. The Swiss-based company Credentis has licensed the peptide and launched a product called Curodont Repair in 2013. Recent studies show a positive clinical effect. [ non-primary source needed ]DNA vaccine approaches for dental cavities have had a history of success in animal models. Dental cavity vaccines directed to key components of S. mutans colonization and enhanced by safe and effective adjuvants and optimal delivery vehicles, are likely to be forthcoming. Some believe that the rational target for developing an anti-caries vaccine is a protein antigen, which has adherent functional and important immunogenic regions. [ clarification needed ] [ non-primary source needed ]The use of Enterococcus faecalis bacteriophages as a form of treatment for caries has been considered, as they are capable of maintaining persistent stability in human saliva. [ non-primary source needed ]

Wiki

Chikungunya

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

Hantavirus hemorrhagic fever with renal syndrome

Hantavirus hemorrhagic fever with renal syndrome ( HFRS ) is a group of clinically similar illnesses caused by species of hantaviruses . It is also known as Korean hemorrhagic fever and epidemic hemorrhagic fever . It is found in Europe, Asia, and Africa. The species that cause HFRS include Hantaan orthohantavirus , Dobrava-Belgrade orthohantavirus , Saaremaa virus , Seoul orthohantavirus , Puumala orthohantavirus and other orthohantaviruses. Of these species, Hantaan River virus and Dobrava-Belgrade virus cause the most severe form of the syndrome and have the highest morbidity rates. When caused by the Puumala virus, it is also called nephropathia epidemica . This infection is known as sorkfeber (vole fever) in Swedish, myyräkuume (vole fever) in Finnish, and musepest (mouse plague) in Norwegian. Both HFRS and hantavirus pulmonary syndrome (HPS) are caused by hantaviruses, specifically when humans inhale aerosolized excrements of infected rodents. Both diseases appear to be immunopathologic , and inflammatory mediators are important in causing the clinical manifestations. Symptoms of HFRS usually develop within one to two weeks after exposure to infectious material, but in rare cases, they may take up to eight weeks to develop. In Nephropathia epidemica, the incubation period is three weeks. Initial symptoms begin suddenly and include intense headaches, back and abdominal pain, fever, chills, nausea, and blurred vision. Individuals may have flushing of the face, inflammation or redness of the eyes, or a rash. Later symptoms can include low blood pressure, acute shock, vascular leakage, and acute kidney failure, which can cause severe fluid overload. The severity of the disease varies depending upon the virus causing the infection. Hantaan and Dobrava virus infections usually cause severe symptoms, while Seoul, Saaremaa, and Puumala virus infections are usually more moderate. Complete recovery can take weeks or months. The course of the illness can be split into five phases: This syndrome can also be fatal. In some cases, it has been known to cause permanent renal failure. Hantaviruses infect various rodents, generally without causing disease. Transmission by aerosolized rodent excreta still remains the only known way the virus is transmitted to humans. In general, droplet and/or fomite transfer has not been shown in the hantaviruses in either the pulmonary or hemorrhagic forms. For Nephropathia epidemica, the bank vole is the reservoir for the virus, which humans contract through inhalation of aerosolised vole droppings. HFRS is difficult to diagnose on clinical grounds alone and serological evidence is often needed. A fourfold rise in IgG antibody titer in a one-week interval and the presence of the IgM type of antibodies against hantaviruses are good evidence for an acute hantavirus infection. HFRS should be suspected in patients with acute febrile flu-like illness, kidney failure of unknown origin and sometimes liver dysfunction. Rodent control in and around the home remains the primary prevention strategy, as well as eliminating contact with rodents in the workplace and campsite. Closed storage sheds and cabins are often ideal sites for rodent infestations. Airing out of such spaces prior to use is recommended. Avoid direct contact with rodent droppings and wear a mask to avoid inhalation of aerosolized rodent secretions. There is no cure for HFRS. Treatment involves supportive therapy including renal dialysis. Treatment with ribavirin in China and Korea, administered within seven days of onset of fever, resulted in a reduced mortality as well as shortened course of illness. HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas. The geography is directly related to the indigenous rodent hosts and the viruses that coevolved with them. Although fatal in a small percentage of cases, nephropathia epidemica is generally milder than the HFRS that is caused by hantaviruses in other parts of the world. HFRS was the subject of an episode of the television series M*A*S*H. In season 8, episode 9 the 4077th dealt with a condition, with similar symptoms to HFRS, called "Korean Hemorrhagic Fever".

Wiki

Chikungunya

https://api.wikimedia.org/core/v1/wikipedia/en/page/Kaposi's_sarcoma/html

Kaposi's sarcoma

Kaposi's sarcoma ( KS ) is a type of cancer that can form masses in the skin , in lymph nodes , in the mouth, or in other organs . The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limited area, or may be widespread. Depending on the sub-type of disease and level of immune suppression, KS may worsen either gradually or quickly. Except for Classical KS where there is generally no immune suppression, KS is caused by a combination of immune suppression (such as due to HIV/AIDS ) and infection by Human herpesvirus 8 (HHV8 – also called KS-associated herpesvirus (KSHV)). Classic, endemic, immunosuppression therapy-related (also known as iatrogenic), and epidemic (also known as AIDS-related) sub-types are all described. Classic KS tends to affect older men in regions where KSHV is highly prevalent (Mediterranean, Eastern Europe, Middle East), is usually slow-growing, and most often affects only the legs. Endemic KS is most common in Sub-Saharan Africa and is more aggressive in children, while older adults present similarly to classic KS. Immunosuppression therapy-related KS generally occurs in people following organ transplantation and mostly affects the skin. Epidemic KS occurs in people with AIDS and many parts of the body can be affected. KS is diagnosed by tissue biopsy , while the extent of disease may be determined by medical imaging . Treatment is based on the sub-type, whether the condition is localized or widespread, and the person's immune function. Localized skin lesions may be treated by surgery, injections of chemotherapy into the lesion, or radiation therapy . Widespread disease may be treated with chemotherapy or biologic therapy . In those with HIV/AIDS, highly active antiretroviral therapy (HAART) prevents and often treats KS. In certain cases the addition of chemotherapy may be required. With widespread disease, death may occur. The condition is relatively common in people with HIV/AIDS and following organ transplant. Over 35% of people with AIDS may be affected. KS was first described by Moritz Kaposi in 1872. It became more widely known as one of the AIDS-defining illnesses in the 1980s. KSHV was discovered as a causative agent in 1994. KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular . [ citation needed ] They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract and respiratory tract . Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity . The lesions are painless, but become cosmetically disfiguring or interruptive to organs. Commonly affected areas include the lower limbs , back, face, mouth, and genitalia . The lesions are usually as described above, but may occasionally be plaque -like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions . Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Kaposi's sarcoma skin lesions may be psychologically distressing. The mouth is involved in about 30% of cases, and is the initial site in 15% of AIDS-related KS. In the mouth, the hard palate is most frequently affected, followed by the gums . Lesions in the mouth may be easily damaged by chewing and bleed or develop secondary infection, and even interfere with eating or speaking. [ citation needed ] Involvement can be common in those with transplant-related or AIDS-related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea , bleeding (either vomiting blood or passing it with bowel movements), malabsorption , or intestinal obstruction . Involvement of the airway can present with shortness of breath, fever , cough , coughing up blood or chest pain, or as an incidental finding on chest x-ray . The diagnosis is usually confirmed by bronchoscopy , when the lesions are directly seen and often biopsied. Kaposi's sarcoma of the lung has a poor prognosis. [ citation needed ]Commonly affected areas include the lower limbs , back, face, mouth, and genitalia . The lesions are usually as described above, but may occasionally be plaque -like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions . Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Kaposi's sarcoma skin lesions may be psychologically distressing. The mouth is involved in about 30% of cases, and is the initial site in 15% of AIDS-related KS. In the mouth, the hard palate is most frequently affected, followed by the gums . Lesions in the mouth may be easily damaged by chewing and bleed or develop secondary infection, and even interfere with eating or speaking. [ citation needed ]Involvement can be common in those with transplant-related or AIDS-related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea , bleeding (either vomiting blood or passing it with bowel movements), malabsorption , or intestinal obstruction . Involvement of the airway can present with shortness of breath, fever , cough , coughing up blood or chest pain, or as an incidental finding on chest x-ray . The diagnosis is usually confirmed by bronchoscopy , when the lesions are directly seen and often biopsied. Kaposi's sarcoma of the lung has a poor prognosis. [ citation needed ]Kaposi's sarcoma-associated herpesvirus (KSHV), also called HHV-8, is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic . KSHV encodes oncogenes , microRNAs and circular RNAs that promote cancer cell proliferation and escape from the immune system. In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown. [ citation needed ] KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission. [ citation needed ]In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown. [ citation needed ] KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission. [ citation needed ]Despite its name, in general it is not considered a true sarcoma , which is a tumor arising from mesenchymal tissue . The histogenesis of KS remains controversial. KS may arise as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance. KSHV proteins are uniformly detected in KS cancer cells. [ citation needed ] KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells . The most typical feature of Kaposi sarcoma is the presence of spindle cells forming slits containing red blood cells. Mitotic activity is only moderate and pleomorphism is usually absent. The tumor is highly vascular , containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain. Variously sized PAS positive hyaline bodies are often seen in the cytoplasm or sometimes extracellularly. [ citation needed ] The spindle cells of Kaposi sarcoma differentiate toward endothelial cells , probably of lymph vessel rather than blood vessel origin. The consistent immunoreactivity for podoplanin supports the lymphatic nature of the lesion. [ citation needed ]Although KS may be suspected from the appearance of lesions and the patient's risk factors, a definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis. [ citation needed ] In differential diagnosis, arteriovenous malformations , pyogenic granuloma and other vascular proliferations can be microscopically confused with KS. Source: Naevus Histiocytoma Cryptococcosis Histoplasmosis Leishmaniasis Pneumocystis lesions Dermatophytosis Angioma Bacillary angiomatosis Pyogenic granuloma Melanoma HHV-8 is responsible for all varieties of KS. Since Moritz Kaposi first described the cancer, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses. : 599 All of the forms are infected with KSHV and are different manifestations of the same disease but have differences in clinical aggressiveness, prognosis, and treatment.Source: Naevus Histiocytoma Cryptococcosis Histoplasmosis Leishmaniasis Pneumocystis lesions Dermatophytosis Angioma Bacillary angiomatosis Pyogenic granuloma MelanomaHHV-8 is responsible for all varieties of KS. Since Moritz Kaposi first described the cancer, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses. : 599 All of the forms are infected with KSHV and are different manifestations of the same disease but have differences in clinical aggressiveness, prognosis, and treatment.Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting the infection to their sexual partner, or whether an organ is infected before transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant. [ citation needed ]Kaposi sarcoma is not curable, but it can often be treatable for many years. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). Therefore, HAART is considered the cornerstone of therapy in AIDS-associated Kaposi sarcoma. However, in a certain percentage [ vague ] of such people, Kaposi sarcoma may recur after many years on HAART, especially if HIV is not completely suppressed. People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery . Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually. Limited basic and clinical evidence suggest that topical beta-blockers , such as timolol , may induce regression of localized lesions in classic as well as HIV-associated Kaposi sarcoma. In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. In general, more widespread disease, or disease affecting internal organs, is treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as liposomal doxorubicin or daunorubicin ), thalidomide , or paclitaxel . Alitretinoin , applied to the lesion, may be used when the lesion is not getting better with standard treatment of HIV/AIDS and chemotherapy or radiation therapy cannot be used. With the decrease in the death rate among people with HIV/AIDS receiving new treatments in the 1990s, the rates and severity of epidemic KS also decreased. However, the number of people living with HIV/AIDS is increasing in the United States, and it is possible that the number of people with AIDS-associated Kaposi sarcoma will again rise as these people live longer with HIV infection. [ citation needed ]Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi sarcoma entered the awareness of the general public with the release of the film Philadelphia , in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. By the time KS lesions appear, likely, the immune system has already been severely weakened. [ citation needed ] It has been reported that only 6% of men who have sex with men are aware that KS is caused by a virus different from HIV. Thus, there is little community effort to prevent KSHV infection. Likewise, no systematic screening of organ donations is in place. In people with AIDS, Kaposi sarcoma is considered an opportunistic infection , a disease that can gain a foothold in the body because the immune system has been weakened. With the rise of HIV/AIDS in Africa , where KSHV is widespread, KS has become the most frequently reported cancer in some countries.

Wiki

Chikungunya

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

Viral encephalitis

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis , by a virus . The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior. Viral encephalitis can be diagnosed based on the individual's symptoms, personal history, such as travel history, and different clinical tests such as histology , medical imaging , and lumbar punctures . A differential diagnosis can also be done to rule out other causes of the encephalitis. Many encephalitic viruses often have characteristic symptoms of infection, helping to aid diagnosis. Treatment is usually supportive in nature while also providing antiviral drug therapy. The primary exception to this is herpes simplex encephalitis, which is treatable with acyclovir . Prognosis is good for most individuals who are infected by an encephalitic virus but is poor among those who develop severe symptoms, including viral encephalitis. Long-term complications of viral encephalitis typically relate to neurological damage, such as experiencing seizures , memory loss, and intellectual impairment. Encephalitic viruses are typically transmitted either from person-to-person or are arthropod -borne viruses, called arboviruses . The young and the elderly are at the highest risk of viral encephalitis. Many cases of viral encephalitis are not identified either because of lack of testing or mild illness, and serological surveys indicate that asymptomatic infections are common. Various ways of preventing viral encephalitis exist, such as vaccines that are either in standard vaccination programs or which are recommended when living in or visiting certain regions, and various measures aimed at preventing mosquito, sandfly, and tick bites in order to prevent arbovirus infection.Many viruses are capable of causing encephalitis during infection, including: Encephalitic viruses vary in their manner of transmission. Some are transmitted from person-to-person, whereas others are transmitted by animals, especially bites from arthropods such as mosquitos, sandflies, and ticks, such viruses being called arboviruses . An example of person-to-person transmission is the herpes simplex virus, which is transmitted by means of intimate physical contact. An example of arboviral transmission is the West Nile virus, which usually is incidentally transmitted to people from the bites of Culex mosquitos, especially Culex pipiens . Encephalitic viruses vary in their manner of transmission. Some are transmitted from person-to-person, whereas others are transmitted by animals, especially bites from arthropods such as mosquitos, sandflies, and ticks, such viruses being called arboviruses . An example of person-to-person transmission is the herpes simplex virus, which is transmitted by means of intimate physical contact. An example of arboviral transmission is the West Nile virus, which usually is incidentally transmitted to people from the bites of Culex mosquitos, especially Culex pipiens . Viruses that cause viral encephalitis first infect the body and replicate outside of the central nervous system (CNS). Thereafter, most reach the spinal cord and brain via the circulatory system. Exceptions to this include herpesviruses and the rabies virus, which travel from nerve endings to the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural cell function, including causing fluid buildup in the brain , vascular congestion , and bleeding . Widespread presence of white blood cells and microglia in the CNS is common as a response to CNS infection. For some forms of viral encephalitis, such as Eastern equine encephalitis and Japanese encephalitis , there may be a significant amount of necrosis of nerve cells. Following encephalitis caused by arboviruses, calcification may occur in the CNS, especially among children. Herpes simplex encephalitis tends to produce necrotic lesions in the CNS. If viral encephalitis is suspected, then questions can be asked about the individual's history and physical examination can be performed. Important aspects of one's history include immune status, exposure to animals, including insects, travel history, vaccination history, geography, and time of year. Symptoms usually occur acutely, and the most common symptoms of infection are fever, headache, altered mental status, sensitivity to light , stiff neck and back, vomiting, confusion, and, in severe cases, seizures , paralysis, and coma. Neuropsychiatric features such as behavioral changes, hallucinations, or cognitive decline are frequent. Severe symptoms are most common among infants and the elderly. Most infections are asymptomatic, lacking symptoms, whereas most symptomatic cases are mild illnesses. Virus-specific symptoms may also exist or tests may indicate one virus. Specific examples include: The brain histology of viral encephalitis shows dead neurons with nuclear dissolution and elevated eosinophil count, called hypereosinophilia , within cells' cytoplasm when viewed with an optical microscope . Because encephalitis is an inflammatory response, inflammatory cells situated near blood vessels, such as microglia , macrophages , and lymphocytes , are visible. Virions within neurons are visible via electron microscopes . Neuroimaging and lumbar puncture (LP) are both essential methods of diagnosing viral encephalitis. Computed tomography (CT) or magnetic resonance imaging (MRI) help identify increased intracranial pressure and the risk of uncal herniation before performing an LP. Cerebrospinal fluid (CSF), if analyzed, should be analyzed for opening pressure, cell counts, glucose, protein, and IgG and IgM antibodies. CSF testing should also include polymerase chain reaction (PCR) testing for herpes simplex viruses 1 and 2 and enteroviruses. About 10% of patients have normal CSF results. Additional testing, such as serology for various arboviruses and HIV testing, may also be performed based on the individual's history and symptoms. Brain biopsy and body fluid specimen cultures and PCR may also be useful in some cases. Electroencephalography (EEG) is abnormal in more than 80% of viral encephalitis cases, including those who are experiencing seizures, and may need to be monitored continuously to identify non-convulsive status. Lack of testing resources may prevent accurate diagnosis. Test results specific to certain viruses include: For herpes simplex virus encephalitis, a CT scan may show low-density lesions in the temporal lobe. These lesions usually appear 3 to 5 days after the start of the infection. Japanese encephalitis often has distinct EEG patterns, including diffuse delta activity with spikes, diffuse continuous delta activity, and alpha coma activity. A broad differential diagnosis can be performed that looks at many potential causes of the encephalitis, infectious and noninfectious. Potential alternatives to viral encephalitis include malignancy , autoimmune or paraneoplastic diseases such as anti-NMDA receptor encephalitis , a brain abscess , tuberculosis or drug-induced delirium , exposure to certain drugs or toxins , neurosyphilis , vascular disease, metabolic disease, or encephalitis from infection caused by a bacterium, fungus, protozoan, or parasitic worm. In children, differential diagnosis may not be able to distinguish between viral encephalitis and immune-mediated inflammatory CNS diseases, such as acute disseminated encephalomyelitis , as well as immune-mediated encephalitis, so other diagnostic methods may need to be used. If viral encephalitis is suspected, then questions can be asked about the individual's history and physical examination can be performed. Important aspects of one's history include immune status, exposure to animals, including insects, travel history, vaccination history, geography, and time of year. Symptoms usually occur acutely, and the most common symptoms of infection are fever, headache, altered mental status, sensitivity to light , stiff neck and back, vomiting, confusion, and, in severe cases, seizures , paralysis, and coma. Neuropsychiatric features such as behavioral changes, hallucinations, or cognitive decline are frequent. Severe symptoms are most common among infants and the elderly. Most infections are asymptomatic, lacking symptoms, whereas most symptomatic cases are mild illnesses. Virus-specific symptoms may also exist or tests may indicate one virus. Specific examples include: The brain histology of viral encephalitis shows dead neurons with nuclear dissolution and elevated eosinophil count, called hypereosinophilia , within cells' cytoplasm when viewed with an optical microscope . Because encephalitis is an inflammatory response, inflammatory cells situated near blood vessels, such as microglia , macrophages , and lymphocytes , are visible. Virions within neurons are visible via electron microscopes . Neuroimaging and lumbar puncture (LP) are both essential methods of diagnosing viral encephalitis. Computed tomography (CT) or magnetic resonance imaging (MRI) help identify increased intracranial pressure and the risk of uncal herniation before performing an LP. Cerebrospinal fluid (CSF), if analyzed, should be analyzed for opening pressure, cell counts, glucose, protein, and IgG and IgM antibodies. CSF testing should also include polymerase chain reaction (PCR) testing for herpes simplex viruses 1 and 2 and enteroviruses. About 10% of patients have normal CSF results. Additional testing, such as serology for various arboviruses and HIV testing, may also be performed based on the individual's history and symptoms. Brain biopsy and body fluid specimen cultures and PCR may also be useful in some cases. Electroencephalography (EEG) is abnormal in more than 80% of viral encephalitis cases, including those who are experiencing seizures, and may need to be monitored continuously to identify non-convulsive status. Lack of testing resources may prevent accurate diagnosis. Test results specific to certain viruses include: For herpes simplex virus encephalitis, a CT scan may show low-density lesions in the temporal lobe. These lesions usually appear 3 to 5 days after the start of the infection. Japanese encephalitis often has distinct EEG patterns, including diffuse delta activity with spikes, diffuse continuous delta activity, and alpha coma activity.A broad differential diagnosis can be performed that looks at many potential causes of the encephalitis, infectious and noninfectious. Potential alternatives to viral encephalitis include malignancy , autoimmune or paraneoplastic diseases such as anti-NMDA receptor encephalitis , a brain abscess , tuberculosis or drug-induced delirium , exposure to certain drugs or toxins , neurosyphilis , vascular disease, metabolic disease, or encephalitis from infection caused by a bacterium, fungus, protozoan, or parasitic worm. In children, differential diagnosis may not be able to distinguish between viral encephalitis and immune-mediated inflammatory CNS diseases, such as acute disseminated encephalomyelitis , as well as immune-mediated encephalitis, so other diagnostic methods may need to be used. Treatment of viral encephalitis is primarily supportive with intravenous antiviral therapy due to there being no specific medical therapy for most viral infections involving the central nervous system. Individuals may require intensive care for frequent neurological exams or respiratory support, and treatment for electrolyte disturbance, autonomic disregulation, and renal and hepatic dysfunction, as well as for seizures and non-compulsive status epilepticus . A very specific exception is herpes simplex virus (HSV) encephalitis, which can be treated with acyclovir for 2 to 3 weeks if it is provided early enough. Acyclovir significant decreases morbidity and mortality of HSV encephalitis and limits the long-term behavioral and cognitive impairments that occur with illness. As such, and because HSV is the most common cause of viral encephalitis, acyclovir is often administered as soon as possible to all patients suspected of having viral encephalitis even if the exact viral origin is not yet known. Viral resistance to acyclovir rarely occurs, primarily among the immunocompromised, in which case foscarnet should be used. Although not as effective, nucleoside analogs are used for other herpesviruses as well, such as acyclovir, with possible adjunctive corticosteroids for immunocompetent individuals, for varicella-zoster virus encephalitis and a combination of ganciclovir and foscarnet for cytomegalovirus encephalitis. Serial intracranial pressure (ICP) is important to monitor as elevated ICP is associated with poor prognosis. Elevated ICP can be relieved with steroids and mannitol , though there is limited data of the efficacy of such treatment with regards to viral encephalitis. Seizures can be managed with valproic acid or phenytoin . Status epilepticus may required benzodiazepines . Antipsychotic drugs may be needed for a short time period if behavior alternations are present. Given the possibility of complications developing from viral encephalitis, an interdisciplinary team consisting of the clinicians, therapists, rehabilitation specialists, and speech therapists is important in order to help patients. If treated, most individuals recover from viral encephalitis without long-term problems related to the illness. Mortality rates vary for those who do not receive treatment, for example being about 70% for herpes encephalitis but low for the La Crosse virus. Individuals who remain symptomatic after initial infection may have difficulty concentrating, behavior or speech disorders, or memory loss. Rarely, individuals may remain in a persistent vegetative state . The most common long-term complication of viral encephalitis is seizures that may occur in 10% to 20% of patients over several decades. These seizures are resistant to medical therapy. However, individuals who have unilateral mesial temporal lobe seizures after viral encephalitis have good results following neurosurgery . Prognoses related to specific viruses include: For Eastern equine encephalitis, some children may experience seizures, severe intellectual disability, and various forms of paralysis. For Japanese encephalitis, extrapyramidal symptoms relating to motor function may remain. For St. Louis encephalitis, low blood sodium level and excess, unsuppressable release of antidiuretic hormone For Western equine encephalitis, some children may experience seizures and behavioral changes. For pregnant women infected with Zika virus, the newborn child may have microcephaly. Other potential complications following viral encephalitis include: While the etiology of many cases of encephalitis is unknown, viruses account for about 70% of confirmed encephalitis cases, with the herpes simplex virus being the most common cause at about 50% of encephalitis cases. The incidence of viral encephalitis is about 3.5 to 7.5 per 100,000 people, with the highest incidence among the young and the elderly. Viral encephalitis caused by some viruses, such as the measles virus and the mumps virus, has become less common due to widespread vaccination. For others, such as Epstein-Barr virus and cytomegalovirus, incidence has increased due to the increased prevalence of AIDS , organ transplantation , and chemotherapy , which have increased the number of immunocompromised people who have weakened immune systems or who are susceptible to opportunistic infections . Time of the year, geography, and animal, including insect, exposure are also important. For example, arbovirus infections are seasonal and cause viral encephalitis at the highest rate during the summer and early fall when mosquitos are most active. Similarly, those who live in warm, humid climates where there are more mosquitos are more likely to experience viral encephalitis. As many encephalitic viruses are transmitted by mosquitos, many prevention efforts revolve around preventing mosquito bites. In areas where such arboviruses are widespread, people should use protective clothing and should sleep under a mosquito net. Removing containers of stagnant water and spraying insecticides can be beneficial. Activities that increase the likelihood of tick bites should be avoided. Vaccines against some arboviruses that cause viral encephalitis exist, such as those against Eastern equine encephalitis, Western equine encephalitis, and Venezuelan equine encephalitis. Although these vaccines are not perfectly effective, they are recommended for people who live in or travel to high-risk areas. Some vaccines that are included in standard vaccination programs, such as the MMR vaccine , which prevents measles, mumps, and rubella, are also capable of preventing viral encephalitis.

Wiki

Chikungunya

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

Genital herpes

Genital herpes is a herpes infection of the genitals caused by the herpes simplex virus (HSV). Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers . Flu-like symptoms , such as fever, aching, or swollen lymph nodes , may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder. The disease is typically spread by direct genital contact with the skin surface or secretions of someone who is infected. This may occur during sex , including anal , oral , and manual sex . Sores are not required for transmission to occur. The risk of spread between a couple is about 7.5% over a year. HSV is classified into two types, HSV-1 and HSV-2. While historically HSV-2 was more common, genital HSV-1 has become more common in the developed world . Diagnosis may occur by testing lesions using either PCR or viral culture or blood tests for specific antibodies . Efforts to prevent infection include not having sex , using condoms , and only having sex with someone who is not infected. Once infected, there is no cure. Antiviral medications may, however, prevent outbreaks or shorten outbreaks if they occur. The long-term use of antivirals may also decrease the risk of further spread. In 2015, about 846 million people (12% of the world population) had genital herpes. In the United States, more than one in six people between the ages of 14 and 49 have the disease. Women are more commonly infected than men. Rates of disease caused by HSV-2 have decreased in the United States between 1990 and 2010. Complications may rarely include aseptic meningitis , an increased risk of HIV/AIDS if exposed to HIV-positive individuals, and spread to the baby during childbirth resulting in neonatal herpes . In males, the lesions occur on the glans penis , shaft of the penis or other parts of the genital region, on the inner thigh, buttocks, or anus . In females, lesions appear on or near the pubis , clitoris or other parts of the vulva , buttocks or anus. Other common symptoms include pain, itching, and burning. Less frequent, yet still common, symptoms include discharge from the penis or vagina , fever , headache , muscle pain ( myalgia ), swollen and enlarged lymph nodes and malaise . Women often experience additional symptoms that include painful urination ( dysuria ) and cervicitis . Herpetic proctitis (inflammation of the anus and rectum) is common for individuals participating in anal intercourse . After 2–3 weeks, existing lesions progress into ulcers and then crust and heal, although lesions on mucosal surfaces may never form crusts. In rare cases, involvement of the sacral region of the spinal cord can cause acute urinary retention and one-sided symptoms and signs of myeloradiculitis (a combination of myelitis and radiculitis ): pain, sensory loss, abnormal sensations ( paresthesia ) and rash. Historically, this has been termed Elsberg syndrome, although this entity is not clearly defined. After a first episode of herpes genitalis caused by HSV-2 , there will be at least one recurrence in approximately 80% of people, while the recurrence rate for herpes genitalis caused by HSV-1 is approximately 50%. Herpes genitalis caused by HSV-2 recurs on average four to six times per year, while that of HSV-1 infection occurs only about once per year. People with recurrent genital herpes may be treated with suppressive therapy , which consists of daily antiviral treatment using acyclovir, valacyclovir or famciclovir. Suppressive therapy may be useful in those who have at least four recurrences per year but the quality of the evidence is poor. People with lower rates of recurrence will probably also have fewer recurrences with suppressive therapy. Suppressive therapy should be discontinued after a maximum of one year to reassess recurrence frequency. After a first episode of herpes genitalis caused by HSV-2 , there will be at least one recurrence in approximately 80% of people, while the recurrence rate for herpes genitalis caused by HSV-1 is approximately 50%. Herpes genitalis caused by HSV-2 recurs on average four to six times per year, while that of HSV-1 infection occurs only about once per year. People with recurrent genital herpes may be treated with suppressive therapy , which consists of daily antiviral treatment using acyclovir, valacyclovir or famciclovir. Suppressive therapy may be useful in those who have at least four recurrences per year but the quality of the evidence is poor. People with lower rates of recurrence will probably also have fewer recurrences with suppressive therapy. Suppressive therapy should be discontinued after a maximum of one year to reassess recurrence frequency. Genital herpes can be spread by viral shedding prior to and following the formation of ulcers. The risk of spread between a couple is about 7.5% over a year (for unprotected sex). The likelihood of transferring genital herpes from one person to another is decreased by external condom use by 50%, by internal condom by 50%, and refraining from sex during an active outbreak. The longer a partner has had the infection, the lower the transmission rate. An infected person may further decrease transmission risks by maintaining a daily dose of antiviral medications. Infection by genital herpes occurs in about 1 in every 1,000 sexual acts. Because herpes simplex virus (HSV) infection is common and not routinely screened for in the general population, complete prevention of the transmission of genital herpes is difficult. To reduce the chance of contracting herpes simplex virus, external condoms for the penis may be used during oral sex , vaginal sex , and anal sex . Internal condoms for the vagina may be used during oral sex or vaginal sex. Internal condoms and external condoms should not be used simultaneously. Dental dams may be used during oral sex involving the vagina or anus. Decreasing the number of sexual partners a person has may also decrease the chance of contracting HSV. People who have sexual relations with others may get tested for HSV. In people who have been diagnosed with genital herpes, transmission to others may be prevented through suppressive antiviral drugs. This option is 90% effective in preventing the transmission of HSV and is a commonly used option for sexual and/or romantic partners or those who plan on becoming pregnant. Those who are aware that they have genital herpes should notify their partner(s). Genital herpes may be diagnosed through a physical examination by a doctor or through a herpes simplex virus (HSV) test by sampling fluid within a genital blister or blood for HSV antibodies . Herpes simplex virus testing is recommended for those who have symptoms of herpes or who have a sexual partner who has a herpes infection. There is currently no recommendation for asymptomatic screening for genital herpes. False negative test results may occur if the test is performed late in the course of the illness or if the test sample is not appropriately acquired. Testing people for HSV when they are asymptomatic is not recommended due to the high false-positivity rate. A false positive test may cause relationship difficulties. Women who have genital herpes before pregnancy have a very low risk of transmitting herpes simplex virus to the baby during delivery . In the United States, 20-25% of pregnant women have genital herpes; however, fewer than 0.1% of babies born get neonatal herpes during delivery. Per the U.S. Preventive Services Task Force, routine screening for pregnant women without a history of genital herpes is not recommended. Serologic (blood) antibody testing in asymptomatic patients without history has been shown to frequently have false positive and false negative test results which may lead to anxiety, labeling, or false reassurance with minimal improvements in health outcomes of reducing neonatal herpes transmission. [ citation needed ] Pregnant women should notify their doctor if they show symptoms of genital herpes. At the time of delivery, women should be physically examined for signs of genital herpes. If a pregnant woman is symptomatic during delivery, a Cesarean section is the safest method of preventing contact and transmission of herpes simplex virus between the mother and the baby. Alternatively, some physicians use the drug acyclovir to treat pregnant women with genital herpes at 36 weeks until delivery to prevent the recurrence of symptoms and reduce the risk of transmission during delivery. Acyclovir is not approved for this purpose by the FDA; however, acyclovir's manufacturer has tracked pregnant women who have taken the drug during pregnancy, and there is no evidence that shows any risks for the infant. Acyclovir may help reduce the frequency of symptomatic recurrence near term but may not definitively protect against transmission in all cases. This may be favorable particularly for women who prefer to have a vaginal delivery instead of cesarean section. [ citation needed ]There is no cure for the disease. Skin lesions disappear without treatment within a few weeks, but treatment accelerates the healing of lesions, reduces symptoms, and helps prevent or reduce recurrent outbreaks of the disease. Antiviral medications provide clinical benefits to those who are symptomatic and is the primary means of management once infected. The main goal for the use of antiviral medications is to treat the first outbreak or to prevent genital herpes recurrences, improve quality of life, and help suppress the virus to sexual transmission to partners. Three FDA-approved antiviral medications have clinical benefits in controlling the signs and symptoms of genital herpes when used for first clinical symptoms and recurrent episodes or when used as daily suppressive therapy. These medications are acyclovir, valacyclovir, and famciclovir and have been shown to be safe with long-term use. Acyclovir is an antiviral medication and reduces the pain and the number of lesions in the initial case of genital herpes. Furthermore, it decreases the frequency and severity of recurrent infections. It comes in capsules , tablets , and ointment . However, topical ointment with acyclovir is discouraged since it offers minimal clinical benefits. Valacyclovir is a prodrug that is converted to acyclovir once in the body. It helps relieve the pain and discomfort and speeds healing of sores. It only comes in caplets and its advantage is that it has a longer duration of action than acyclovir. Famciclovir is another antiviral drug that belongs to the same class. Famciclovir is a prodrug that is converted to penciclovir in the body . The latter is the one active against the viruses. It has a longer duration of action than acyclovir and it only comes in tablets. The first time an individual experiences genital herpes, they may have prolonged clinical illness with severe genital ulceration. Furthermore, for those who have mild clinical symptoms initially may experience severe recurrent infections later. Typical recommended regimens for first clinical episodes of genital herpes may be something like: A treatment longer than 10 days may be recommended if the genital ulcers have not fully healed. Most individuals who experience a symptomatic first episode of genital herpes will experience recurrence of genital lesions at some point in the future. Asymptomatic shedding can also occur where an individual may not have genital ulcerations present but still possibly transmit the virus to other partners. It is important for patients to have a discussion with their primary care doctor for options of receiving either episodic treatment or long-term suppressive therapies. Suppressive therapy has been shown effective in reducing recurrent genital herpes in as high as 80% which can tremendously help in improving quality of life since patients claim having minimal symptomatic episodes. Long-term use of anti-virals like acyclovir, valacyclovir, and famciclovir have been shown to be safe and effective. Furthermore, long-term treatment of genital herpes with valacyclovir daily has shown to decrease the rates of transmission. It is important for patients to continue suppressive therapy in conjunction to consistent condom use and sexual abstinence during recurrent episodes to decrease transmission as well. To decrease symptoms during an outbreak of genital herpes, people can use an ice pack on the affected areas, take a warm bath, keep the genitals dry when not bathing, and take over-the-counter pain relief medication such as ibuprofen or acetaminophen . The first time an individual experiences genital herpes, they may have prolonged clinical illness with severe genital ulceration. Furthermore, for those who have mild clinical symptoms initially may experience severe recurrent infections later. Typical recommended regimens for first clinical episodes of genital herpes may be something like: A treatment longer than 10 days may be recommended if the genital ulcers have not fully healed.Most individuals who experience a symptomatic first episode of genital herpes will experience recurrence of genital lesions at some point in the future. Asymptomatic shedding can also occur where an individual may not have genital ulcerations present but still possibly transmit the virus to other partners. It is important for patients to have a discussion with their primary care doctor for options of receiving either episodic treatment or long-term suppressive therapies. Suppressive therapy has been shown effective in reducing recurrent genital herpes in as high as 80% which can tremendously help in improving quality of life since patients claim having minimal symptomatic episodes. Long-term use of anti-virals like acyclovir, valacyclovir, and famciclovir have been shown to be safe and effective. Furthermore, long-term treatment of genital herpes with valacyclovir daily has shown to decrease the rates of transmission. It is important for patients to continue suppressive therapy in conjunction to consistent condom use and sexual abstinence during recurrent episodes to decrease transmission as well. To decrease symptoms during an outbreak of genital herpes, people can use an ice pack on the affected areas, take a warm bath, keep the genitals dry when not bathing, and take over-the-counter pain relief medication such as ibuprofen or acetaminophen . About 16 percent of Americans between the ages of 14 and 49 are infected with genital herpes, making it one of the most common sexually transmitted infections. More than 85% of those with HSV-2 are unaware of their infection. Approximately 776,000 people in the United States get new herpes infections every year. Tests for herpes are not routinely included among STI screenings. Performers in the pornography industry are screened for HIV, chlamydia , and gonorrhea with an optional panel of tests for hepatitis B, hepatitis C and syphilis, but not herpes. Testing for herpes is controversial since the results are not always accurate or helpful. Most sex workers and performers will contract herpes at some point in their careers whether they use protection or not. Early 20th century public health legislation in the United Kingdom required compulsory treatment for sexually transmitted infections but did not include herpes because it was not serious enough. As late as 1975, nursing textbooks did not include herpes as it was considered no worse than a common cold. After the development of acyclovir in the 1970s, the drug company Burroughs Wellcome launched an extensive marketing campaign that publicized the illness, including creating victim's support groups. There are efforts to develop a vaccine for active outbreaks of the virus—despite most cases being asymptomatic—but the results thus far have not been able to do so or eliminate transmission.

Wiki

Chikungunya

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

Plantar wart

A plantar wart , or verruca vulgaris , is a wart occurring on the bottom of the foot or toes . Its color is typically similar to that of the skin . Small black dots often occur on the surface. One or more may occur in an area. They may result in pain with pressure such that walking is difficult. They are caused by the human papillomavirus (HPV). A break in the skin is required for infection to occur. Risk factors include use of communal showers, having had prior warts, and poor immune function . Diagnosis is typically based on symptoms. Treatment is only needed if it is causing symptoms. This may include salicylic acid , cryotherapy , chemo -based fluorouracil or bleomycin , and surgical removal. The skin atop the lesion should generally be removed before treatment. In about a third to two-thirds of cases, they go away without specific treatment, but this may take a few years. Plantar warts are common. Children and young adults are most often affected. Their colors are typically similar to that of the nearby skin . Small, black dots may occur on their surfaces. One or more may occur in an area. They may result in pain with pressure such that walking may be difficult. Plantar warts are benign epithelial tumors generally caused by infection by human papillomavirus types 1, 2, 4, 60, or 63, but have also been caused by types 57, 65, 66, and 156. These types are classified as clinical (visible symptoms). The virus attacks compromised skin through direct contact, possibly entering through tiny cuts and abrasions in the stratum corneum (outermost layer of skin). After infection, warts may not become visible for several weeks or months. Because of pressure on the sole of the foot or finger , the wart is pushed inward and a layer of hard skin may form over the wart. A plantar wart can be painful if left untreated. Warts may spread through autoinoculation , by infecting nearby skin, or by contaminated walking surfaces. They may fuse or develop into clusters called mosaic warts. A plantar wart is a small lesion that appears on the surface of the skin and typically resembles a cauliflower , with tiny black petechiae (tiny hemorrhages under the skin) in the center. Pinpoint bleeding may occur when these are scratched. Plantar warts occur on the soles of feet and toes. They may be painful when standing or walking. [ citation needed ] Plantar warts are often similar to calluses or corns , but can be differentiated by close observation of skin striations. Feet are covered in friction ridges, which are akin to fingerprints of the feet. Friction ridges are disrupted by plantar warts; if the lesion is not a plantar wart, the striations continue across the top layer of the skin. Plantar warts tend to be painful on application of pressure from either side of the lesion rather than direct pressure, unlike calluses (which tend to be painful on direct pressure, instead). [ citation needed ]HPV is spread by direct and indirect contact from an infected host. Avoiding direct contact with contaminated surfaces such as communal changing rooms and shower floors and benches, avoiding sharing of shoes and socks and avoiding contact with warts on other parts of the body and on the bodies of others may help reduce the spread of infection. Infection is less common among adults than children. As all warts are contagious, precautions should be taken to avoid spreading them. Recommendations include: Plantar warts are not prevented by inoculation with HPV vaccines because the warts are caused by different strains of HPV. Gardasil protects against strains 6, 11, 16, and 18, and Cervarix protects against 16 and 18, whereas plantar warts are caused by strains 1, 2, 4, and 63. [ dubious – discuss ]A number of treatments have been found to be effective. A 2012 review of different treatments for skin warts in otherwise healthy people concluded modest benefit from salicylic acid, and cryotherapy appears similar to salicylic acid. Salicylic acid, the treatment of warts by keratolysis , involves the peeling away of dead surface skin cells with keratolytic chemicals such as salicylic acid or trichloroacetic acid . These are available in over-the-counter products, but in higher concentrations may need to be prescribed by a physician. A 12-week daily treatment with salicylic acid has been shown to lead to a complete clearance of warts in 10–15% of the cases. Formic acid , topical, is a common treatment for plantar warts, which works by being applied over a period of time, causing the body to reject the wart. Fluorouracil cream, a chemotherapy agent sometimes used to treat skin cancer , can be used on particularly resistant warts, by blocking viral DNA and RNA production and repair. Bleomycin , a more potent chemotherapy drug, can be injected into deep warts, destroying the viral DNA or RNA. Bleomycin is notably not US FDA approved for this purpose. Possible side effects include necrosis of the digits, nail loss, and Raynaud syndrome . The usual treatment is one or two injections. Immunotherapy , as intralesional injection of antigens ( mumps , candida or trichophytin antigens USP), is a wart treatment that may trigger a host immune response to the wart virus, resulting in wart resolution. It is now recommended as a second-line therapy. Liquid nitrogen and similar cryosurgery methods are common surgical treatments, which act by freezing the external cell structure of the warts, destroying the live tissue. [ citation needed ] Electrodesiccation and surgical excision may produce scarring. [ citation needed ] Laser surgery is generally a last resort treatment, as it is expensive and painful, but may be necessary for large, hard-to-cure warts. Cauterization may be effective as a prolonged treatment. As a short-term treatment, cauterization of the base with anesthetic can be effective, but this method risks scarring or keloids . Subsequent surgical removal, if necessary, also risks keloids and/or recurrence in the operative scar. Salicylic acid, the treatment of warts by keratolysis , involves the peeling away of dead surface skin cells with keratolytic chemicals such as salicylic acid or trichloroacetic acid . These are available in over-the-counter products, but in higher concentrations may need to be prescribed by a physician. A 12-week daily treatment with salicylic acid has been shown to lead to a complete clearance of warts in 10–15% of the cases. Formic acid , topical, is a common treatment for plantar warts, which works by being applied over a period of time, causing the body to reject the wart. Fluorouracil cream, a chemotherapy agent sometimes used to treat skin cancer , can be used on particularly resistant warts, by blocking viral DNA and RNA production and repair. Bleomycin , a more potent chemotherapy drug, can be injected into deep warts, destroying the viral DNA or RNA. Bleomycin is notably not US FDA approved for this purpose. Possible side effects include necrosis of the digits, nail loss, and Raynaud syndrome . The usual treatment is one or two injections. Immunotherapy , as intralesional injection of antigens ( mumps , candida or trichophytin antigens USP), is a wart treatment that may trigger a host immune response to the wart virus, resulting in wart resolution. It is now recommended as a second-line therapy. Liquid nitrogen and similar cryosurgery methods are common surgical treatments, which act by freezing the external cell structure of the warts, destroying the live tissue. [ citation needed ] Electrodesiccation and surgical excision may produce scarring. [ citation needed ] Laser surgery is generally a last resort treatment, as it is expensive and painful, but may be necessary for large, hard-to-cure warts. Cauterization may be effective as a prolonged treatment. As a short-term treatment, cauterization of the base with anesthetic can be effective, but this method risks scarring or keloids . Subsequent surgical removal, if necessary, also risks keloids and/or recurrence in the operative scar.

Wiki

Chikungunya

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

Chikungunya

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

Postherpetic neuralgia

Postherpetic neuralgia ( PHN ) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus ( herpes zoster , also known as shingles ). PHN is defined as pain in a dermatomal distribution that lasts for at least 90 days after an outbreak of herpes zoster. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain or to painful stimuli . Abnormal sensations and itching may also occur. Postherpetic neuralgia is the most common long-term complication of herpes zoster, and occurs in approximately 20% of patients with shingles. Risk factors for PHN include older age, severe prodrome or rash , severe acute zoster pain, ophthalmic involvement, immunosuppression , and chronic conditions such as diabetes mellitus and lupus . The pain from postherpetic neuralgia can be very severe and debilitating. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms. Affected individuals often experience a decrease in their quality of life . Shingles vaccination is the only way for adults to be protected against both shingles and postherpetic neuralgia, with the vaccine Shingrix providing 90% protection from postherpetic neuralgia. The chickenpox vaccine is approved for infants to prevent chickenpox , which also protects against PHN from a herpes zoster infection. Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus ( herpes zoster , also known as shingles). Typically, the nerve pain (neuralgia) is confined to an area of skin innervated by a single sensory nerve , which is known as a dermatome . PHN is defined as dermatomal nerve pain that persists for more than 90 days after an outbreak of herpes zoster affecting the same dermatome. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain (mechanical allodynia ) or to painful stimuli ( hyperalgesia ). Abnormal sensations and itching may also occur. The nerve pain of PHN is thought to result from damage in a peripheral nerve that was affected by the reactivation of the varicella zoster virus or troubles after chemotherapy. PHN typically begins when the herpes zoster vesicles have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition called zoster sine herpete . There is no treatment that modifies the disease course of PHN; therefore, controlling the affected person's symptoms is the main goal of treatment. Medications applied to the skin such as capsaicin or topical anesthetics (e.g., lidocaine ) are used for mild pain and can be used in combination with oral medications for moderate to severe pain. Oral anticonvulsant medications such as gabapentin and pregabalin are also approved for treatment of PHN. Tricyclic antidepressants reduce PHN pain, but their use is limited by side effects. Opioid medications are not generally recommended for treatment except in specific circumstances. Such cases should involve a pain specialist in patient care due to mixed evidence of efficacy and concerns about potential for abuse and addiction . Shingles vaccination is the only way for adults to be protected against both shingles and postherpetic neuralgia, with the vaccine Shingrix providing 90% protection from postherpetic neuralgia. The chickenpox vaccine is approved for infants to prevent chickenpox , which also protects against PHN from a herpes zoster infection. PHN is the most common long-term complication of herpes zoster. The incidence and prevalence of PHN are uncertain due to varying definitions. Approximately 20% of people affected by herpes zoster report pain in the affected area three months after the initial episode of herpes zoster, and 15% of people similarly report this pain two years after the herpes zoster rash. Since herpes zoster occurs due to reactivation of the varicella zoster virus, which is more likely to occur with a weakened immune system , both herpes zoster and PHN occur more often in the elderly. Risk factors for PHN include older age, severe prodrome or rash , severe acute zoster pain, ophthalmic involvement, immunosuppression , and chronic conditions such as diabetes mellitus and lupus . PHN is often very painful and can be quite debilitating. Affected individuals often experience a decrease in their quality of life . Symptoms: [ citation needed ] With resolution of the herpes zoster eruption, pain that continues for three months or more is defined as postherpetic neuralgia. Pain is variable, from discomfort to very severe, and may be described as burning, stabbing, or gnawing. Signs: [ citation needed ] Area of previous herpes zoster may show evidence of cutaneous scarring. Sensation may be altered over the areas involved, in the form of either hypersensitivity or decreased sensation. In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the nerves involved also control muscle movement.Postherpetic neuralgia is thought to be due to nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain , and may persist or recur for months, years, or for life. A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia neurons . Injury to sensory nerves induces neurochemical, physiological, and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory interneuron loss. Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and TRPV1 channels. These changes contribute to increased NMDA glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia. [ citation needed ]Lab Studies: [ citation needed ] Imaging studies: [ citation needed ] Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients. At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia. Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain.Shingles vaccination is the only way for adults to be protected against both shingles and postherpetic neuralgia, with two vaccines approved for use in people over age 50. The zoster vaccine Shingrix provides around 90% protection from postherpetic neuralgia, and has been used in many countries since 2017. The earlier vaccine Zostavax provides lesser protection against shingles, and PHN. The varicella vaccine is approved for infants to prevent chickenpox , which also protects against PHN from a herpes zoster infection. Vaccination decreases the overall incidence of virus reactivation, and also decreases the severity of disease development and incidence of PHN if reactivation does occur. A 2013 Cochrane meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and aciclovir . Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to oral famciclovir treatment within 72 hours of HZ rash onset. Studies using valaciclovir treatment were not included in the meta-analysis. PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. Patients who are prescribed oral antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking oral antiviral agents. Shingles vaccination is the only way for adults to be protected against both shingles and postherpetic neuralgia, with two vaccines approved for use in people over age 50. The zoster vaccine Shingrix provides around 90% protection from postherpetic neuralgia, and has been used in many countries since 2017. The earlier vaccine Zostavax provides lesser protection against shingles, and PHN. The varicella vaccine is approved for infants to prevent chickenpox , which also protects against PHN from a herpes zoster infection. Vaccination decreases the overall incidence of virus reactivation, and also decreases the severity of disease development and incidence of PHN if reactivation does occur. A 2013 Cochrane meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and aciclovir . Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to oral famciclovir treatment within 72 hours of HZ rash onset. Studies using valaciclovir treatment were not included in the meta-analysis. PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. Patients who are prescribed oral antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking oral antiviral agents. The pain from postherpetic neuralgia can be very severe and requires immediate treatment. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms. Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe. Topical medications for PHN include low-dose (0.075%) and high-dose (8%) capsaicin and anesthetics such as lidocaine patches. Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited. A meta-analysis of multiple small placebo -controlled randomized controlled trials found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ( number needed to treat (NNT) =2). Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ( redness and a burning or stinging sensation with application) and the need to apply it four times daily. Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3). A single topical application of a high-dose capsaicin patch over the affected area after numbing the area with a topical anesthetic has also been found to relieve PHN-associated pain. For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11). Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered. Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. Tricyclic antidepressants (TCAs), such as nortriptyline or desipramine , are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3). Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as dry mouth , constipation , or urinary retention ( number needed to harm =16). The anticonvulsant medications pregabalin and gabapentin also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4–5 people treated (NNT=4–5). Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5). Opioids such as tramadol , methadone , oxycodone , and morphine have not been well-studied for postherpetic neuralgia treatment. Acetaminophen and nonsteroidal anti-inflammatory drugs are thought to be ineffective and have not undergone rigorous study for PHN. Pharmacological treatment of PHN is unsatisfactory for many patients and there is a clinical need for new treatments. Between 2016 and 2023, 18 clinical trials have been carried out evaluating 15 molecules with pharmacological actions on nine different molecular targets: antagonism of the angiotensin type 2 receptor (AT2R) (olodanrigan), inhibition of the α2δ subunit of the voltage-gated calcium channel (VGCC)(crisugabalin, mirogabalin and pregabalin), activated sodium channel (VGSC) blockade (funapide and lidocaine), cyclooxygenase-1 (COX-1) inhibition (TRK-700), adapter-associated kinase 1 inhibition ( AAK1) (LX9211), lanthionine synthase C-like protein (LANCL) activation (LAT8881), N-methyl-D-aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone e hydromorphone) and nerve growth factor (NGF) inhibition (fulranumab). Of them, some of them report promising results while others did not work. Hopefully, these experimental treatments will result in better clinical management of PHN.Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe. Topical medications for PHN include low-dose (0.075%) and high-dose (8%) capsaicin and anesthetics such as lidocaine patches. Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited. A meta-analysis of multiple small placebo -controlled randomized controlled trials found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ( number needed to treat (NNT) =2). Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ( redness and a burning or stinging sensation with application) and the need to apply it four times daily. Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3). A single topical application of a high-dose capsaicin patch over the affected area after numbing the area with a topical anesthetic has also been found to relieve PHN-associated pain. For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11). Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered. Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. Tricyclic antidepressants (TCAs), such as nortriptyline or desipramine , are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3). Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as dry mouth , constipation , or urinary retention ( number needed to harm =16). The anticonvulsant medications pregabalin and gabapentin also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4–5 people treated (NNT=4–5). Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5). Opioids such as tramadol , methadone , oxycodone , and morphine have not been well-studied for postherpetic neuralgia treatment. Acetaminophen and nonsteroidal anti-inflammatory drugs are thought to be ineffective and have not undergone rigorous study for PHN. Pharmacological treatment of PHN is unsatisfactory for many patients and there is a clinical need for new treatments. Between 2016 and 2023, 18 clinical trials have been carried out evaluating 15 molecules with pharmacological actions on nine different molecular targets: antagonism of the angiotensin type 2 receptor (AT2R) (olodanrigan), inhibition of the α2δ subunit of the voltage-gated calcium channel (VGCC)(crisugabalin, mirogabalin and pregabalin), activated sodium channel (VGSC) blockade (funapide and lidocaine), cyclooxygenase-1 (COX-1) inhibition (TRK-700), adapter-associated kinase 1 inhibition ( AAK1) (LX9211), lanthionine synthase C-like protein (LANCL) activation (LAT8881), N-methyl-D-aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone e hydromorphone) and nerve growth factor (NGF) inhibition (fulranumab). Of them, some of them report promising results while others did not work. Hopefully, these experimental treatments will result in better clinical management of PHN.Medications applied to the skin can be used alone if the pain from PHN is mild or in combination with oral medications if the pain is moderate to severe. Topical medications for PHN include low-dose (0.075%) and high-dose (8%) capsaicin and anesthetics such as lidocaine patches. Lidocaine patches (5% concentration) are approved in the United States and Europe to treat PHN though evidence supporting their use is limited. A meta-analysis of multiple small placebo -controlled randomized controlled trials found that for every two people treated with topical lidocaine, one person experienced at least a 50% reduction in their PHN-associated pain ( number needed to treat (NNT) =2). Low-dose capsaicin may be useful for reducing PHN-associated pain but is limited by side effects ( redness and a burning or stinging sensation with application) and the need to apply it four times daily. Approximately three people must be treated with low-dose capsaicin cream for one person to experience significant pain relief (number needed to treat =3.3). A single topical application of a high-dose capsaicin patch over the affected area after numbing the area with a topical anesthetic has also been found to relieve PHN-associated pain. For every eleven people treated with a high-dose capsaicin patch for up to 12 weeks, one person experienced a significant improvement in their pain. (number needed to treat=11). Due to the need for topical anesthesia before application of the high-dose capsaicin patch, referral to a pain specialist is generally recommended if this approach is being considered. Multiple oral medications have demonstrated efficacy in relieving postherpetic neuralgia pain. Tricyclic antidepressants (TCAs), such as nortriptyline or desipramine , are effective in reducing postherpetic neuralgia pain but are limited by their numerous side effects. For every three people treated with a tricyclic antidepressant, one person is expected to have a clinically significant reduction in their pain (NNT=3). Additionally, of every sixteen people treated with a TCA, one person is expected to stop the medication due to a bothersome side effect, such as dry mouth , constipation , or urinary retention ( number needed to harm =16). The anticonvulsant medications pregabalin and gabapentin also effectively relieve postherpetic neuralgia pain. Treatment with pregabalin leads to a reduction in pain intensity of 50% or more in one person out of every 4–5 people treated (NNT=4–5). Similarly, treatment with gabapentin also leads to a 50% reduction in pain intensity in one person out of every 7-8 people treated (NNT=7.5). Opioids such as tramadol , methadone , oxycodone , and morphine have not been well-studied for postherpetic neuralgia treatment. Acetaminophen and nonsteroidal anti-inflammatory drugs are thought to be ineffective and have not undergone rigorous study for PHN. Pharmacological treatment of PHN is unsatisfactory for many patients and there is a clinical need for new treatments. Between 2016 and 2023, 18 clinical trials have been carried out evaluating 15 molecules with pharmacological actions on nine different molecular targets: antagonism of the angiotensin type 2 receptor (AT2R) (olodanrigan), inhibition of the α2δ subunit of the voltage-gated calcium channel (VGCC)(crisugabalin, mirogabalin and pregabalin), activated sodium channel (VGSC) blockade (funapide and lidocaine), cyclooxygenase-1 (COX-1) inhibition (TRK-700), adapter-associated kinase 1 inhibition ( AAK1) (LX9211), lanthionine synthase C-like protein (LANCL) activation (LAT8881), N-methyl-D-aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone e hydromorphone) and nerve growth factor (NGF) inhibition (fulranumab). Of them, some of them report promising results while others did not work. Hopefully, these experimental treatments will result in better clinical management of PHN.The natural history of postherpetic neuralgia involves slow resolution of the pain syndrome. A subgroup of affected individuals may develop severe, long-lasting pain that does not respond to medical therapy. [ citation needed ]In the United States each year approximately 1,000,000 individuals develop herpes zoster, with nearly 1 in 3 people in the United States developing it in their lifetime. Of those individuals, approximately 10–18% develop postherpetic neuralgia. The incidence of herpes zoster, and also developing postherpetic neuralgia, both increase with age. The frequency and severity of postherpetic neuralgia increase with advancing age, occurring in 20% of people age 60–65 years old who have had herpes zoster, and in more than 30% of people over 80 years old.

Wiki

Chikungunya

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

Zika virus

Zika virus ( ZIKV ; pronounced / ˈ z iː k ə / or / ˈ z ɪ k ə / ) is a member of the virus family Flaviviridae . It is spread by daytime-active Aedes mosquitoes, such as A. aegypti and A. albopictus . Its name comes from the Ziika Forest of Uganda , where the virus was first isolated in 1947. Zika virus shares a genus with the dengue , yellow fever , Japanese encephalitis , and West Nile viruses. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. From 2007 to 2016 [ update ] , the virus spread eastward, across the Pacific Ocean to the Americas, leading to the 2015–2016 Zika virus epidemic . The infection, known as Zika fever or Zika virus disease, often causes no or only mild symptoms, similar to a very mild form of dengue fever . While there is no specific treatment, paracetamol (acetaminophen) and rest may help with the symptoms. As of April 2019, no vaccines have been approved for clinical use, however a number of vaccines are currently in clinical trials. Zika can spread from a pregnant woman to her baby. This can result in microcephaly , severe brain malformations , and other birth defects. Zika infections in adults may result rarely in Guillain–Barré syndrome . In January 2016, the United States Centers for Disease Control and Prevention (CDC) issued travel guidance on affected countries, including the use of enhanced precautions, and guidelines for pregnant women including considering postponing travel. Other governments or health agencies also issued similar travel warnings, while Colombia , the Dominican Republic , Puerto Rico , Ecuador , El Salvador , and Jamaica advised women to postpone getting pregnant until more is known about the risks. Zika virus belongs to the family Flaviviridae and the genus Flavivirus , thus is related to the dengue , yellow fever , Japanese encephalitis , and West Nile viruses. Like other flaviviruses, Zika virus is enveloped and icosahedral and has a nonsegmented, single-stranded, 10 kilobase , positive-sense RNA genome . It is most closely related to the Spondweni virus and is one of the two known viruses in the Spondweni virus clade . A positive-sense RNA genome can be directly translated into viral proteins. As in other flaviviruses, such as the similarly sized West Nile virus, the RNA genome encodes seven nonstructural proteins and three structural proteins in the form of a single polyprotein ( Q32ZE1 ). One of the structural proteins encapsulates the virus. This protein is the flavivirus envelope glycoprotein, that binds to the endosomal membrane of the host cell to initiate endocytosis. The RNA genome forms a nucleocapsid along with copies of the 12-kDa capsid protein. The nucleocapsid, in turn, is enveloped within a host-derived membrane modified with two viral glycoproteins . Viral genome replication depends on the making of double-stranded RNA from the single-stranded, positive-sense RNA (ssRNA(+)) genome followed by transcription and replication to provide viral mRNAs and new ssRNA(+) genomes. A longitudinal study shows that 6 hours after cells are infected with Zika virus , the vacuoles and mitochondria in the cells begin to swell. This swelling becomes so severe, it results in cell death, also known as paraptosis. This form of programmed cell death requires gene expression. IFITM3 is a trans-membrane protein in a cell that is able to protect it from viral infection by blocking virus attachment. Cells are most susceptible to Zika infection when levels of IFITM3 are low. Once the cell has been infected, the virus restructures the endoplasmic reticulum, forming the large vacuoles, resulting in cell death. There are two Zika lineages: the African lineage and the Asian lineage. Phylogenetic studies indicate that the virus spreading in the Americas is 89% identical to African genotypes, but is most closely related to the Asian strain that circulated in French Polynesia during the 2013 – 2014 outbreak . The Asian strain appears to have first evolved around 1928. The vertebrate hosts of the virus were primarily monkeys in a so-called enzootic mosquito-monkey-mosquito cycle, with only occasional transmission to humans. Before 2007, Zika "rarely caused recognized 'spillover' infections in humans, even in highly enzootic areas". Infrequently, however, other arboviruses have become established as a human disease and spread in a mosquito–human–mosquito cycle, like the yellow fever virus and the dengue fever virus (both flaviviruses), and the chikungunya virus (a togavirus ). Though the reason for the pandemic is unknown, dengue, a related arbovirus that infects the same species of mosquito vectors , is known in particular to be intensified by urbanization and globalization . Zika is primarily spread by Aedes aegypti mosquitoes, and can also be transmitted through sexual contact or blood transfusions . The basic reproduction number ( R 0 , a measure of transmissibility) of Zika virus has been estimated to be between 1.4 and 6.6 . In 2015, news reports drew attention to the rapid spread of Zika in Latin America and the Caribbean. At that time, the Pan American Health Organization published a list of countries and territories that experienced "local Zika virus transmission" comprising Barbados, Bolivia, Brazil, Colombia, the Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, and Venezuela. By August 2016, more than 50 countries had experienced active (local) transmission of Zika virus . Zika is primarily spread by the female Aedes aegypti mosquito, which is active mostly in the daytime. The mosquitos must feed on blood to lay eggs. : 2 The virus has also been isolated from a number of arboreal mosquito species in the genus Aedes , such as A. africanus , A. apicoargenteus , A. furcifer , A. hensilli , A. luteocephalus , and A. vittatus , with an extrinsic incubation period in mosquitoes around 10 days. The true extent of the vectors is still unknown. Zika has been detected in many more species of Aedes , along with Anopheles coustani, Mansonia uniformis , and Culex perfuscus , although this alone does not incriminate them as vectors. To detect the presence of the virus usually requires genetic material to be analysed in a lab using the technique RT-PCR . A much cheaper and faster method involves shining a light at the head and thorax of the mosquito, and detecting chemical compounds characteristic of the virus using near-infrared spectroscopy . Transmission by A. albopictus , the tiger mosquito, was reported from a 2007 urban outbreak in Gabon, where it had newly invaded the country and become the primary vector for the concomitant chikungunya and dengue virus outbreaks. New outbreaks can occur if a person carrying the virus travels to another region where A. albopictus is common. The potential societal risk of Zika can be delimited by the distribution of the mosquito species that transmit it. The global distribution of the most cited carrier of Zika, A. aegypti , is expanding due to global trade and travel. A. aegypti distribution is now the most extensive ever recorded – on parts of all continents except Antarctica, including North America and even the European periphery ( Madeira , the Netherlands, and the northeastern Black Sea coast). A mosquito population capable of carrying Zika has been found in a Capitol Hill neighborhood of Washington, DC, and genetic evidence suggests they survived at least four consecutive winters in the region. The study authors conclude that mosquitos are adapting for persistence in a northern climate. Zika virus appears to be contagious via mosquitoes for around a week after infection. The virus is thought to be infectious for a longer period of time after infection (at least 2 weeks) when transmitted via semen . Research into its ecological niche suggests that Zika may be influenced to a greater degree by changes in precipitation and temperature than dengue, making it more likely to be confined to tropical areas. However, rising global temperatures would allow for the disease vector to expand its range further north, allowing Zika to follow. Zika can be transmitted from men and women to their sexual partners; most known cases involve transmission from symptomatic men to women. As of April 2016, sexual transmission of Zika has been documented in six countries – Argentina, Australia, France, Italy, New Zealand, and the United States – during the 2015 outbreak. ZIKV can persist in semen for several months, with viral RNA detected up to one year. The virus replicates in the human testis, where it infects several cell types including testicular macrophages, peritubular cells and germ cells, the spermatozoa precursors. Semen parameters can be altered in patients for several weeks post-symptoms onset, and spermatozoa can be infectious. Since October 2016, the CDC has advised men who have traveled to an area with Zika should use condoms or not have sex for at least six months after their return as the virus is still transmissible even if symptoms never develop. Zika virus can spread by vertical (or "mother-to-child") transmission , during pregnancy or at delivery. An infection during pregnancy has been linked to changes in neuronal development of the unborn child. Severe progressions of infection have been linked to the development of microcephaly in the unborn child, while mild infections potentially can lead to neurocognitive disorders later in life. Congenital brain abnormalities other than microcephaly have also been reported after a Zika outbreak. Studies in mice have suggested that maternal immunity to dengue virus may enhance fetal infection with Zika, worsen the microcephaly phenotype and/or enhance damage during pregnancy, but it is unknown whether this occurs in humans. As of April 2016 [ update ] , two cases of Zika transmission through blood transfusions have been reported globally, both from Brazil, after which the US Food and Drug Administration (FDA) recommended screening blood donors and deferring high-risk donors for 4 weeks. A potential risk had been suspected based on a blood-donor screening study during the French Polynesian Zika outbreak, in which 2.8% (42) of donors from November 2013 and February 2014 tested positive for Zika RNA and were all asymptomatic at the time of blood donation. Eleven of the positive donors reported symptoms of Zika fever after their donation, but only three of 34 samples grew in culture. Zika is primarily spread by the female Aedes aegypti mosquito, which is active mostly in the daytime. The mosquitos must feed on blood to lay eggs. : 2 The virus has also been isolated from a number of arboreal mosquito species in the genus Aedes , such as A. africanus , A. apicoargenteus , A. furcifer , A. hensilli , A. luteocephalus , and A. vittatus , with an extrinsic incubation period in mosquitoes around 10 days. The true extent of the vectors is still unknown. Zika has been detected in many more species of Aedes , along with Anopheles coustani, Mansonia uniformis , and Culex perfuscus , although this alone does not incriminate them as vectors. To detect the presence of the virus usually requires genetic material to be analysed in a lab using the technique RT-PCR . A much cheaper and faster method involves shining a light at the head and thorax of the mosquito, and detecting chemical compounds characteristic of the virus using near-infrared spectroscopy . Transmission by A. albopictus , the tiger mosquito, was reported from a 2007 urban outbreak in Gabon, where it had newly invaded the country and become the primary vector for the concomitant chikungunya and dengue virus outbreaks. New outbreaks can occur if a person carrying the virus travels to another region where A. albopictus is common. The potential societal risk of Zika can be delimited by the distribution of the mosquito species that transmit it. The global distribution of the most cited carrier of Zika, A. aegypti , is expanding due to global trade and travel. A. aegypti distribution is now the most extensive ever recorded – on parts of all continents except Antarctica, including North America and even the European periphery ( Madeira , the Netherlands, and the northeastern Black Sea coast). A mosquito population capable of carrying Zika has been found in a Capitol Hill neighborhood of Washington, DC, and genetic evidence suggests they survived at least four consecutive winters in the region. The study authors conclude that mosquitos are adapting for persistence in a northern climate. Zika virus appears to be contagious via mosquitoes for around a week after infection. The virus is thought to be infectious for a longer period of time after infection (at least 2 weeks) when transmitted via semen . Research into its ecological niche suggests that Zika may be influenced to a greater degree by changes in precipitation and temperature than dengue, making it more likely to be confined to tropical areas. However, rising global temperatures would allow for the disease vector to expand its range further north, allowing Zika to follow. Zika can be transmitted from men and women to their sexual partners; most known cases involve transmission from symptomatic men to women. As of April 2016, sexual transmission of Zika has been documented in six countries – Argentina, Australia, France, Italy, New Zealand, and the United States – during the 2015 outbreak. ZIKV can persist in semen for several months, with viral RNA detected up to one year. The virus replicates in the human testis, where it infects several cell types including testicular macrophages, peritubular cells and germ cells, the spermatozoa precursors. Semen parameters can be altered in patients for several weeks post-symptoms onset, and spermatozoa can be infectious. Since October 2016, the CDC has advised men who have traveled to an area with Zika should use condoms or not have sex for at least six months after their return as the virus is still transmissible even if symptoms never develop. Zika virus can spread by vertical (or "mother-to-child") transmission , during pregnancy or at delivery. An infection during pregnancy has been linked to changes in neuronal development of the unborn child. Severe progressions of infection have been linked to the development of microcephaly in the unborn child, while mild infections potentially can lead to neurocognitive disorders later in life. Congenital brain abnormalities other than microcephaly have also been reported after a Zika outbreak. Studies in mice have suggested that maternal immunity to dengue virus may enhance fetal infection with Zika, worsen the microcephaly phenotype and/or enhance damage during pregnancy, but it is unknown whether this occurs in humans. As of April 2016 [ update ] , two cases of Zika transmission through blood transfusions have been reported globally, both from Brazil, after which the US Food and Drug Administration (FDA) recommended screening blood donors and deferring high-risk donors for 4 weeks. A potential risk had been suspected based on a blood-donor screening study during the French Polynesian Zika outbreak, in which 2.8% (42) of donors from November 2013 and February 2014 tested positive for Zika RNA and were all asymptomatic at the time of blood donation. Eleven of the positive donors reported symptoms of Zika fever after their donation, but only three of 34 samples grew in culture. Zika virus replicates in the mosquito's midgut epithelial cells and then its salivary gland cells. After 5–10 days, the virus can be found in the mosquito's saliva. If the mosquito's saliva is inoculated into human skin, the virus can infect epidermal keratinocytes, skin fibroblasts in the skin and the Langerhans cells . The pathogenesis of the virus is hypothesized to continue with a spread to lymph nodes and the bloodstream. Flaviviruses replicate in the cytoplasm , but Zika antigens have been found in infected cell nuclei. The viral protein numbered NS4A can lead to small head size ( microcephaly ) because it disrupts brain growth by hijacking a pathway which regulates growth of new neurons. In fruit flies, both NS4A and the neighboring NS4B restrict eye growth. Zika fever (also known as Zika virus disease) is an illness caused by Zika virus . Around 80% of cases are estimated to be asymptomatic, though the accuracy of this figure is hindered by the wide variance in data quality, and figures from different outbreaks can vary significantly. Symptomatic cases are usually mild and can resemble dengue fever . Symptoms may include fever , red eyes , joint pain , headache, and a maculopapular rash . Symptoms generally last less than seven days. It has not caused any reported deaths during the initial infection. Infection during pregnancy causes microcephaly and other brain malformations in some babies. Infection in adults has been linked to Guillain–Barré syndrome (GBS) and Zika virus has been shown to infect human Schwann cells . Diagnosis is by testing the blood, urine, or saliva for the presence of Zika virus RNA when the person is sick. In 2019, an improved diagnostic test, based on research from Washington University in St. Louis , that detects Zika infection in serum was granted market authorization by the FDA . Prevention involves decreasing mosquito bites in areas where the disease occurs, and proper use of condoms. Efforts to prevent bites include the use of DEET or picaridin - based insect repellent , covering much of the body with clothing, mosquito nets , and getting rid of standing water where mosquitoes reproduce. There is no vaccine . Health officials recommended that women in areas affected by the 2015–2016 Zika outbreak consider putting off pregnancy and that pregnant women not travel to these areas. While no specific treatment exists, paracetamol (acetaminophen) and rest may help with the symptoms. Admission to a hospital is rarely necessary. It is advised, for an affected person with the zika virus, to drink a lot of water to stay hydrated, to lie down, and to treat the fever and agony with liquid solutions; taking drugs like acetaminophen or paracetamol helps to relieve fever and pain. [ according to whom? ] Referring to the US CDC it is not recommended to take anti-inflammatory and non-steroid drugs like aspirin for example. If the patient affected is already taking treatment for another medical condition it is advisable to inform your attending physician before taking any other drug or additional treatment; The World Health Organization has suggested that priority should be to develop inactivated vaccines and other nonlive vaccines, which are safe to use in pregnant women. As of March 2016 [ update ] , 18 companies and institutions were developing vaccines against Zika, but they state a vaccine is unlikely to be widely available for about 10 years. In June 2016, the FDA granted the first approval for a human clinical trial for a Zika vaccine. In March 2017, a DNA vaccine was approved for phase-2 clinical trials. This vaccine consists of a small, circular piece of DNA, known as a plasmid, that expresses the genes for the Zika virus envelope proteins. As the vaccine does not contain the full sequence of the virus, it cannot cause infection. As of April 2017, both subunit and inactivated vaccines have entered clinical trials. It is advised, for an affected person with the zika virus, to drink a lot of water to stay hydrated, to lie down, and to treat the fever and agony with liquid solutions; taking drugs like acetaminophen or paracetamol helps to relieve fever and pain. [ according to whom? ] Referring to the US CDC it is not recommended to take anti-inflammatory and non-steroid drugs like aspirin for example. If the patient affected is already taking treatment for another medical condition it is advisable to inform your attending physician before taking any other drug or additional treatment; The World Health Organization has suggested that priority should be to develop inactivated vaccines and other nonlive vaccines, which are safe to use in pregnant women. As of March 2016 [ update ] , 18 companies and institutions were developing vaccines against Zika, but they state a vaccine is unlikely to be widely available for about 10 years. In June 2016, the FDA granted the first approval for a human clinical trial for a Zika vaccine. In March 2017, a DNA vaccine was approved for phase-2 clinical trials. This vaccine consists of a small, circular piece of DNA, known as a plasmid, that expresses the genes for the Zika virus envelope proteins. As the vaccine does not contain the full sequence of the virus, it cannot cause infection. As of April 2017, both subunit and inactivated vaccines have entered clinical trials. The virus was first isolated in April 1947 from a rhesus macaque monkey placed in a cage in the Ziika Forest of Uganda , near Lake Victoria , by the scientists of the Yellow Fever Research Institute . A second isolation from the mosquito A. africanus followed at the same site in January 1948. When the monkey developed a fever, researchers isolated from its serum a "filterable transmissible agent" which was named Zika in 1948. Zika was first known to infect humans from the results of a serological survey in Uganda, published in 1952. Of 99 human blood samples tested, 6.1% had neutralizing antibodies. As part of a 1954 outbreak investigation of jaundice suspected to be yellow fever, researchers reported isolation of the virus from a patient, but the pathogen was later shown to be the closely related Spondweni virus . Spondweni was also determined to be the cause of a self-inflicted infection in a researcher reported in 1956. Subsequent serological studies in several African and Asian countries indicated the virus had been widespread within human populations in these regions. The first true case of human infection was identified by Simpson in 1964, who was himself infected while isolating the virus from mosquitoes. From then until 2007, there were only 13 further confirmed human cases of Zika infection from Africa and Southeast Asia. A study published in 2017 showed that the Zika virus, despite only a few cases were reported, has been silently circulated in West Africa for the last two decades when blood samples collected between 1992 and 2016 were tested for the ZIKV IgM antibodies. In 2017, Angola reported two cases of Zika fever. Zika was also occurring in Tanzania as of 2016. In April 2007, the first outbreak outside of Africa and Asia occurred on the island of Yap in the Federated States of Micronesia, characterized by rash, conjunctivitis, and arthralgia, which was initially thought to be dengue, chikungunya , or Ross River disease . Serum samples from patients in the acute phase of illness contained RNA of Zika. There were 49 confirmed cases, 59 unconfirmed cases, no hospitalizations, and no deaths. After October 2013 Oceania's first outbreak showed an estimated 11% population infected for French Polynesia that also presented with Guillain–Barre syndrome (GBS). The spread of ZIKV continued to New Caledonia, Easter Island, and the Cook Islands and where 1385 cases were confirmed by January 2014. During the same year, Easter Island acknowledged 51 cases. Australia began seeing cases in 2012. Research showed it was brought by travelers returning from Indonesia and other infected countries. New Zealand also experienced infections rate increases through returning foreign travelers. Oceania countries experiencing Zika today are New Caledonia, Vanuatu, Solomon Islands, Marshall Islands, American Samoa, Samoa, and Tonga. Between 2013 and 2014, further epidemics occurred in French Polynesia , Easter Island , the Cook Islands , and New Caledonia . There was an epidemic in 2015 and 2016 in the Americas . The outbreak began in April 2015 in Brazil , and spread to other countries in South America , Central America , North America , and the Caribbean . In January 2016, the WHO said the virus was likely to spread throughout most of the Americas by the end of the year; and in February 2016, the WHO declared the cluster of microcephaly and Guillain–Barré syndrome cases reported in Brazil – strongly suspected to be associated with the Zika outbreak – a Public Health Emergency of International Concern . It was estimated that 1.5 million people were infected by Zika in Brazil, with over 3,500 cases of microcephaly reported between October 2015 and January 2016. A number of countries issued travel warnings , and the outbreak was expected to significantly impact the tourism industry. Several countries have taken the unusual step of advising their citizens to delay pregnancy until more is known about the virus and its impact on fetal development. With the 2016 Summer Olympics hosted in Rio de Janeiro , health officials worldwide voiced concerns over a potential crisis, both in Brazil and when international athletes and tourists returned home and possibly would spread the virus. Some researchers speculated that only one or two tourists might be infected during the three-week period, or approximately 3.2 infections per 100,000 tourists. In November 2016, the World Health Organization declared that Zika virus was no longer a global emergency while noting that the virus still represents "a highly significant and a long-term problem". As of August 2017 the number of new Zika virus cases in the Americas had fallen dramatically. On May 15, 2017, three cases of Zika virus infection in India were reported in the state of Gujarat . By late 2018, there had been at least 159 cases in Rajasthan and 127 in Madhya Pradesh . In July 2021, the first case of Zika virus infection in the Indian state of Kerala was reported. After the first confirmed case, 19 other people who had previously presented symptoms were tested, and 13 of those had positive results, showing that Zika had been circulating in Kerala since at least May 2021. By August 6th 2021, there had been 65 reported cases in Kerala. On October 22, 2021, an officer in the Indian Air Force in Kanpur tested positive for Zika virus, making it the first reported case in the Indian state of Uttar Pradesh . On 22 March 2016, Reuters reported that Zika was isolated from a 2014 blood sample of an elderly man in Chittagong in Bangladesh as part of a retrospective study . Between August and November 2016, 455 cases of Zika virus infection were confirmed in Singapore . In 2023, 722 Zika virus cases were reported in Thailand. From 2019-2022 the Robert Koch-Institut reported 29 imported Zikavirus cases imported into Germany. Of the altogether 16 imported Zika virus cases in 2023, 10 were diagnosed after a trip to Thailand with 62% of all Zika virus cases a significant relative and absolute increase. The virus was first isolated in April 1947 from a rhesus macaque monkey placed in a cage in the Ziika Forest of Uganda , near Lake Victoria , by the scientists of the Yellow Fever Research Institute . A second isolation from the mosquito A. africanus followed at the same site in January 1948. When the monkey developed a fever, researchers isolated from its serum a "filterable transmissible agent" which was named Zika in 1948. Zika was first known to infect humans from the results of a serological survey in Uganda, published in 1952. Of 99 human blood samples tested, 6.1% had neutralizing antibodies. As part of a 1954 outbreak investigation of jaundice suspected to be yellow fever, researchers reported isolation of the virus from a patient, but the pathogen was later shown to be the closely related Spondweni virus . Spondweni was also determined to be the cause of a self-inflicted infection in a researcher reported in 1956. Subsequent serological studies in several African and Asian countries indicated the virus had been widespread within human populations in these regions. The first true case of human infection was identified by Simpson in 1964, who was himself infected while isolating the virus from mosquitoes. From then until 2007, there were only 13 further confirmed human cases of Zika infection from Africa and Southeast Asia. A study published in 2017 showed that the Zika virus, despite only a few cases were reported, has been silently circulated in West Africa for the last two decades when blood samples collected between 1992 and 2016 were tested for the ZIKV IgM antibodies. In 2017, Angola reported two cases of Zika fever. Zika was also occurring in Tanzania as of 2016. In April 2007, the first outbreak outside of Africa and Asia occurred on the island of Yap in the Federated States of Micronesia, characterized by rash, conjunctivitis, and arthralgia, which was initially thought to be dengue, chikungunya , or Ross River disease . Serum samples from patients in the acute phase of illness contained RNA of Zika. There were 49 confirmed cases, 59 unconfirmed cases, no hospitalizations, and no deaths. After October 2013 Oceania's first outbreak showed an estimated 11% population infected for French Polynesia that also presented with Guillain–Barre syndrome (GBS). The spread of ZIKV continued to New Caledonia, Easter Island, and the Cook Islands and where 1385 cases were confirmed by January 2014. During the same year, Easter Island acknowledged 51 cases. Australia began seeing cases in 2012. Research showed it was brought by travelers returning from Indonesia and other infected countries. New Zealand also experienced infections rate increases through returning foreign travelers. Oceania countries experiencing Zika today are New Caledonia, Vanuatu, Solomon Islands, Marshall Islands, American Samoa, Samoa, and Tonga. Between 2013 and 2014, further epidemics occurred in French Polynesia , Easter Island , the Cook Islands , and New Caledonia . There was an epidemic in 2015 and 2016 in the Americas . The outbreak began in April 2015 in Brazil , and spread to other countries in South America , Central America , North America , and the Caribbean . In January 2016, the WHO said the virus was likely to spread throughout most of the Americas by the end of the year; and in February 2016, the WHO declared the cluster of microcephaly and Guillain–Barré syndrome cases reported in Brazil – strongly suspected to be associated with the Zika outbreak – a Public Health Emergency of International Concern . It was estimated that 1.5 million people were infected by Zika in Brazil, with over 3,500 cases of microcephaly reported between October 2015 and January 2016. A number of countries issued travel warnings , and the outbreak was expected to significantly impact the tourism industry. Several countries have taken the unusual step of advising their citizens to delay pregnancy until more is known about the virus and its impact on fetal development. With the 2016 Summer Olympics hosted in Rio de Janeiro , health officials worldwide voiced concerns over a potential crisis, both in Brazil and when international athletes and tourists returned home and possibly would spread the virus. Some researchers speculated that only one or two tourists might be infected during the three-week period, or approximately 3.2 infections per 100,000 tourists. In November 2016, the World Health Organization declared that Zika virus was no longer a global emergency while noting that the virus still represents "a highly significant and a long-term problem". As of August 2017 the number of new Zika virus cases in the Americas had fallen dramatically. On May 15, 2017, three cases of Zika virus infection in India were reported in the state of Gujarat . By late 2018, there had been at least 159 cases in Rajasthan and 127 in Madhya Pradesh . In July 2021, the first case of Zika virus infection in the Indian state of Kerala was reported. After the first confirmed case, 19 other people who had previously presented symptoms were tested, and 13 of those had positive results, showing that Zika had been circulating in Kerala since at least May 2021. By August 6th 2021, there had been 65 reported cases in Kerala. On October 22, 2021, an officer in the Indian Air Force in Kanpur tested positive for Zika virus, making it the first reported case in the Indian state of Uttar Pradesh . On 22 March 2016, Reuters reported that Zika was isolated from a 2014 blood sample of an elderly man in Chittagong in Bangladesh as part of a retrospective study . Between August and November 2016, 455 cases of Zika virus infection were confirmed in Singapore . In 2023, 722 Zika virus cases were reported in Thailand. From 2019-2022 the Robert Koch-Institut reported 29 imported Zikavirus cases imported into Germany. Of the altogether 16 imported Zika virus cases in 2023, 10 were diagnosed after a trip to Thailand with 62% of all Zika virus cases a significant relative and absolute increase.

Wiki

Chikungunya

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

Crisis in Venezuela

GPPSB MUD / AD / PU Hugo Chávez †Nicolás Maduro Diosdado Cabello Delcy Rodríguez Tareck El Aissami Leopoldo López Juan Guaidó Henrique Capriles Henry Ramos Allup Julio Borges An ongoing socioeconomic and political crisis began in Venezuela during the presidency of Hugo Chávez and has worsened during the presidency of his successor Nicolás Maduro . It has been marked by hyperinflation , escalating starvation, disease, crime and mortality rates, resulting in massive emigration from the country. The situation is believed to be by far the worst economic crisis in Venezuela's history, and is also the worst facing a country in peacetime since the mid-20th century. The crisis is often considered to be more severe than that of the United States during the Great Depression , the 1985–1994 Brazilian economic crisis , or the 2008–2009 hyperinflation in Zimbabwe . Other writers have also compared aspects of the crisis, such as unemployment and GDP contraction, to that of Bosnia and Herzegovina after the 1992–1995 Bosnian War , and those in Russia , Cuba and Albania following the collapse of the Eastern Bloc in 1989 and the dissolution of the Soviet Union in 1991. On 2 June 2010, Chávez declared an "economic war" due to increasing shortages in Venezuela . The crisis intensified under the Maduro government, growing more severe as a result of low oil prices in early 2015 , and a drop in Venezuela's oil production from lack of maintenance and investment. In January 2016, the opposition-led National Assembly declared a "health humanitarian crisis". The government failed to cut spending in the face of falling oil revenues, and has dealt with the crisis by denying its existence, as well as violently repressing opposition . Extrajudicial killings by the Venezuelan government became common, with the United Nations (UN) reporting 5,287 killings by the Special Action Forces in 2017, with at least another 1,569 killings recorded in the first six months of 2019, stating that some of the killings were "done as a reprisal for [the victims'] participation in anti-government demonstrations." Political corruption , chronic shortages of food and medicine, closure of businesses, unemployment, deterioration of productivity, authoritarianism , human rights violations , gross economic mismanagement and high dependence on oil have also contributed to the worsening crisis. As a response to human rights abuses, the degradation in the rule of law, and corruption, the European Union , the Lima Group , the United States and other countries have applied individual sanctions against government officials and members of both the military and security forces. The United States would later extend its sanctions to the petroleum sector. Supporters of Chávez and Maduro said that the problems result from an "economic war" on Venezuela, falling oil prices, international sanctions , and the country's business elite, while critics of the government say the cause is years of economic mismanagement and corruption. Most observers cite anti-democratic governance, corruption, and mismanagement of the economy as causes of the crisis. Others attribute the crisis to the " socialist ", " populist ", or "hyper-populist" nature of the government's policies, and the use of these policies to maintain political power. National and international analysts and economists stated that the crisis is not the result of a conflict, natural disaster, or sanctions, but rather of the consequences of populist policies and corrupt practices that began under the Chávez administration's Bolivarian Revolution and continued under the Maduro administration. The crisis has affected the life of the average Venezuelan on all levels. By 2017, hunger had escalated to the point where almost seventy-five percent of the population had lost an average of over 8 kg (over 19 lbs) in weight [lower-alpha 1] and more than half did not have enough income to meet their basic food needs. A UN report estimated in March 2019 that 94% of Venezuelans lived in poverty, and by 2021 almost twenty percent of Venezuelans (5.4 million) had left their country. The UN analysis estimates in 2019 that 25% of Venezuelans need some form of humanitarian assistance. Venezuela led the world in murder rates , with 81.4 per 100,000 people killed in 2018, making it the third most violent country in the world. Following increased international sanctions throughout 2019, the Maduro government abandoned policies established by Chávez such as price and currency controls, which resulted in the country seeing a temporary rebound from economic decline before COVID-19 entered Venezuela the following year. As a response to the devaluation of the official bolívar currency , by 2019 the population increasingly started relying on US dollars for transactions. According to the national Living Conditions Survey (ENCOVI), by 2021 94.5% of the population was living in poverty based on income, out of which 76.6% lived under extreme poverty, the highest figure ever recorded in the country. In 2022, after the implementation of mild economic liberalization , poverty decreased in Venezuela and the country's economy grew for the first time in eight years. Despite these improvements, Venezuela continues to have the highest rate of inequality in the Americas. Although food shortages and hyperinflation have largely ended, inflation remains high in Venezuela. After attempting a coup d'état in 1992 and being pardoned by President Rafael Caldera , Hugo Chávez was elected president and maintained the presidency from 1999 until his death in 2013. Increasing oil prices in the early 2000s led to levels of funds not seen in Venezuela since the 1980s. Chávez established Bolivarian missions , aimed at providing public services to improve economic, cultural, and social conditions. According to Corrales and Penfold, "aid was disbursed to some of the poor and, more gravely, in a way that ended up helping the president and his allies and cronies more than anyone else". Nonetheless, poverty was cut more than 20 percent between 2002 and 2008. The Missions entailed the construction of thousands of free medical clinics for the poor, and the enactment of food and housing subsidies. A 2010 OAS report indicated achievements in addressing illiteracy, healthcare and poverty, and economic and social advances. The quality of life for Venezuelans had also improved according to a UN Index. Teresa A. Meade wrote that Chávez's popularity strongly depended "on the lower classes who have benefited from these health initiatives and similar policies." According to Chosun Ilbo , Venezuela began to face economic difficulties due to Chávez's populist policies. On 2 June 2010, Chávez declared an "economic war" due to increasing shortages in Venezuela . Political corruption , chronic shortages of food and medicine, closure of businesses, unemployment, deterioration of productivity, authoritarianism , human rights violations , gross economic mismanagement and high dependence on oil have also contributed to the worsening crisis. The social works initiated by Chávez's government relied on oil products , the keystone of the Venezuelan economy, leading to Dutch disease according to Javier Corrales. [lower-alpha 2] By the early 2010s, economic actions taken by Chávez's government during the preceding decade, such as overspending and price controls, became unsustainable. Venezuela's economy faltered while poverty , inflation and shortages in Venezuela increased. According to Martinez Lázaro, professor of economics at the IE Business School in Madrid, the economic woes Venezuela continued to suffer under Maduro would have occurred even if Chávez were still in power. In early 2013, shortly after Chávez's death, Foreign Policy stated that whoever succeeded Chávez would "inherit one of the most dysfunctional economies in the Americas—and just as the bill for the deceased leader's policies comes due." Following Chávez's death in 2013, Nicolás Maduro became president after defeating his opponent Henrique Capriles Radonski by 235,000 votes, a 1.5% margin. Maduro continued most of the existing economic policies of his predecessor Chávez . Upon entering the presidency, his administration faced a high inflation rate and large shortages of goods, problems left over from Chávez's policies. Maduro said capitalist speculation had driven high rates of inflation and created widespread shortages of basic necessities. He enacted economic measures against political opponents, who he and loyalists stated were behind an international economic conspiracy. [ clarification needed ] Maduro was criticized [ by whom? ] for concentrating on public opinion, instead of tending to practical issues which economists had warned about, or creating ideas to improve Venezuela's economic prospects. By 2014, Venezuela had entered an economic recession and by 2016, the country had an inflation rate of 800%, the highest in its history. The crisis intensified under the Maduro government, growing more severe as a result of low oil prices in early 2015 , and a drop in Venezuela's oil production from lack of maintenance and investment. The government failed to cut spending in the face of falling oil revenues, and has dealt with the crisis by denying its existence and violently repressing opposition. Extrajudicial killings by the Venezuelan government became common, with the United Nations (UN) reporting 5,287 killings by the Special Action Forces (FAES) in 2017, with at least another 1,569 killings recorded in the first six months of 2019; the UN had "reasonable grounds to believe that many of these killings constitute extrajudicial executions" and characterized the security operations as "aimed at neutralizing, repressing and criminalizing political opponents and people critical of the government". The UN also stated that the Special Action Forces "would plant arms and drugs and fire their weapons against the walls or in the air to suggest a confrontation and to show the victim had resisted authority" and that some of the killings were "done as a reprisal for [the victims'] participation in anti-government demonstrations." In January 2016, the National Assembly declared a "health humanitarian crisis" given the "serious shortage of medicines, medical supplies and deterioration of humanitarian infrastructure", asking Maduro's government to "guarantee immediate access to the list of essential medicines that are basic and indispensable and that must be accessible at all times." In August, Secretary-General of the United Nations Ban Ki-moon declared that there was a humanitarian crisis in Venezuela caused by the lack of basic needs, including food, water, sanitation and clothing. Before the 2019 presidential crisis , the Maduro government denied several offers of aid, stating that there was not a humanitarian crisis and that such claims were used to justify foreign intervention. Maduro's refusal of aid worsened the effects of Venezuela's crisis. In March 2019, The Wall Street Journal said that "Mr. Maduro has long used food and other government handouts to pressure impoverished Venezuelans to attend pro-government rallies and to support him during elections as the country's economic meltdown has intensified." In 2019, The Economist wrote that the Maduro government had obtained "extra money from selling gold (both from illegal mines and from its reserves) and narcotics". Since 2010, Venezuela has been suffering a socioeconomic crisis under Maduro, and briefly under his predecessor, Chávez. As a result of discontent with the government, in the 2015 parliamentary election the opposition was elected to the majority in the National Assembly , after which the outgoing ( lame duck ) National Assembly—consisting of Bolivarian officials—filled the Supreme Tribunal of Justice , the highest court in Venezuela, with Maduro allies. Maduro disavowed the National Assembly in 2017 leading to the 2017 Venezuelan constitutional crisis ; as of 2018, some considered the National Assembly the only "legitimate" institution left in the country, [lower-alpha 3] and human rights organizations said there were no independent institutional checks on presidential power. [lower-alpha 4] Following the constitutional crisis and the push to ban opposition presidential candidate Henrique Capriles from politics for 15 years, protests grew to their most "combative" since they began in 2014. During the protests, the Mother of all Protests involved between 2.5 million and 6 million protesters. On 1 May 2017 following a month of protests that resulted in at least 29 dead, Maduro called for a constituent assembly that would draft a new constitution to replace the 1999 Venezuela Constitution created under Chávez. He invoked Article 347, and stated that his call for a new constitution was necessary to counter the actions of the opposition. The members of the Constituent Assembly would not be elected in open elections, but selected from social organizations loyal to Maduro. It would also allow him to stay in power during the interregnum and skip the 2018 presidential elections , as the process would take at least two years. Many countries considered these actions a bid by Maduro to stay in power indefinitely, and over 40 countries stated that they would not recognize the 2017 Constituent National Assembly (ANC), along with supranational bodies such as the European Union , Mercosur and the OAS. The Democratic Unity Roundtable — the opposition to the incumbent ruling party — boycotted the election, saying that the ANC was "a trick to keep [the incumbent ruling party] in power". Since the opposition did not participate in the election, the incumbent Great Patriotic Pole , dominated by the United Socialist Party of Venezuela , won almost all seats in the assembly by default. Maduro's allies—such as Bolivia , El Salvador , Cuba , Nicaragua , Russia and Syria —discouraged foreign intervention in Venezuelan politics and congratulated the president. The ANC was sworn in on 4 August 2017, and the next day declared itself to be the government branch with supreme power in Venezuela, banning the opposition-led National Assembly from performing actions that would interfere with the assembly while continuing to pass measures in "support and solidarity" with President Maduro, effectively stripping the National Assembly of all its powers. In February 2018 Maduro called presidential elections, four months before the prescribed date. There were many irregularities, including the banning from standing of several major opposition parties. Maduro was declared the winner in May 2018. Many said the elections were invalid. Politicians both internally and internationally said Maduro was not legitimately elected, and considered him an ineffective dictator. In the months leading up to his 10 January 2019 inauguration, Maduro was pressured to step down by nations and bodies including the Lima Group (excluding Mexico), the United States, and the OAS; this pressure was increased after the new National Assembly of Venezuela was sworn in on 5 January 2019. The 2019 presidential crisis came to a head when the National Assembly stated that the results of the May 2018 presidential election were invalid and declared National Assembly president Juan Guaidó to be the acting president, citing several clauses of the 1999 Venezuelan Constitution . Corruption is high in Venezuela according to the Transparency International Corruption Perceptions Index and is prevalent at many levels of society. While corruption is difficult to measure reliably, in 2018 Transparency International ranked Venezuela among the top 13 most corrupt countries out of 180 measured, tied with Iraq , but ahead of Afghanistan , Burundi , Equatorial Guinea , Guinea , North Korea , Libya , Somalia , South Sudan , Sudan , Syria and Yemen . A 2016 poll found that 73% of Venezuelans believed their police were corrupt. Latinobarómetro 's 2018 report said that 65% of Venezuelans believed their president was involved in corruption, and 64% believed that government officials were corrupt. Discontent with corruption was cited by opposition-aligned groups as one of the reasons for the 2014 Venezuelan protests . A once wealthy country, Venezuela's economy was driven into political and economic crisis by corruption and mismanagement. After attempting a coup d'état in 1992 and being pardoned by President Rafael Caldera , Hugo Chávez was elected president and maintained the presidency from 1999 until his death in 2013. Increasing oil prices in the early 2000s led to levels of funds not seen in Venezuela since the 1980s. Chávez established Bolivarian missions , aimed at providing public services to improve economic, cultural, and social conditions. According to Corrales and Penfold, "aid was disbursed to some of the poor and, more gravely, in a way that ended up helping the president and his allies and cronies more than anyone else". Nonetheless, poverty was cut more than 20 percent between 2002 and 2008. The Missions entailed the construction of thousands of free medical clinics for the poor, and the enactment of food and housing subsidies. A 2010 OAS report indicated achievements in addressing illiteracy, healthcare and poverty, and economic and social advances. The quality of life for Venezuelans had also improved according to a UN Index. Teresa A. Meade wrote that Chávez's popularity strongly depended "on the lower classes who have benefited from these health initiatives and similar policies." According to Chosun Ilbo , Venezuela began to face economic difficulties due to Chávez's populist policies. On 2 June 2010, Chávez declared an "economic war" due to increasing shortages in Venezuela . Political corruption , chronic shortages of food and medicine, closure of businesses, unemployment, deterioration of productivity, authoritarianism , human rights violations , gross economic mismanagement and high dependence on oil have also contributed to the worsening crisis. The social works initiated by Chávez's government relied on oil products , the keystone of the Venezuelan economy, leading to Dutch disease according to Javier Corrales. [lower-alpha 2] By the early 2010s, economic actions taken by Chávez's government during the preceding decade, such as overspending and price controls, became unsustainable. Venezuela's economy faltered while poverty , inflation and shortages in Venezuela increased. According to Martinez Lázaro, professor of economics at the IE Business School in Madrid, the economic woes Venezuela continued to suffer under Maduro would have occurred even if Chávez were still in power. In early 2013, shortly after Chávez's death, Foreign Policy stated that whoever succeeded Chávez would "inherit one of the most dysfunctional economies in the Americas—and just as the bill for the deceased leader's policies comes due." Following Chávez's death in 2013, Nicolás Maduro became president after defeating his opponent Henrique Capriles Radonski by 235,000 votes, a 1.5% margin. Maduro continued most of the existing economic policies of his predecessor Chávez . Upon entering the presidency, his administration faced a high inflation rate and large shortages of goods, problems left over from Chávez's policies. Maduro said capitalist speculation had driven high rates of inflation and created widespread shortages of basic necessities. He enacted economic measures against political opponents, who he and loyalists stated were behind an international economic conspiracy. [ clarification needed ] Maduro was criticized [ by whom? ] for concentrating on public opinion, instead of tending to practical issues which economists had warned about, or creating ideas to improve Venezuela's economic prospects. By 2014, Venezuela had entered an economic recession and by 2016, the country had an inflation rate of 800%, the highest in its history. The crisis intensified under the Maduro government, growing more severe as a result of low oil prices in early 2015 , and a drop in Venezuela's oil production from lack of maintenance and investment. The government failed to cut spending in the face of falling oil revenues, and has dealt with the crisis by denying its existence and violently repressing opposition. Extrajudicial killings by the Venezuelan government became common, with the United Nations (UN) reporting 5,287 killings by the Special Action Forces (FAES) in 2017, with at least another 1,569 killings recorded in the first six months of 2019; the UN had "reasonable grounds to believe that many of these killings constitute extrajudicial executions" and characterized the security operations as "aimed at neutralizing, repressing and criminalizing political opponents and people critical of the government". The UN also stated that the Special Action Forces "would plant arms and drugs and fire their weapons against the walls or in the air to suggest a confrontation and to show the victim had resisted authority" and that some of the killings were "done as a reprisal for [the victims'] participation in anti-government demonstrations." In January 2016, the National Assembly declared a "health humanitarian crisis" given the "serious shortage of medicines, medical supplies and deterioration of humanitarian infrastructure", asking Maduro's government to "guarantee immediate access to the list of essential medicines that are basic and indispensable and that must be accessible at all times." In August, Secretary-General of the United Nations Ban Ki-moon declared that there was a humanitarian crisis in Venezuela caused by the lack of basic needs, including food, water, sanitation and clothing. Before the 2019 presidential crisis , the Maduro government denied several offers of aid, stating that there was not a humanitarian crisis and that such claims were used to justify foreign intervention. Maduro's refusal of aid worsened the effects of Venezuela's crisis. In March 2019, The Wall Street Journal said that "Mr. Maduro has long used food and other government handouts to pressure impoverished Venezuelans to attend pro-government rallies and to support him during elections as the country's economic meltdown has intensified." In 2019, The Economist wrote that the Maduro government had obtained "extra money from selling gold (both from illegal mines and from its reserves) and narcotics". Since 2010, Venezuela has been suffering a socioeconomic crisis under Maduro, and briefly under his predecessor, Chávez. As a result of discontent with the government, in the 2015 parliamentary election the opposition was elected to the majority in the National Assembly , after which the outgoing ( lame duck ) National Assembly—consisting of Bolivarian officials—filled the Supreme Tribunal of Justice , the highest court in Venezuela, with Maduro allies. Maduro disavowed the National Assembly in 2017 leading to the 2017 Venezuelan constitutional crisis ; as of 2018, some considered the National Assembly the only "legitimate" institution left in the country, [lower-alpha 3] and human rights organizations said there were no independent institutional checks on presidential power. [lower-alpha 4] Following the constitutional crisis and the push to ban opposition presidential candidate Henrique Capriles from politics for 15 years, protests grew to their most "combative" since they began in 2014. During the protests, the Mother of all Protests involved between 2.5 million and 6 million protesters. On 1 May 2017 following a month of protests that resulted in at least 29 dead, Maduro called for a constituent assembly that would draft a new constitution to replace the 1999 Venezuela Constitution created under Chávez. He invoked Article 347, and stated that his call for a new constitution was necessary to counter the actions of the opposition. The members of the Constituent Assembly would not be elected in open elections, but selected from social organizations loyal to Maduro. It would also allow him to stay in power during the interregnum and skip the 2018 presidential elections , as the process would take at least two years. Many countries considered these actions a bid by Maduro to stay in power indefinitely, and over 40 countries stated that they would not recognize the 2017 Constituent National Assembly (ANC), along with supranational bodies such as the European Union , Mercosur and the OAS. The Democratic Unity Roundtable — the opposition to the incumbent ruling party — boycotted the election, saying that the ANC was "a trick to keep [the incumbent ruling party] in power". Since the opposition did not participate in the election, the incumbent Great Patriotic Pole , dominated by the United Socialist Party of Venezuela , won almost all seats in the assembly by default. Maduro's allies—such as Bolivia , El Salvador , Cuba , Nicaragua , Russia and Syria —discouraged foreign intervention in Venezuelan politics and congratulated the president. The ANC was sworn in on 4 August 2017, and the next day declared itself to be the government branch with supreme power in Venezuela, banning the opposition-led National Assembly from performing actions that would interfere with the assembly while continuing to pass measures in "support and solidarity" with President Maduro, effectively stripping the National Assembly of all its powers. In February 2018 Maduro called presidential elections, four months before the prescribed date. There were many irregularities, including the banning from standing of several major opposition parties. Maduro was declared the winner in May 2018. Many said the elections were invalid. Politicians both internally and internationally said Maduro was not legitimately elected, and considered him an ineffective dictator. In the months leading up to his 10 January 2019 inauguration, Maduro was pressured to step down by nations and bodies including the Lima Group (excluding Mexico), the United States, and the OAS; this pressure was increased after the new National Assembly of Venezuela was sworn in on 5 January 2019. The 2019 presidential crisis came to a head when the National Assembly stated that the results of the May 2018 presidential election were invalid and declared National Assembly president Juan Guaidó to be the acting president, citing several clauses of the 1999 Venezuelan Constitution . Corruption is high in Venezuela according to the Transparency International Corruption Perceptions Index and is prevalent at many levels of society. While corruption is difficult to measure reliably, in 2018 Transparency International ranked Venezuela among the top 13 most corrupt countries out of 180 measured, tied with Iraq , but ahead of Afghanistan , Burundi , Equatorial Guinea , Guinea , North Korea , Libya , Somalia , South Sudan , Sudan , Syria and Yemen . A 2016 poll found that 73% of Venezuelans believed their police were corrupt. Latinobarómetro 's 2018 report said that 65% of Venezuelans believed their president was involved in corruption, and 64% believed that government officials were corrupt. Discontent with corruption was cited by opposition-aligned groups as one of the reasons for the 2014 Venezuelan protests . A once wealthy country, Venezuela's economy was driven into political and economic crisis by corruption and mismanagement. The Wall Street Journal reported in March 2019 that poverty was double that of 2014. A study from Andrés Bello Catholic University indicated that by 2019 at least 8 million Venezuelans did not have enough to eat. A UN report estimated in March 2019 that 94% of Venezuelans live in poverty, and that one quarter of Venezuelans need some form of humanitarian assistance . According to the Living Conditions Survey by the Andrés Bello Catholic University (Encovi in Spanish, Encuesta de Condiciones de Vida ), by 2021 94.5% of the population was in poverty based on income, out of which 76.6% lived under extreme poverty, the highest figure ever recorded in the country. More than 70% of Venezuela's food is imported; Venezuela became so dependent on food imports that it could no longer afford when the price of oil dropped in 2014. Chávez gave the military control of food, and nationalized much of the industry, which was then neglected, leading to production shortages. With a "diminished food supply", Maduro put "generals in charge of everything from butter to rice". With the military in charge of food, food trafficking became profitable, bribes and corruption common, and food did not reach the needy. The government imports most of the food the country needs, it is controlled by the military, and the price paid for food is higher than justified by market prices. Venezuelans were spending "all day waiting in lines" to buy rationed food, "pediatric wards filled up with underweight children, and formerly middle-class adults began picking through rubbish bins for scraps". Several other factors have led to shortages: imports over the two years until the end of 2017 declined by two-thirds; hyperinflation has made food too costly for many Venezuelans; and for those who depend on food boxes supplied by the government, "these do not reach all Venezuelans who need them, provision of boxes is intermittent, and receipt is often linked to political support of the government". Corruption became a problem in the distribution of food. The operations director at one food import business says "he pays off a long roster of military officials for each shipment of food he brings in from ... the US. It's an unbroken chain of bribery from when your ship comes in until the food is driven out in trucks." A National Guard lieutenant denies this charge, saying corruption would be worse if the military were not involved; government and military officials say the opposition is overstating the corruption problem for their own benefit. Retired General Antonio Rivero said that "Maduro is trying to prevent soldiers from going hungry and being tempted to participate in an uprising against an increasingly unpopular government", adding that using the military to control food distribution has "drained the feeling of rebellion from the armed forces" by giving soldiers access to food denied others, with the resulting corruption increasing shortages for the general public. The colectivos are also involved in food trafficking, selling food on the black market; a colectivo leader told InSight Crime that trafficking food and medicine is as profitable as drug-running, but carries less risk. With shadowy connections to the government, The Washington Post says "some have been put in charge of the distribution of government food packages in poor areas—giving them control over hungry neighborhoods." The Associated Press reports that people gather every evening in downtown Caracas in search of food thrown out on a sidewalk; the people are typically unemployed, but are "frequently joined by small business owners, college students and pensioners—people who consider themselves middle class even though their living standards have long ago been pulverized by triple-digit inflation, food shortages and a collapsing currency". A waste collection official in Maracaibo reported that most of the trash bags he received had been gone through by people searching for food. One dump reports finding parts of dismembered animals, like "dogs, cats, donkeys, horses and pigeons" and there is evidence that people are eating wildlife such as anteaters, flamingos, vultures and lizards. "Hunger, malnutrition, and severe food shortages are widespread in all Venezuela", according to Human Rights Watch. Doctors at 21 public hospitals in 17 Venezuelan states told The New York Times in 2017 that "their emergency rooms were being overwhelmed by children with severe malnutrition—a condition they had rarely encountered before the economic crisis began", and that "hundreds have died". The government has responded with "a near-total blackout of health statistics, and by creating a culture in which doctors are often afraid to register cases and deaths that may be associated with the government's failures". The Food and Agriculture Organization of the UN said that less than 5% of Venezuelans were undernourished between 2008 and 2013, but that number had more than doubled, to almost 12% from 2015 and 2017, representing 3.7 million people. A 2016 survey found that almost three-quarters of the population said that, because of improper nutrition, they had lost on average 8.7 kg (19.4 lbs) and 64% said they lost 11 kg (24 lbs) in 2017. A 2016 Venebarometro poll of 1,200 Venezuelans found almost half are no longer able to eat three daily meals; the government blames this on an "economic war" they say is waged by the opposition. A UN report said that because of lack of water and sanitation, 4.3 million Venezuelans needed assistance in 2019. During the 2019 Venezuelan blackouts which started on 7 March, the water distribution system also had shortages. José de Viana, an engineer and former president of Hidrocapital, the municipal water company in Caracas , said that 90% of the thermoelectric plants that work as a backup if power fails are not operational because of lack of maintenance, or they have been simply disconnected, and that "the most important population centers in the country [had] zero water supply for more than four days". Analysts said that two-thirds of Venezuela's population (20 million people) were without water, partially or completely, in the weeks after the blackouts. People swarmed the polluted Guaire River in the center of Caracas to fill plastic containers with contaminated water, or collected water from streams at El Ávila National Park . Others tried to catch water from the city's sewer drains. In the state of Lara people bathed in the sewers. The head of the infectious disease department at the University Hospital of Caracas , María Eugenia Landaeta said that, without access to clean water, the chance of people contracting bacterial infections increased, and that doctors had seen during the blackouts "surges in diarrhea, typhoid fever and hepatitis A ", while non-sterile water and lack of hygiene was contributing to postpartum infections . The University Hospital goes months without dependable water or power supply, and depends on water tanks and power generators. The crisis has affected the life of the average Venezuelan on all levels. By 2017, hunger had escalated to the point where almost seventy-five percent of the population had lost an average of over 8 kg (over 19 lbs) in weight [lower-alpha 5] and more than half did not have enough income to meet their basic food needs. An UN report estimated in March 2019 that 94% of Venezuelans lived in poverty, and by 2021 almost twenty percent of Venezuelans (5.4 million) had left their country. The UN analysis estimates in 2019 that 25% of Venezuelans need some form of humanitarian assistance. Venezuela led the world in murder rates , with 81.4 per 100,000 people killed in 2018, making it the third most violent country in the world. Following increased international sanctions throughout 2019, the Maduro government abandoned policies established by Chávez such as price and currency controls, which resulted in the country seeing a temporary rebound from economic decline before COVID-19 entered Venezuela the following year. As a response to the devaluation of the official bolívar currency , by 2019 the population increasingly started relying on US dollars for transactions. Maduro described dollarization as an "escape valve" that helps the recovery of the country, the spread of productive forces in the country and the economy. However, Maduro said that the Venezuelan bolívar remained as the national currency. During the Bolivarian Revolution, the government began providing free healthcare, with Cuban medical professionals providing aid. The government's failure to concentrate on healthcare and a reduction in spending on healthcare, along with unchecked government corruption resulted in avoidable deaths due to severe shortages of medical supplies and equipment, and the emigration of medical professionals to other countries. Venezuela's reliance on imported goods and the complicated exchange rates initiated under Chávez led to increasing shortages during the late 2000s and into the 2010s that affected the availability of medicines and medical equipment in the country. Associated Press says the government stopped publishing medical statistics in 2010. The Health Minister changed multiple times during Chávez's presidency. According to a high-ranking official of Venezuela's Health Ministry, the ministers were treated as scapegoats whenever issues with public health arose in Venezuela. He also said that officials of the Health Ministry engaged in corruption to enrich themselves by selling goods intended for public healthcare to others. Early in the Maduro presidency, the government could not supply enough money for medical supplies among healthcare providers, with the president of the Venezuelan Medical Federation saying that 9 of 10 large hospitals had only 7% of required supplies and private doctors reporting numbers of patients that are "impossible" to count "dying from easily treatable illnesses when Venezuela's downward economic slide accelerated after Chávez's death". Many Venezuelans died avoidable deaths with medical professionals having scarce resources and using methods that were replaced decades ago. In February 2014, doctors at the University of Caracas Medical Hospital stopped performing surgeries due to the lack of supplies, even though nearly 3,000 people required surgery. By early 2015, only 35% of hospital beds were available and 50% of operating rooms could not function due to the lack of resources. In March 2015, a Venezuelan NGO, Red de Medicos por la Salud, reported that there was a 68% shortage of surgical supplies and a 70% shortage of medicines in Venezuelan pharmacies. In 2018, the Pan American Health Organization (PAHO) reported that approximately one-third (22,000 of 66,138) of registered physicians left Venezuela as of 2014. Rosemary DiCarlo from the UN said that 40% of medical professionals had left Venezuela and supplies of medicine were at 20% of levels needed. The Venezuelan Medical Federation said that doctors were leaving the public health care system because of shortages of drugs and equipment and poor pay. In August 2015 Human Rights Watch said "We have rarely seen access to essential medicines deteriorate as quickly as it has in Venezuela except in war zones." In 2015, the government reported that a third of patients admitted to public hospitals died. The medications of individuals who die are re-distributed through small-scale and local efforts, with the help of the families of the deceased, to try to supply surviving patients. One study of 6,500 households by three of the main universities in Venezuela found that "74% of the population had lost on average nineteen pounds in 2016". In April 2017 Venezuela's health ministry reported that maternal mortality jumped by 65% in 2016 and that the number of infant deaths rose by 30%. It also said that the number of cases of malaria was up by 76%. Shortly after Minister of Health Antonieta Caporale released in 2017 this data, and health statistics showing increases in 2016 infant and maternal mortality and infectious diseases, Maduro fired her and replaced the physician with a pharmacist close to vice-president Tareck El Aissami , Luis López Chejade. The publications were removed from the Ministry's website, and no further health data has been made available, although the government had produced health bulletins for several decades. In March 2019, The Wall Street Journal reported that the "collapse of Venezuela's health system, once one of the best in Latin America, has led to a surge in infant and maternal mortality rates and a return of rare diseases that were considered all but eradicated. Health officials say malaria, yellow fever, diphtheria, dengue and tuberculosis are now spreading from Venezuela to neighboring countries as Venezuelan refugees surge over borders." The United Nations estimated in 2019 that 2.8 million Venezuelans have healthcare needs, 300,000 are at risk of dying with cancer, diabetes or HIV as they have not had access to medicine for more than a year, and preventable diseases like diphtheria, malaria, measles and tuberculosis are rising in 2019, along with hepatitis A, because of sanitation and lack of access to water. The April 2019 HRW/Johns Hopkins report showed this rise in infectious and preventable diseases, as well as increasing malnutrition, infant and maternal death, and undertreatment of HIV . Inflation and medicine shortages have meant that patients are asked to bring their own food, water and soap, and medical supplies including scalpels and syringes. In August 2019, as part of regional efforts to help Venezuelan migrants, the United States promised that it will provide thousands of doses of HIV medication to prevent the spread of HIV/AIDS and to treat those who have it. In April 2019, Human Rights Watch (HRW) and Johns Hopkins Bloomberg School of Public Health published the results of a joint, year-long research project in a report entitled "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". Combined with data from the World Health Organization (WHO), the PAHO and Venezuelan sources, the report was based on 156 interviews with Venezuelan emigrants to Colombia and Brazil, officials from relief and humanitarian organizations, Venezuelan health care professionals, and UN and government officials from Brazil and Colombia. Most of the interviews occurred in July or August 2018 in visits by the experts to the Venezuelan border towns of Cúcuta , Colombia and Boa Vista or Pacaraima , Brazil. The Washington Post stated that the HRW/Johns Hopkins report "paints an extremely grim picture of life in Venezuela, whose once-prosperous economy has imploded because of mismanagement and corruption under Maduro"; it documents rising maternal and infant death, spread of preventable diseases, food insecurity, and child malnutrition. HRW declared that the "combination of severe medicine and food shortages ... with the spread of disease ... amounts to a complex humanitarian emergency that requires a full-scale response by the United Nations secretary-general." The Washington Post states that the report describes a healthcare system that is in "utter collapse", with diseases that are preventable via vaccination spreading, and "dramatic surges" in infectious diseases once eradicated in Venezuela. The economic crisis in Venezuela started around 2010, and the health crisis followed by two years and significantly worsened in 2017, but the situation in 2019 "is even more dismal than researchers expected". Paul Spiegel, MD, who was the editor and reviewer of the report said, "Venezuela is a middle-income country with a previously strong infrastructure, so just to see this incredible decline ... in such a short period of time is quite astonishing." Alberto Paniz-Mondolfi , a doctor in Barquisimeto , Venezuela who is a member of the Venezuelan National Academy of Medicine, told NPR that the report gave an accurate, thorough and timely depiction of the medical situation in his country; he had no affiliation with the report, but said that he had seen cases where there were not even catheters for hooking up children who appeared to have malnutrition for intravenous therapy . Spiegel adds that, because of the infrastructure and trained personnel in Venezuela, aid can be distributed quickly once delivered to Venezuela. On May 16, 2018, President Maduro said that "everything [that has been said] about measles and diphtheria is a lie, we vaccinate the whole community for free" and that "with regards to food, Venezuela has unique policies, which have enabled us to carry on with a program allowing us to maintain levels of food that are necessary for the people." Days later, the undersecretary of health, Indhriana Parada, gave a speech at WHO highlighting the "achievements" of the Venezuelan health system. She said that "in Venezuela there is no humanitarian crisis" and that "Venezuela guarantees access to basic medicines to the most vulnerable groups through distribution policies." In the case of malaria, she said that government measures had "reduced incidence by 50 percent". "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". The Maduro administration does not publish health statistics, but rather it "paint[s] a rosy picture of its health care system". The Guardian reported Maduro's response to the country's health care crisis as "inadequate". "Because of the intransigence of President Nicolás Maduro—who has blamed deprivations on US sanctions and refused to allow anything beyond a trickle of assistance to enter the country"—aid has not been delivered quickly enough. Reuters reported that "Maduro says there is no crisis and no need for humanitarian aid, blaming U.S. sanctions for the country's economic problems." Venezuela's Foreign Minister Jorge Arreaza did not respond to a letter asking for Venezuela's "views regarding the extent of the crisis and the policies it was implementing to address it" before the HRW/Johns Hopkins report was published. The HRW summary of the HRW/Johns Hopkins report said, "The Venezuelan authorities during the presidency of Nicolás Maduro have proven unable to stem the crisis, and have in fact exacerbated it through their efforts to suppress information about the scale and urgency of the problems." The Associated Press said Maduro "suppress[es] information" and has made the problem worse. The Americas director for HRW, José Miguel Vivanco said, "Venezuelan authorities publicly minimise and suppress information about the crisis, and harass and retaliate against those who collect data or speak out about it, while also doing far too little to alleviate it." The report discusses a teaching physician who said "residents are threatened with being expelled from the program or their hospital if they include a malnutrition diagnosis in medical records", causing malnutrition to be understated in Venezuelan data. The report states that "many analysts have argued that the government's own policies have played a role in causing the economic crisis ... However, under the presidency of Nicolás Maduro, the Venezuelan government has denied the crisis, hidden health statistics and data, harassed health professionals who speak out about the reality on the ground, and made it harder for sufficient humanitarian assistance to reach the Venezuelan people. Through these policies and practices, authorities have contributed to the worsening humanitarian crisis documented in this report." The International Covenant on Economic, Social and Cultural Rights (ICESCR) is a multilateral treaty ratified by Venezuela; it commits its parties to "the enjoyment of the highest attainable standard of physical and mental health", and the right to an adequate "standard of living" and "adequate food". The Constitution of Venezuela provides for the right to health . [lower-alpha 6] The HRW/Johns Hopkins report states that, facing deteriorating health conditions, the government's suppression of information and actions against those speaking about the crisis "represent a violation of Venezuela's obligations to respect, protect, and fulfill the right to health" to which Venezuelans are entitled from both the ICESCR treaty and their Constitution. Following the April HRW/Johns Hopkins report, and amid announcements from the United Nations about the scale of the humanitarian crisis, along with increasing international pressure, Maduro met with the Red Cross, and it announced it would triple its budget for aid to Venezuela. The increased aid would focus in four areas: the migration crisis, the health care system collapse, water and sanitation, and prisons and detention centers. Maduro, for the first time, indicated he was prepared to accept international aid—although denying a humanitarian crisis exists. The Wall Street Journal said that the acceptance of humanitarian shipments by Maduro was his first acknowledgement that Venezuela is "suffering from an economic collapse", and The Guardian reported that Maduro's stance has softened in the face of increasing pressure. Guaidó said the acceptance of humanitarian aid was the "result of our pressure and insistence", and called on Venezuelans to "stay vigilant to make sure incoming aid is not diverted for 'corrupt' purposes". In 1961, Venezuela was the first country declared free of malaria . In 2009, the WHO reported there were less than 36,000 cases of malaria in Venezuela. In 2013, Venezuela registered a new high in the number of cases of malaria in the past 50 years, and by 2014, was the only country in Latin America where the incidence of malaria was increasing, allegedly in part due to illegal mining; [lower-alpha 7] medical shortages in the country hampered treatment. By 2016, Venezuela's malaria-prevention program had collapsed, and there were more than a hundred thousand cases of malaria yearly. In 2017, there were 414,000 confirmed cases of malaria, according to the WHO. Other preventable diseases that "were rare or nonexistent before the economic crisis, have surged", including diphtheria , measles , and tuberculosis . "Venezuela did not experience a single case of diphtheria between 2006 and 2015"; according to the HRW/Johns Hopkins report, since mid-2016, 1,500 of the 2,500 suspected cases have been confirmed. Between 2008 and 2015, there was one recorded case of measles, in 2012; since June 2017, 6,200 of the 9,300 reported cases have been confirmed. The highest rate of tuberculosis in four decades was reached in 2017. In 2014, there were 6,000 reported cases of tuberculosis; preliminary data shows more than 13,000 for 2017. In 2014, shortages of antiretroviral medicines to treat HIV/AIDS affected about 50,000 Venezuelans, potentially causing thousands of Venezuelans with HIV to develop AIDS. In 2018, PAHO estimated that 90% of Venezuelans who had HIV and were registered by the government—69,308 of the 79,467 registered —were not receiving antiretroviral treatment. The PAHO report estimated that in six years, new HIV cases grew by 24% through 2016, after which the government stopped providing data. NPR reported: "New HIV infections and AIDS-related deaths have increased sharply, in large part because the vast majority of HIV-positive Venezuelans no longer have access to antiretroviral medications." Because of a shortage of HIV test kits, there may be more people who have HIV but are not aware. The HRW/Johns Hopkins report says: "Venezuela is the only country in the world where large numbers of individuals living with HIV have been forced to discontinue their treatment as a result of the lack of availability of antiretroviral (ARV) medicines." In late 2014, Venezuelans began saying that due to shortages of medicines, it was hard to find acetaminophen to help alleviate symptoms of the newly introduced chikungunya virus, a potentially lethal mosquito-borne disease. In September 2014, the Venezuelan government stated that 400 Venezuelans were infected with chikungunya; the Central University of Venezuela stated that there could be between 65,000 and 117,000 Venezuelans infected. In August 2015 independent health monitors said that there were more than two million people infected with chikungunya while the government said there were 36,000 cases. As a result of the COVID-19 pandemic, which reached Venezuela in March 2020, costs for services such as internet and telephone lines rose between 80% and 749%, further limiting access to these utilities. Shortages of beds and essential medical equipment, such as latex gloves and antibiotics, have severely limited the capabilities of the country's medical infrastructure. In April 2020 the Venezuelan government asked the Bank of England to sell $US1.02 billion of the Venezuelan gold reserves held by the bank to help the government fund its response to the COVID-19 pandemic. This was followed on 14 May by a legal claim by the Venezuelan Central Bank (BCV) asking the Bank of England to send the proceeds of the sale of gold to the United Nations Development Programme . The claim stated that the funds would then be used to buy healthcare equipment, medicine, and food to address the country's "COVID-19 emergency". The UK Foreign Office had previously agreed to a request from the Trump administration to block the release of Venezuela's gold. In July 2020, the UK High Court ruled that the gold could not be released to the BCV because the UK government recognised Juan Guaidó as the "constitutional interim president of Venezuela". However, in October 2020, an appeals court overturned the High Court decision and asked the UK Foreign Office to clarify who it recognised as president of Venezuela. The Guardian wrote that the position of the UK government was unclear as it "maintains full consular and diplomatic relations with the Venezuela government". [ needs update ] In 2016, infant mortality increased 30% in one year, to 11,466 deaths of children under the age of one. By 2019, the UN reported that infant mortality had "soared". "Venezuela is the only South American country where infant mortality has returned to levels last seen in the 1990s", according to the HRW/Johns Hopkins report. Maternal mortality also increased 65% in one year, to 756 deaths. Abortion is illegal in Venezuela; the director of a large family planning clinic in Venezuela indicated that more women are arranging for permanent sterilization, and that more are presenting with "complications from clandestine abortions". One of the causes, according to the Venezuelan Association for Alternative Sexual Education, is the severe shortage of oral and injectable contraceptives and intrauterine devices . The HRW/Johns Hopkins report states that the more than 454,000 Venezuelan women who have emigrated to Colombia face 'threats of sexual exploitation and abuse, trafficking, and sexual and reproductive rights violations"; violence based on gender accounted for more than 12% of 2018 health-care events, and indigenous women may be at higher risk. Venezuelan women emigrating are at risk for becoming sex trafficking targets virtually anywhere they flee to. Cases of trafficking in Peru, the United States, Spain, and Colombia display the highest numbers. Due to lack of medical supplies, food and medical care in Venezuelan hospitals, many pregnant women in Venezuela are crossing the border into neighboring countries to give birth. Lack of basic medicine and equipment is causing preventable deaths and maternity is a very high risk for women, especially since there are no blood banks in the event of excessive bleeding. Hospitals frequently have water and electricity outages and only 7% of emergency services are fully operative. Maternal mortality is estimated to have increased by 65% from 2013 to 2016, and unsafe abortions have contributed to 20% of preventable maternal deaths. According to Amnesty International, causes of the increase in maternal deaths include a lack of medical personnel and supplies like anticoagulants, scar healing cream, painkillers, antibiotics, antiseptics, and other tools and equipment. Cúcuta, a city on the Colombian-Venezuela border, has received 14,000 Venezuelan patients at the Erasmo Meoz University Hospital since 2016 and is expecting to receive even more. In this hospital, 75% of the newborns born in the first two months of the year 2019 were Venezuelans. The situation has strained the budget of these hospitals, putting Erasmo Meoz 14 million dollars into debt. While Colombia is the most impacted since it shares a border, women are also traveling to Brazil to give birth. The number of births of Venezuelan babies attended to in Boa Vista, Brazil , has increased from 700 in 2014 to 50,000 in 2017. Venezuelan mothers have also been fleeing to neighboring Peru and Ecuador. For Colombian citizenship it is required that Colombian citizens be born to at least one Colombian parent or be born to foreign parents who meet residence requirements and are eligible to become citizens. Due to the influx of Venezuelan babies being born in Colombia and the Venezuelan government's inability to issue citizenship, Colombia has introduced a new measure that will give these Colombian-born newborns Colombian citizenship to avoid 'statelessness'. The measure went into effect August 2019 and includes babies of Venezuelan parents born in Colombia starting in January 2015, having given citizenship to approximately 27,000 babies born in Colombia over the past four years. Following the Bolivarian Revolution, the rate of suicide among Venezuelans quadrupled over two decades, with hundreds of thousands of Venezuelans dying from suicide during the period according to the Venezuelan Observatory of Violence. As a result of the crisis, stressors resulting in suicide included economic burden, hunger and loneliness due to the emigration of relatives. In 2015, concerns about shortages and inflation overtook violent crime as Venezuelans' main worry for the first time in years according to pollster Datanálisis. The chief executive of Datanálisis, Luis Vicente Leon, said that Venezuelans had greater concerns over shortages and became preoccupied with the difficulties surrounding them instead. Eldar Shafir , author and American behavioral scientist, said that the psychological "obsession" with finding scarce goods in Venezuela is because the rarity of the item makes it "precious". In 2016, reporters from The New York Times visited six psychiatric wards across the Venezuela at the invitation of doctors; all reported shortages of medicine and even food. In the investigation, they reported that El Pampero Hospital had not employed a psychiatrist in two years, and that it only had running water for only a few hours a day. The hospital, the article said, also suffered from shortages of basic personal-care and cleaning supplies, such as soap, shampoo, toothpaste or toilet paper. The nurses declared that without sedatives, they had to restrain patients or lock them in isolation cells to keep them from harming themselves. The reporters also noted that the government had denied that its public hospitals were suffering from shortages, and had refused multiple offers of international medical aid. Despite the threat of violent protests, the economic crisis affected children more than violence. Abel Saraiba, a psychologist with children's rights organization Cecodap said in 2017, "We have children from a very early age who are having to think about how to survive", with half of her young clients requiring treatment because of the crisis. Children are often forced to stand in food lines or beg with their parents, while the games they play with other children revolve around finding food. Friends of the Child Foundation psychologist Ninoska Zambrano said that children are offering sexual services for food. Zambrano said "Families are doing things that not only lead them to break physically, but in general, socially, we are being morally broken". In 2017, suicide increased by 67% among the elderly and 18% among minors; by 2018, reports emerged of a rapidly increasing suicide rate due to the stressors surrounding the crisis. Mission Barrio Adentro was a program established by Chávez to bring medical care to poor neighborhoods; it was staffed by Cubans that were sent to Venezuela in exchange for petroleum. The New York Times interviewed sixteen Cuban medical professionals in 2019 who had worked for Barrio Adentro prior to the 2018 Venezuelan presidential elections; all sixteen revealed that they were required to participate in voting fraud. Some of the Cubans said that "command centers" for elections were placed near clinics to facilitate "dispatching doctors to pressure residents". Some tactics reported by the Cubans were unrelated to their profession: they were given counterfeit cards to vote even though they were not eligible voters, they witnessed vote tampering when officials opening ballot boxes and destroyed ballots, and they were told to instruct easily manipulated elderly patients in how to vote. But they also "described a system of deliberate political manipulation"; their services as medical professionals "were wielded to secure votes for the governing Socialist Party, often through coercion", they told The New York Times . Facing a shortage of supplies and medicine, they were instructed to withhold treatment–even for emergencies–so supplies and treatment could be "doled out closer to the election, part of a national strategy to compel patients to vote for the government". They reported that life-saving treatment was denied to patients who supported the opposition. As the election neared, they were sent door-to-door, on house visits with a political purpose: "to hand out medicine and enlist voters for Venezuela's Socialist Party". Patients were warned that they could lose their medical care if they did not vote for the socialist party, and that, if Maduro lost, ties would be broken with Cuba, and Venezuelans would lose all medical care. Patients with chronic conditions, at risk of death if they couldn't get medicine, were a particular focus of these tactics. One said that government officials were posing as doctors to make these house calls before elections; 'We, the doctors, were asked to give our extra robes to people. The fake doctors were even giving out medicines, without knowing what they were or how to use them," he said. Since the mid-2000s during Chávez's presidency, Venezuela has had a housing crisis. In 2005, the Venezuelan Construction Chamber (CVC) estimated that there was a shortage of 1.6 million homes, with only 10,000 of 120,000 promised homes constructed by Chávez's government despite billions of dollars in investments. Poor Venezuelans attempted to construct homes on their own despite structural risks. By 2011, there was a housing shortage of 2 million homes, with nearly twenty prime developments being occupied by squatters following Chávez's call for the poor to occupy "unused land". Up to 2011, only 500,000 homes were constructed during the Chávez administration, with over two-thirds of the new housing developments being built by private companies; his government provided about the same amount of housing as previous administrations. Housing shortages were further exacerbated when private construction halted due to the fear of property expropriations and because of the government's inability to construct and provide housing. Urban theorist and author Mike Davis said in July 2011 to The Guardian , "Despite official rhetoric, the Bolivarianist regime has undertaken no serious redistribution of wealth in the cities and oil revenues pay for too many other programmes and subsidies to leave room for new housing construction." By 2012, a shortage of building materials also disrupted construction, with metal production at a 16-year low. By the end of Chávez's presidency in 2013, the number of Venezuelans in inadequate housing had grown to 3 million. Under the Maduro government, housing shortages continued to worsen. Maduro announced in 2014 that due to the shortage of steel, abandoned cars and other vehicles would be acquired by the government and melted to provide rebar for housing. In April 2014, Maduro ruled by decree that Venezuelans who owned three or more rental properties would be forced by the government to sell their rental units at a set price or they would face fines or have their property possessed by the government. By 2016, residents of government-provided housing, who were usually supporters of the government, began protesting due to the lack of utilities and food. The Wall Street Journal reported in March 2019 that poverty was double that of 2014. A study from Andrés Bello Catholic University indicated that by 2019 at least 8 million Venezuelans did not have enough to eat. A UN report estimated in March 2019 that 94% of Venezuelans live in poverty, and that one quarter of Venezuelans need some form of humanitarian assistance . According to the Living Conditions Survey by the Andrés Bello Catholic University (Encovi in Spanish, Encuesta de Condiciones de Vida ), by 2021 94.5% of the population was in poverty based on income, out of which 76.6% lived under extreme poverty, the highest figure ever recorded in the country. More than 70% of Venezuela's food is imported; Venezuela became so dependent on food imports that it could no longer afford when the price of oil dropped in 2014. Chávez gave the military control of food, and nationalized much of the industry, which was then neglected, leading to production shortages. With a "diminished food supply", Maduro put "generals in charge of everything from butter to rice". With the military in charge of food, food trafficking became profitable, bribes and corruption common, and food did not reach the needy. The government imports most of the food the country needs, it is controlled by the military, and the price paid for food is higher than justified by market prices. Venezuelans were spending "all day waiting in lines" to buy rationed food, "pediatric wards filled up with underweight children, and formerly middle-class adults began picking through rubbish bins for scraps". Several other factors have led to shortages: imports over the two years until the end of 2017 declined by two-thirds; hyperinflation has made food too costly for many Venezuelans; and for those who depend on food boxes supplied by the government, "these do not reach all Venezuelans who need them, provision of boxes is intermittent, and receipt is often linked to political support of the government". Corruption became a problem in the distribution of food. The operations director at one food import business says "he pays off a long roster of military officials for each shipment of food he brings in from ... the US. It's an unbroken chain of bribery from when your ship comes in until the food is driven out in trucks." A National Guard lieutenant denies this charge, saying corruption would be worse if the military were not involved; government and military officials say the opposition is overstating the corruption problem for their own benefit. Retired General Antonio Rivero said that "Maduro is trying to prevent soldiers from going hungry and being tempted to participate in an uprising against an increasingly unpopular government", adding that using the military to control food distribution has "drained the feeling of rebellion from the armed forces" by giving soldiers access to food denied others, with the resulting corruption increasing shortages for the general public. The colectivos are also involved in food trafficking, selling food on the black market; a colectivo leader told InSight Crime that trafficking food and medicine is as profitable as drug-running, but carries less risk. With shadowy connections to the government, The Washington Post says "some have been put in charge of the distribution of government food packages in poor areas—giving them control over hungry neighborhoods." The Associated Press reports that people gather every evening in downtown Caracas in search of food thrown out on a sidewalk; the people are typically unemployed, but are "frequently joined by small business owners, college students and pensioners—people who consider themselves middle class even though their living standards have long ago been pulverized by triple-digit inflation, food shortages and a collapsing currency". A waste collection official in Maracaibo reported that most of the trash bags he received had been gone through by people searching for food. One dump reports finding parts of dismembered animals, like "dogs, cats, donkeys, horses and pigeons" and there is evidence that people are eating wildlife such as anteaters, flamingos, vultures and lizards. "Hunger, malnutrition, and severe food shortages are widespread in all Venezuela", according to Human Rights Watch. Doctors at 21 public hospitals in 17 Venezuelan states told The New York Times in 2017 that "their emergency rooms were being overwhelmed by children with severe malnutrition—a condition they had rarely encountered before the economic crisis began", and that "hundreds have died". The government has responded with "a near-total blackout of health statistics, and by creating a culture in which doctors are often afraid to register cases and deaths that may be associated with the government's failures". The Food and Agriculture Organization of the UN said that less than 5% of Venezuelans were undernourished between 2008 and 2013, but that number had more than doubled, to almost 12% from 2015 and 2017, representing 3.7 million people. A 2016 survey found that almost three-quarters of the population said that, because of improper nutrition, they had lost on average 8.7 kg (19.4 lbs) and 64% said they lost 11 kg (24 lbs) in 2017. A 2016 Venebarometro poll of 1,200 Venezuelans found almost half are no longer able to eat three daily meals; the government blames this on an "economic war" they say is waged by the opposition. A UN report said that because of lack of water and sanitation, 4.3 million Venezuelans needed assistance in 2019. During the 2019 Venezuelan blackouts which started on 7 March, the water distribution system also had shortages. José de Viana, an engineer and former president of Hidrocapital, the municipal water company in Caracas , said that 90% of the thermoelectric plants that work as a backup if power fails are not operational because of lack of maintenance, or they have been simply disconnected, and that "the most important population centers in the country [had] zero water supply for more than four days". Analysts said that two-thirds of Venezuela's population (20 million people) were without water, partially or completely, in the weeks after the blackouts. People swarmed the polluted Guaire River in the center of Caracas to fill plastic containers with contaminated water, or collected water from streams at El Ávila National Park . Others tried to catch water from the city's sewer drains. In the state of Lara people bathed in the sewers. The head of the infectious disease department at the University Hospital of Caracas , María Eugenia Landaeta said that, without access to clean water, the chance of people contracting bacterial infections increased, and that doctors had seen during the blackouts "surges in diarrhea, typhoid fever and hepatitis A ", while non-sterile water and lack of hygiene was contributing to postpartum infections . The University Hospital goes months without dependable water or power supply, and depends on water tanks and power generators. The crisis has affected the life of the average Venezuelan on all levels. By 2017, hunger had escalated to the point where almost seventy-five percent of the population had lost an average of over 8 kg (over 19 lbs) in weight [lower-alpha 5] and more than half did not have enough income to meet their basic food needs. An UN report estimated in March 2019 that 94% of Venezuelans lived in poverty, and by 2021 almost twenty percent of Venezuelans (5.4 million) had left their country. The UN analysis estimates in 2019 that 25% of Venezuelans need some form of humanitarian assistance. Venezuela led the world in murder rates , with 81.4 per 100,000 people killed in 2018, making it the third most violent country in the world. Following increased international sanctions throughout 2019, the Maduro government abandoned policies established by Chávez such as price and currency controls, which resulted in the country seeing a temporary rebound from economic decline before COVID-19 entered Venezuela the following year. As a response to the devaluation of the official bolívar currency , by 2019 the population increasingly started relying on US dollars for transactions. Maduro described dollarization as an "escape valve" that helps the recovery of the country, the spread of productive forces in the country and the economy. However, Maduro said that the Venezuelan bolívar remained as the national currency. During the Bolivarian Revolution, the government began providing free healthcare, with Cuban medical professionals providing aid. The government's failure to concentrate on healthcare and a reduction in spending on healthcare, along with unchecked government corruption resulted in avoidable deaths due to severe shortages of medical supplies and equipment, and the emigration of medical professionals to other countries. Venezuela's reliance on imported goods and the complicated exchange rates initiated under Chávez led to increasing shortages during the late 2000s and into the 2010s that affected the availability of medicines and medical equipment in the country. Associated Press says the government stopped publishing medical statistics in 2010. The Health Minister changed multiple times during Chávez's presidency. According to a high-ranking official of Venezuela's Health Ministry, the ministers were treated as scapegoats whenever issues with public health arose in Venezuela. He also said that officials of the Health Ministry engaged in corruption to enrich themselves by selling goods intended for public healthcare to others. Early in the Maduro presidency, the government could not supply enough money for medical supplies among healthcare providers, with the president of the Venezuelan Medical Federation saying that 9 of 10 large hospitals had only 7% of required supplies and private doctors reporting numbers of patients that are "impossible" to count "dying from easily treatable illnesses when Venezuela's downward economic slide accelerated after Chávez's death". Many Venezuelans died avoidable deaths with medical professionals having scarce resources and using methods that were replaced decades ago. In February 2014, doctors at the University of Caracas Medical Hospital stopped performing surgeries due to the lack of supplies, even though nearly 3,000 people required surgery. By early 2015, only 35% of hospital beds were available and 50% of operating rooms could not function due to the lack of resources. In March 2015, a Venezuelan NGO, Red de Medicos por la Salud, reported that there was a 68% shortage of surgical supplies and a 70% shortage of medicines in Venezuelan pharmacies. In 2018, the Pan American Health Organization (PAHO) reported that approximately one-third (22,000 of 66,138) of registered physicians left Venezuela as of 2014. Rosemary DiCarlo from the UN said that 40% of medical professionals had left Venezuela and supplies of medicine were at 20% of levels needed. The Venezuelan Medical Federation said that doctors were leaving the public health care system because of shortages of drugs and equipment and poor pay. In August 2015 Human Rights Watch said "We have rarely seen access to essential medicines deteriorate as quickly as it has in Venezuela except in war zones." In 2015, the government reported that a third of patients admitted to public hospitals died. The medications of individuals who die are re-distributed through small-scale and local efforts, with the help of the families of the deceased, to try to supply surviving patients. One study of 6,500 households by three of the main universities in Venezuela found that "74% of the population had lost on average nineteen pounds in 2016". In April 2017 Venezuela's health ministry reported that maternal mortality jumped by 65% in 2016 and that the number of infant deaths rose by 30%. It also said that the number of cases of malaria was up by 76%. Shortly after Minister of Health Antonieta Caporale released in 2017 this data, and health statistics showing increases in 2016 infant and maternal mortality and infectious diseases, Maduro fired her and replaced the physician with a pharmacist close to vice-president Tareck El Aissami , Luis López Chejade. The publications were removed from the Ministry's website, and no further health data has been made available, although the government had produced health bulletins for several decades. In March 2019, The Wall Street Journal reported that the "collapse of Venezuela's health system, once one of the best in Latin America, has led to a surge in infant and maternal mortality rates and a return of rare diseases that were considered all but eradicated. Health officials say malaria, yellow fever, diphtheria, dengue and tuberculosis are now spreading from Venezuela to neighboring countries as Venezuelan refugees surge over borders." The United Nations estimated in 2019 that 2.8 million Venezuelans have healthcare needs, 300,000 are at risk of dying with cancer, diabetes or HIV as they have not had access to medicine for more than a year, and preventable diseases like diphtheria, malaria, measles and tuberculosis are rising in 2019, along with hepatitis A, because of sanitation and lack of access to water. The April 2019 HRW/Johns Hopkins report showed this rise in infectious and preventable diseases, as well as increasing malnutrition, infant and maternal death, and undertreatment of HIV . Inflation and medicine shortages have meant that patients are asked to bring their own food, water and soap, and medical supplies including scalpels and syringes. In August 2019, as part of regional efforts to help Venezuelan migrants, the United States promised that it will provide thousands of doses of HIV medication to prevent the spread of HIV/AIDS and to treat those who have it. In April 2019, Human Rights Watch (HRW) and Johns Hopkins Bloomberg School of Public Health published the results of a joint, year-long research project in a report entitled "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". Combined with data from the World Health Organization (WHO), the PAHO and Venezuelan sources, the report was based on 156 interviews with Venezuelan emigrants to Colombia and Brazil, officials from relief and humanitarian organizations, Venezuelan health care professionals, and UN and government officials from Brazil and Colombia. Most of the interviews occurred in July or August 2018 in visits by the experts to the Venezuelan border towns of Cúcuta , Colombia and Boa Vista or Pacaraima , Brazil. The Washington Post stated that the HRW/Johns Hopkins report "paints an extremely grim picture of life in Venezuela, whose once-prosperous economy has imploded because of mismanagement and corruption under Maduro"; it documents rising maternal and infant death, spread of preventable diseases, food insecurity, and child malnutrition. HRW declared that the "combination of severe medicine and food shortages ... with the spread of disease ... amounts to a complex humanitarian emergency that requires a full-scale response by the United Nations secretary-general." The Washington Post states that the report describes a healthcare system that is in "utter collapse", with diseases that are preventable via vaccination spreading, and "dramatic surges" in infectious diseases once eradicated in Venezuela. The economic crisis in Venezuela started around 2010, and the health crisis followed by two years and significantly worsened in 2017, but the situation in 2019 "is even more dismal than researchers expected". Paul Spiegel, MD, who was the editor and reviewer of the report said, "Venezuela is a middle-income country with a previously strong infrastructure, so just to see this incredible decline ... in such a short period of time is quite astonishing." Alberto Paniz-Mondolfi , a doctor in Barquisimeto , Venezuela who is a member of the Venezuelan National Academy of Medicine, told NPR that the report gave an accurate, thorough and timely depiction of the medical situation in his country; he had no affiliation with the report, but said that he had seen cases where there were not even catheters for hooking up children who appeared to have malnutrition for intravenous therapy . Spiegel adds that, because of the infrastructure and trained personnel in Venezuela, aid can be distributed quickly once delivered to Venezuela. On May 16, 2018, President Maduro said that "everything [that has been said] about measles and diphtheria is a lie, we vaccinate the whole community for free" and that "with regards to food, Venezuela has unique policies, which have enabled us to carry on with a program allowing us to maintain levels of food that are necessary for the people." Days later, the undersecretary of health, Indhriana Parada, gave a speech at WHO highlighting the "achievements" of the Venezuelan health system. She said that "in Venezuela there is no humanitarian crisis" and that "Venezuela guarantees access to basic medicines to the most vulnerable groups through distribution policies." In the case of malaria, she said that government measures had "reduced incidence by 50 percent". "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". The Maduro administration does not publish health statistics, but rather it "paint[s] a rosy picture of its health care system". The Guardian reported Maduro's response to the country's health care crisis as "inadequate". "Because of the intransigence of President Nicolás Maduro—who has blamed deprivations on US sanctions and refused to allow anything beyond a trickle of assistance to enter the country"—aid has not been delivered quickly enough. Reuters reported that "Maduro says there is no crisis and no need for humanitarian aid, blaming U.S. sanctions for the country's economic problems." Venezuela's Foreign Minister Jorge Arreaza did not respond to a letter asking for Venezuela's "views regarding the extent of the crisis and the policies it was implementing to address it" before the HRW/Johns Hopkins report was published. The HRW summary of the HRW/Johns Hopkins report said, "The Venezuelan authorities during the presidency of Nicolás Maduro have proven unable to stem the crisis, and have in fact exacerbated it through their efforts to suppress information about the scale and urgency of the problems." The Associated Press said Maduro "suppress[es] information" and has made the problem worse. The Americas director for HRW, José Miguel Vivanco said, "Venezuelan authorities publicly minimise and suppress information about the crisis, and harass and retaliate against those who collect data or speak out about it, while also doing far too little to alleviate it." The report discusses a teaching physician who said "residents are threatened with being expelled from the program or their hospital if they include a malnutrition diagnosis in medical records", causing malnutrition to be understated in Venezuelan data. The report states that "many analysts have argued that the government's own policies have played a role in causing the economic crisis ... However, under the presidency of Nicolás Maduro, the Venezuelan government has denied the crisis, hidden health statistics and data, harassed health professionals who speak out about the reality on the ground, and made it harder for sufficient humanitarian assistance to reach the Venezuelan people. Through these policies and practices, authorities have contributed to the worsening humanitarian crisis documented in this report." The International Covenant on Economic, Social and Cultural Rights (ICESCR) is a multilateral treaty ratified by Venezuela; it commits its parties to "the enjoyment of the highest attainable standard of physical and mental health", and the right to an adequate "standard of living" and "adequate food". The Constitution of Venezuela provides for the right to health . [lower-alpha 6] The HRW/Johns Hopkins report states that, facing deteriorating health conditions, the government's suppression of information and actions against those speaking about the crisis "represent a violation of Venezuela's obligations to respect, protect, and fulfill the right to health" to which Venezuelans are entitled from both the ICESCR treaty and their Constitution. Following the April HRW/Johns Hopkins report, and amid announcements from the United Nations about the scale of the humanitarian crisis, along with increasing international pressure, Maduro met with the Red Cross, and it announced it would triple its budget for aid to Venezuela. The increased aid would focus in four areas: the migration crisis, the health care system collapse, water and sanitation, and prisons and detention centers. Maduro, for the first time, indicated he was prepared to accept international aid—although denying a humanitarian crisis exists. The Wall Street Journal said that the acceptance of humanitarian shipments by Maduro was his first acknowledgement that Venezuela is "suffering from an economic collapse", and The Guardian reported that Maduro's stance has softened in the face of increasing pressure. Guaidó said the acceptance of humanitarian aid was the "result of our pressure and insistence", and called on Venezuelans to "stay vigilant to make sure incoming aid is not diverted for 'corrupt' purposes". In 1961, Venezuela was the first country declared free of malaria . In 2009, the WHO reported there were less than 36,000 cases of malaria in Venezuela. In 2013, Venezuela registered a new high in the number of cases of malaria in the past 50 years, and by 2014, was the only country in Latin America where the incidence of malaria was increasing, allegedly in part due to illegal mining; [lower-alpha 7] medical shortages in the country hampered treatment. By 2016, Venezuela's malaria-prevention program had collapsed, and there were more than a hundred thousand cases of malaria yearly. In 2017, there were 414,000 confirmed cases of malaria, according to the WHO. Other preventable diseases that "were rare or nonexistent before the economic crisis, have surged", including diphtheria , measles , and tuberculosis . "Venezuela did not experience a single case of diphtheria between 2006 and 2015"; according to the HRW/Johns Hopkins report, since mid-2016, 1,500 of the 2,500 suspected cases have been confirmed. Between 2008 and 2015, there was one recorded case of measles, in 2012; since June 2017, 6,200 of the 9,300 reported cases have been confirmed. The highest rate of tuberculosis in four decades was reached in 2017. In 2014, there were 6,000 reported cases of tuberculosis; preliminary data shows more than 13,000 for 2017. In 2014, shortages of antiretroviral medicines to treat HIV/AIDS affected about 50,000 Venezuelans, potentially causing thousands of Venezuelans with HIV to develop AIDS. In 2018, PAHO estimated that 90% of Venezuelans who had HIV and were registered by the government—69,308 of the 79,467 registered —were not receiving antiretroviral treatment. The PAHO report estimated that in six years, new HIV cases grew by 24% through 2016, after which the government stopped providing data. NPR reported: "New HIV infections and AIDS-related deaths have increased sharply, in large part because the vast majority of HIV-positive Venezuelans no longer have access to antiretroviral medications." Because of a shortage of HIV test kits, there may be more people who have HIV but are not aware. The HRW/Johns Hopkins report says: "Venezuela is the only country in the world where large numbers of individuals living with HIV have been forced to discontinue their treatment as a result of the lack of availability of antiretroviral (ARV) medicines." In late 2014, Venezuelans began saying that due to shortages of medicines, it was hard to find acetaminophen to help alleviate symptoms of the newly introduced chikungunya virus, a potentially lethal mosquito-borne disease. In September 2014, the Venezuelan government stated that 400 Venezuelans were infected with chikungunya; the Central University of Venezuela stated that there could be between 65,000 and 117,000 Venezuelans infected. In August 2015 independent health monitors said that there were more than two million people infected with chikungunya while the government said there were 36,000 cases. As a result of the COVID-19 pandemic, which reached Venezuela in March 2020, costs for services such as internet and telephone lines rose between 80% and 749%, further limiting access to these utilities. Shortages of beds and essential medical equipment, such as latex gloves and antibiotics, have severely limited the capabilities of the country's medical infrastructure. In April 2020 the Venezuelan government asked the Bank of England to sell $US1.02 billion of the Venezuelan gold reserves held by the bank to help the government fund its response to the COVID-19 pandemic. This was followed on 14 May by a legal claim by the Venezuelan Central Bank (BCV) asking the Bank of England to send the proceeds of the sale of gold to the United Nations Development Programme . The claim stated that the funds would then be used to buy healthcare equipment, medicine, and food to address the country's "COVID-19 emergency". The UK Foreign Office had previously agreed to a request from the Trump administration to block the release of Venezuela's gold. In July 2020, the UK High Court ruled that the gold could not be released to the BCV because the UK government recognised Juan Guaidó as the "constitutional interim president of Venezuela". However, in October 2020, an appeals court overturned the High Court decision and asked the UK Foreign Office to clarify who it recognised as president of Venezuela. The Guardian wrote that the position of the UK government was unclear as it "maintains full consular and diplomatic relations with the Venezuela government". [ needs update ] In 2016, infant mortality increased 30% in one year, to 11,466 deaths of children under the age of one. By 2019, the UN reported that infant mortality had "soared". "Venezuela is the only South American country where infant mortality has returned to levels last seen in the 1990s", according to the HRW/Johns Hopkins report. Maternal mortality also increased 65% in one year, to 756 deaths. Abortion is illegal in Venezuela; the director of a large family planning clinic in Venezuela indicated that more women are arranging for permanent sterilization, and that more are presenting with "complications from clandestine abortions". One of the causes, according to the Venezuelan Association for Alternative Sexual Education, is the severe shortage of oral and injectable contraceptives and intrauterine devices . The HRW/Johns Hopkins report states that the more than 454,000 Venezuelan women who have emigrated to Colombia face 'threats of sexual exploitation and abuse, trafficking, and sexual and reproductive rights violations"; violence based on gender accounted for more than 12% of 2018 health-care events, and indigenous women may be at higher risk. Venezuelan women emigrating are at risk for becoming sex trafficking targets virtually anywhere they flee to. Cases of trafficking in Peru, the United States, Spain, and Colombia display the highest numbers. Due to lack of medical supplies, food and medical care in Venezuelan hospitals, many pregnant women in Venezuela are crossing the border into neighboring countries to give birth. Lack of basic medicine and equipment is causing preventable deaths and maternity is a very high risk for women, especially since there are no blood banks in the event of excessive bleeding. Hospitals frequently have water and electricity outages and only 7% of emergency services are fully operative. Maternal mortality is estimated to have increased by 65% from 2013 to 2016, and unsafe abortions have contributed to 20% of preventable maternal deaths. According to Amnesty International, causes of the increase in maternal deaths include a lack of medical personnel and supplies like anticoagulants, scar healing cream, painkillers, antibiotics, antiseptics, and other tools and equipment. Cúcuta, a city on the Colombian-Venezuela border, has received 14,000 Venezuelan patients at the Erasmo Meoz University Hospital since 2016 and is expecting to receive even more. In this hospital, 75% of the newborns born in the first two months of the year 2019 were Venezuelans. The situation has strained the budget of these hospitals, putting Erasmo Meoz 14 million dollars into debt. While Colombia is the most impacted since it shares a border, women are also traveling to Brazil to give birth. The number of births of Venezuelan babies attended to in Boa Vista, Brazil , has increased from 700 in 2014 to 50,000 in 2017. Venezuelan mothers have also been fleeing to neighboring Peru and Ecuador. For Colombian citizenship it is required that Colombian citizens be born to at least one Colombian parent or be born to foreign parents who meet residence requirements and are eligible to become citizens. Due to the influx of Venezuelan babies being born in Colombia and the Venezuelan government's inability to issue citizenship, Colombia has introduced a new measure that will give these Colombian-born newborns Colombian citizenship to avoid 'statelessness'. The measure went into effect August 2019 and includes babies of Venezuelan parents born in Colombia starting in January 2015, having given citizenship to approximately 27,000 babies born in Colombia over the past four years. Following the Bolivarian Revolution, the rate of suicide among Venezuelans quadrupled over two decades, with hundreds of thousands of Venezuelans dying from suicide during the period according to the Venezuelan Observatory of Violence. As a result of the crisis, stressors resulting in suicide included economic burden, hunger and loneliness due to the emigration of relatives. In 2015, concerns about shortages and inflation overtook violent crime as Venezuelans' main worry for the first time in years according to pollster Datanálisis. The chief executive of Datanálisis, Luis Vicente Leon, said that Venezuelans had greater concerns over shortages and became preoccupied with the difficulties surrounding them instead. Eldar Shafir , author and American behavioral scientist, said that the psychological "obsession" with finding scarce goods in Venezuela is because the rarity of the item makes it "precious". In 2016, reporters from The New York Times visited six psychiatric wards across the Venezuela at the invitation of doctors; all reported shortages of medicine and even food. In the investigation, they reported that El Pampero Hospital had not employed a psychiatrist in two years, and that it only had running water for only a few hours a day. The hospital, the article said, also suffered from shortages of basic personal-care and cleaning supplies, such as soap, shampoo, toothpaste or toilet paper. The nurses declared that without sedatives, they had to restrain patients or lock them in isolation cells to keep them from harming themselves. The reporters also noted that the government had denied that its public hospitals were suffering from shortages, and had refused multiple offers of international medical aid. Despite the threat of violent protests, the economic crisis affected children more than violence. Abel Saraiba, a psychologist with children's rights organization Cecodap said in 2017, "We have children from a very early age who are having to think about how to survive", with half of her young clients requiring treatment because of the crisis. Children are often forced to stand in food lines or beg with their parents, while the games they play with other children revolve around finding food. Friends of the Child Foundation psychologist Ninoska Zambrano said that children are offering sexual services for food. Zambrano said "Families are doing things that not only lead them to break physically, but in general, socially, we are being morally broken". In 2017, suicide increased by 67% among the elderly and 18% among minors; by 2018, reports emerged of a rapidly increasing suicide rate due to the stressors surrounding the crisis. Mission Barrio Adentro was a program established by Chávez to bring medical care to poor neighborhoods; it was staffed by Cubans that were sent to Venezuela in exchange for petroleum. The New York Times interviewed sixteen Cuban medical professionals in 2019 who had worked for Barrio Adentro prior to the 2018 Venezuelan presidential elections; all sixteen revealed that they were required to participate in voting fraud. Some of the Cubans said that "command centers" for elections were placed near clinics to facilitate "dispatching doctors to pressure residents". Some tactics reported by the Cubans were unrelated to their profession: they were given counterfeit cards to vote even though they were not eligible voters, they witnessed vote tampering when officials opening ballot boxes and destroyed ballots, and they were told to instruct easily manipulated elderly patients in how to vote. But they also "described a system of deliberate political manipulation"; their services as medical professionals "were wielded to secure votes for the governing Socialist Party, often through coercion", they told The New York Times . Facing a shortage of supplies and medicine, they were instructed to withhold treatment–even for emergencies–so supplies and treatment could be "doled out closer to the election, part of a national strategy to compel patients to vote for the government". They reported that life-saving treatment was denied to patients who supported the opposition. As the election neared, they were sent door-to-door, on house visits with a political purpose: "to hand out medicine and enlist voters for Venezuela's Socialist Party". Patients were warned that they could lose their medical care if they did not vote for the socialist party, and that, if Maduro lost, ties would be broken with Cuba, and Venezuelans would lose all medical care. Patients with chronic conditions, at risk of death if they couldn't get medicine, were a particular focus of these tactics. One said that government officials were posing as doctors to make these house calls before elections; 'We, the doctors, were asked to give our extra robes to people. The fake doctors were even giving out medicines, without knowing what they were or how to use them," he said. In April 2019, Human Rights Watch (HRW) and Johns Hopkins Bloomberg School of Public Health published the results of a joint, year-long research project in a report entitled "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". Combined with data from the World Health Organization (WHO), the PAHO and Venezuelan sources, the report was based on 156 interviews with Venezuelan emigrants to Colombia and Brazil, officials from relief and humanitarian organizations, Venezuelan health care professionals, and UN and government officials from Brazil and Colombia. Most of the interviews occurred in July or August 2018 in visits by the experts to the Venezuelan border towns of Cúcuta , Colombia and Boa Vista or Pacaraima , Brazil. The Washington Post stated that the HRW/Johns Hopkins report "paints an extremely grim picture of life in Venezuela, whose once-prosperous economy has imploded because of mismanagement and corruption under Maduro"; it documents rising maternal and infant death, spread of preventable diseases, food insecurity, and child malnutrition. HRW declared that the "combination of severe medicine and food shortages ... with the spread of disease ... amounts to a complex humanitarian emergency that requires a full-scale response by the United Nations secretary-general." The Washington Post states that the report describes a healthcare system that is in "utter collapse", with diseases that are preventable via vaccination spreading, and "dramatic surges" in infectious diseases once eradicated in Venezuela. The economic crisis in Venezuela started around 2010, and the health crisis followed by two years and significantly worsened in 2017, but the situation in 2019 "is even more dismal than researchers expected". Paul Spiegel, MD, who was the editor and reviewer of the report said, "Venezuela is a middle-income country with a previously strong infrastructure, so just to see this incredible decline ... in such a short period of time is quite astonishing." Alberto Paniz-Mondolfi , a doctor in Barquisimeto , Venezuela who is a member of the Venezuelan National Academy of Medicine, told NPR that the report gave an accurate, thorough and timely depiction of the medical situation in his country; he had no affiliation with the report, but said that he had seen cases where there were not even catheters for hooking up children who appeared to have malnutrition for intravenous therapy . Spiegel adds that, because of the infrastructure and trained personnel in Venezuela, aid can be distributed quickly once delivered to Venezuela. On May 16, 2018, President Maduro said that "everything [that has been said] about measles and diphtheria is a lie, we vaccinate the whole community for free" and that "with regards to food, Venezuela has unique policies, which have enabled us to carry on with a program allowing us to maintain levels of food that are necessary for the people." Days later, the undersecretary of health, Indhriana Parada, gave a speech at WHO highlighting the "achievements" of the Venezuelan health system. She said that "in Venezuela there is no humanitarian crisis" and that "Venezuela guarantees access to basic medicines to the most vulnerable groups through distribution policies." In the case of malaria, she said that government measures had "reduced incidence by 50 percent". "Venezuela's humanitarian emergency: Large-scale UN response needed to address health and food crises". The Maduro administration does not publish health statistics, but rather it "paint[s] a rosy picture of its health care system". The Guardian reported Maduro's response to the country's health care crisis as "inadequate". "Because of the intransigence of President Nicolás Maduro—who has blamed deprivations on US sanctions and refused to allow anything beyond a trickle of assistance to enter the country"—aid has not been delivered quickly enough. Reuters reported that "Maduro says there is no crisis and no need for humanitarian aid, blaming U.S. sanctions for the country's economic problems." Venezuela's Foreign Minister Jorge Arreaza did not respond to a letter asking for Venezuela's "views regarding the extent of the crisis and the policies it was implementing to address it" before the HRW/Johns Hopkins report was published. The HRW summary of the HRW/Johns Hopkins report said, "The Venezuelan authorities during the presidency of Nicolás Maduro have proven unable to stem the crisis, and have in fact exacerbated it through their efforts to suppress information about the scale and urgency of the problems." The Associated Press said Maduro "suppress[es] information" and has made the problem worse. The Americas director for HRW, José Miguel Vivanco said, "Venezuelan authorities publicly minimise and suppress information about the crisis, and harass and retaliate against those who collect data or speak out about it, while also doing far too little to alleviate it." The report discusses a teaching physician who said "residents are threatened with being expelled from the program or their hospital if they include a malnutrition diagnosis in medical records", causing malnutrition to be understated in Venezuelan data. The report states that "many analysts have argued that the government's own policies have played a role in causing the economic crisis ... However, under the presidency of Nicolás Maduro, the Venezuelan government has denied the crisis, hidden health statistics and data, harassed health professionals who speak out about the reality on the ground, and made it harder for sufficient humanitarian assistance to reach the Venezuelan people. Through these policies and practices, authorities have contributed to the worsening humanitarian crisis documented in this report." The International Covenant on Economic, Social and Cultural Rights (ICESCR) is a multilateral treaty ratified by Venezuela; it commits its parties to "the enjoyment of the highest attainable standard of physical and mental health", and the right to an adequate "standard of living" and "adequate food". The Constitution of Venezuela provides for the right to health . [lower-alpha 6] The HRW/Johns Hopkins report states that, facing deteriorating health conditions, the government's suppression of information and actions against those speaking about the crisis "represent a violation of Venezuela's obligations to respect, protect, and fulfill the right to health" to which Venezuelans are entitled from both the ICESCR treaty and their Constitution. Following the April HRW/Johns Hopkins report, and amid announcements from the United Nations about the scale of the humanitarian crisis, along with increasing international pressure, Maduro met with the Red Cross, and it announced it would triple its budget for aid to Venezuela. The increased aid would focus in four areas: the migration crisis, the health care system collapse, water and sanitation, and prisons and detention centers. Maduro, for the first time, indicated he was prepared to accept international aid—although denying a humanitarian crisis exists. The Wall Street Journal said that the acceptance of humanitarian shipments by Maduro was his first acknowledgement that Venezuela is "suffering from an economic collapse", and The Guardian reported that Maduro's stance has softened in the face of increasing pressure. Guaidó said the acceptance of humanitarian aid was the "result of our pressure and insistence", and called on Venezuelans to "stay vigilant to make sure incoming aid is not diverted for 'corrupt' purposes". In 1961, Venezuela was the first country declared free of malaria . In 2009, the WHO reported there were less than 36,000 cases of malaria in Venezuela. In 2013, Venezuela registered a new high in the number of cases of malaria in the past 50 years, and by 2014, was the only country in Latin America where the incidence of malaria was increasing, allegedly in part due to illegal mining; [lower-alpha 7] medical shortages in the country hampered treatment. By 2016, Venezuela's malaria-prevention program had collapsed, and there were more than a hundred thousand cases of malaria yearly. In 2017, there were 414,000 confirmed cases of malaria, according to the WHO. Other preventable diseases that "were rare or nonexistent before the economic crisis, have surged", including diphtheria , measles , and tuberculosis . "Venezuela did not experience a single case of diphtheria between 2006 and 2015"; according to the HRW/Johns Hopkins report, since mid-2016, 1,500 of the 2,500 suspected cases have been confirmed. Between 2008 and 2015, there was one recorded case of measles, in 2012; since June 2017, 6,200 of the 9,300 reported cases have been confirmed. The highest rate of tuberculosis in four decades was reached in 2017. In 2014, there were 6,000 reported cases of tuberculosis; preliminary data shows more than 13,000 for 2017. In 2014, shortages of antiretroviral medicines to treat HIV/AIDS affected about 50,000 Venezuelans, potentially causing thousands of Venezuelans with HIV to develop AIDS. In 2018, PAHO estimated that 90% of Venezuelans who had HIV and were registered by the government—69,308 of the 79,467 registered —were not receiving antiretroviral treatment. The PAHO report estimated that in six years, new HIV cases grew by 24% through 2016, after which the government stopped providing data. NPR reported: "New HIV infections and AIDS-related deaths have increased sharply, in large part because the vast majority of HIV-positive Venezuelans no longer have access to antiretroviral medications." Because of a shortage of HIV test kits, there may be more people who have HIV but are not aware. The HRW/Johns Hopkins report says: "Venezuela is the only country in the world where large numbers of individuals living with HIV have been forced to discontinue their treatment as a result of the lack of availability of antiretroviral (ARV) medicines." In late 2014, Venezuelans began saying that due to shortages of medicines, it was hard to find acetaminophen to help alleviate symptoms of the newly introduced chikungunya virus, a potentially lethal mosquito-borne disease. In September 2014, the Venezuelan government stated that 400 Venezuelans were infected with chikungunya; the Central University of Venezuela stated that there could be between 65,000 and 117,000 Venezuelans infected. In August 2015 independent health monitors said that there were more than two million people infected with chikungunya while the government said there were 36,000 cases. As a result of the COVID-19 pandemic, which reached Venezuela in March 2020, costs for services such as internet and telephone lines rose between 80% and 749%, further limiting access to these utilities. Shortages of beds and essential medical equipment, such as latex gloves and antibiotics, have severely limited the capabilities of the country's medical infrastructure. In April 2020 the Venezuelan government asked the Bank of England to sell $US1.02 billion of the Venezuelan gold reserves held by the bank to help the government fund its response to the COVID-19 pandemic. This was followed on 14 May by a legal claim by the Venezuelan Central Bank (BCV) asking the Bank of England to send the proceeds of the sale of gold to the United Nations Development Programme . The claim stated that the funds would then be used to buy healthcare equipment, medicine, and food to address the country's "COVID-19 emergency". The UK Foreign Office had previously agreed to a request from the Trump administration to block the release of Venezuela's gold. In July 2020, the UK High Court ruled that the gold could not be released to the BCV because the UK government recognised Juan Guaidó as the "constitutional interim president of Venezuela". However, in October 2020, an appeals court overturned the High Court decision and asked the UK Foreign Office to clarify who it recognised as president of Venezuela. The Guardian wrote that the position of the UK government was unclear as it "maintains full consular and diplomatic relations with the Venezuela government". [ needs update ]As a result of the COVID-19 pandemic, which reached Venezuela in March 2020, costs for services such as internet and telephone lines rose between 80% and 749%, further limiting access to these utilities. Shortages of beds and essential medical equipment, such as latex gloves and antibiotics, have severely limited the capabilities of the country's medical infrastructure. In April 2020 the Venezuelan government asked the Bank of England to sell $US1.02 billion of the Venezuelan gold reserves held by the bank to help the government fund its response to the COVID-19 pandemic. This was followed on 14 May by a legal claim by the Venezuelan Central Bank (BCV) asking the Bank of England to send the proceeds of the sale of gold to the United Nations Development Programme . The claim stated that the funds would then be used to buy healthcare equipment, medicine, and food to address the country's "COVID-19 emergency". The UK Foreign Office had previously agreed to a request from the Trump administration to block the release of Venezuela's gold. In July 2020, the UK High Court ruled that the gold could not be released to the BCV because the UK government recognised Juan Guaidó as the "constitutional interim president of Venezuela". However, in October 2020, an appeals court overturned the High Court decision and asked the UK Foreign Office to clarify who it recognised as president of Venezuela. The Guardian wrote that the position of the UK government was unclear as it "maintains full consular and diplomatic relations with the Venezuela government". [ needs update ]In 2016, infant mortality increased 30% in one year, to 11,466 deaths of children under the age of one. By 2019, the UN reported that infant mortality had "soared". "Venezuela is the only South American country where infant mortality has returned to levels last seen in the 1990s", according to the HRW/Johns Hopkins report. Maternal mortality also increased 65% in one year, to 756 deaths. Abortion is illegal in Venezuela; the director of a large family planning clinic in Venezuela indicated that more women are arranging for permanent sterilization, and that more are presenting with "complications from clandestine abortions". One of the causes, according to the Venezuelan Association for Alternative Sexual Education, is the severe shortage of oral and injectable contraceptives and intrauterine devices . The HRW/Johns Hopkins report states that the more than 454,000 Venezuelan women who have emigrated to Colombia face 'threats of sexual exploitation and abuse, trafficking, and sexual and reproductive rights violations"; violence based on gender accounted for more than 12% of 2018 health-care events, and indigenous women may be at higher risk. Venezuelan women emigrating are at risk for becoming sex trafficking targets virtually anywhere they flee to. Cases of trafficking in Peru, the United States, Spain, and Colombia display the highest numbers. Due to lack of medical supplies, food and medical care in Venezuelan hospitals, many pregnant women in Venezuela are crossing the border into neighboring countries to give birth. Lack of basic medicine and equipment is causing preventable deaths and maternity is a very high risk for women, especially since there are no blood banks in the event of excessive bleeding. Hospitals frequently have water and electricity outages and only 7% of emergency services are fully operative. Maternal mortality is estimated to have increased by 65% from 2013 to 2016, and unsafe abortions have contributed to 20% of preventable maternal deaths. According to Amnesty International, causes of the increase in maternal deaths include a lack of medical personnel and supplies like anticoagulants, scar healing cream, painkillers, antibiotics, antiseptics, and other tools and equipment. Cúcuta, a city on the Colombian-Venezuela border, has received 14,000 Venezuelan patients at the Erasmo Meoz University Hospital since 2016 and is expecting to receive even more. In this hospital, 75% of the newborns born in the first two months of the year 2019 were Venezuelans. The situation has strained the budget of these hospitals, putting Erasmo Meoz 14 million dollars into debt. While Colombia is the most impacted since it shares a border, women are also traveling to Brazil to give birth. The number of births of Venezuelan babies attended to in Boa Vista, Brazil , has increased from 700 in 2014 to 50,000 in 2017. Venezuelan mothers have also been fleeing to neighboring Peru and Ecuador. For Colombian citizenship it is required that Colombian citizens be born to at least one Colombian parent or be born to foreign parents who meet residence requirements and are eligible to become citizens. Due to the influx of Venezuelan babies being born in Colombia and the Venezuelan government's inability to issue citizenship, Colombia has introduced a new measure that will give these Colombian-born newborns Colombian citizenship to avoid 'statelessness'. The measure went into effect August 2019 and includes babies of Venezuelan parents born in Colombia starting in January 2015, having given citizenship to approximately 27,000 babies born in Colombia over the past four years. Due to lack of medical supplies, food and medical care in Venezuelan hospitals, many pregnant women in Venezuela are crossing the border into neighboring countries to give birth. Lack of basic medicine and equipment is causing preventable deaths and maternity is a very high risk for women, especially since there are no blood banks in the event of excessive bleeding. Hospitals frequently have water and electricity outages and only 7% of emergency services are fully operative. Maternal mortality is estimated to have increased by 65% from 2013 to 2016, and unsafe abortions have contributed to 20% of preventable maternal deaths. According to Amnesty International, causes of the increase in maternal deaths include a lack of medical personnel and supplies like anticoagulants, scar healing cream, painkillers, antibiotics, antiseptics, and other tools and equipment. Cúcuta, a city on the Colombian-Venezuela border, has received 14,000 Venezuelan patients at the Erasmo Meoz University Hospital since 2016 and is expecting to receive even more. In this hospital, 75% of the newborns born in the first two months of the year 2019 were Venezuelans. The situation has strained the budget of these hospitals, putting Erasmo Meoz 14 million dollars into debt. While Colombia is the most impacted since it shares a border, women are also traveling to Brazil to give birth. The number of births of Venezuelan babies attended to in Boa Vista, Brazil , has increased from 700 in 2014 to 50,000 in 2017. Venezuelan mothers have also been fleeing to neighboring Peru and Ecuador. For Colombian citizenship it is required that Colombian citizens be born to at least one Colombian parent or be born to foreign parents who meet residence requirements and are eligible to become citizens. Due to the influx of Venezuelan babies being born in Colombia and the Venezuelan government's inability to issue citizenship, Colombia has introduced a new measure that will give these Colombian-born newborns Colombian citizenship to avoid 'statelessness'. The measure went into effect August 2019 and includes babies of Venezuelan parents born in Colombia starting in January 2015, having given citizenship to approximately 27,000 babies born in Colombia over the past four years. Following the Bolivarian Revolution, the rate of suicide among Venezuelans quadrupled over two decades, with hundreds of thousands of Venezuelans dying from suicide during the period according to the Venezuelan Observatory of Violence. As a result of the crisis, stressors resulting in suicide included economic burden, hunger and loneliness due to the emigration of relatives. In 2015, concerns about shortages and inflation overtook violent crime as Venezuelans' main worry for the first time in years according to pollster Datanálisis. The chief executive of Datanálisis, Luis Vicente Leon, said that Venezuelans had greater concerns over shortages and became preoccupied with the difficulties surrounding them instead. Eldar Shafir , author and American behavioral scientist, said that the psychological "obsession" with finding scarce goods in Venezuela is because the rarity of the item makes it "precious". In 2016, reporters from The New York Times visited six psychiatric wards across the Venezuela at the invitation of doctors; all reported shortages of medicine and even food. In the investigation, they reported that El Pampero Hospital had not employed a psychiatrist in two years, and that it only had running water for only a few hours a day. The hospital, the article said, also suffered from shortages of basic personal-care and cleaning supplies, such as soap, shampoo, toothpaste or toilet paper. The nurses declared that without sedatives, they had to restrain patients or lock them in isolation cells to keep them from harming themselves. The reporters also noted that the government had denied that its public hospitals were suffering from shortages, and had refused multiple offers of international medical aid. Despite the threat of violent protests, the economic crisis affected children more than violence. Abel Saraiba, a psychologist with children's rights organization Cecodap said in 2017, "We have children from a very early age who are having to think about how to survive", with half of her young clients requiring treatment because of the crisis. Children are often forced to stand in food lines or beg with their parents, while the games they play with other children revolve around finding food. Friends of the Child Foundation psychologist Ninoska Zambrano said that children are offering sexual services for food. Zambrano said "Families are doing things that not only lead them to break physically, but in general, socially, we are being morally broken". In 2017, suicide increased by 67% among the elderly and 18% among minors; by 2018, reports emerged of a rapidly increasing suicide rate due to the stressors surrounding the crisis. Mission Barrio Adentro was a program established by Chávez to bring medical care to poor neighborhoods; it was staffed by Cubans that were sent to Venezuela in exchange for petroleum. The New York Times interviewed sixteen Cuban medical professionals in 2019 who had worked for Barrio Adentro prior to the 2018 Venezuelan presidential elections; all sixteen revealed that they were required to participate in voting fraud. Some of the Cubans said that "command centers" for elections were placed near clinics to facilitate "dispatching doctors to pressure residents". Some tactics reported by the Cubans were unrelated to their profession: they were given counterfeit cards to vote even though they were not eligible voters, they witnessed vote tampering when officials opening ballot boxes and destroyed ballots, and they were told to instruct easily manipulated elderly patients in how to vote. But they also "described a system of deliberate political manipulation"; their services as medical professionals "were wielded to secure votes for the governing Socialist Party, often through coercion", they told The New York Times . Facing a shortage of supplies and medicine, they were instructed to withhold treatment–even for emergencies–so supplies and treatment could be "doled out closer to the election, part of a national strategy to compel patients to vote for the government". They reported that life-saving treatment was denied to patients who supported the opposition. As the election neared, they were sent door-to-door, on house visits with a political purpose: "to hand out medicine and enlist voters for Venezuela's Socialist Party". Patients were warned that they could lose their medical care if they did not vote for the socialist party, and that, if Maduro lost, ties would be broken with Cuba, and Venezuelans would lose all medical care. Patients with chronic conditions, at risk of death if they couldn't get medicine, were a particular focus of these tactics. One said that government officials were posing as doctors to make these house calls before elections; 'We, the doctors, were asked to give our extra robes to people. The fake doctors were even giving out medicines, without knowing what they were or how to use them," he said. Since the mid-2000s during Chávez's presidency, Venezuela has had a housing crisis. In 2005, the Venezuelan Construction Chamber (CVC) estimated that there was a shortage of 1.6 million homes, with only 10,000 of 120,000 promised homes constructed by Chávez's government despite billions of dollars in investments. Poor Venezuelans attempted to construct homes on their own despite structural risks. By 2011, there was a housing shortage of 2 million homes, with nearly twenty prime developments being occupied by squatters following Chávez's call for the poor to occupy "unused land". Up to 2011, only 500,000 homes were constructed during the Chávez administration, with over two-thirds of the new housing developments being built by private companies; his government provided about the same amount of housing as previous administrations. Housing shortages were further exacerbated when private construction halted due to the fear of property expropriations and because of the government's inability to construct and provide housing. Urban theorist and author Mike Davis said in July 2011 to The Guardian , "Despite official rhetoric, the Bolivarianist regime has undertaken no serious redistribution of wealth in the cities and oil revenues pay for too many other programmes and subsidies to leave room for new housing construction." By 2012, a shortage of building materials also disrupted construction, with metal production at a 16-year low. By the end of Chávez's presidency in 2013, the number of Venezuelans in inadequate housing had grown to 3 million. Under the Maduro government, housing shortages continued to worsen. Maduro announced in 2014 that due to the shortage of steel, abandoned cars and other vehicles would be acquired by the government and melted to provide rebar for housing. In April 2014, Maduro ruled by decree that Venezuelans who owned three or more rental properties would be forced by the government to sell their rental units at a set price or they would face fines or have their property possessed by the government. By 2016, residents of government-provided housing, who were usually supporters of the government, began protesting due to the lack of utilities and food. Escalating violent crime, especially murder, had been called "perhaps the biggest concern" of Venezuelans during the crisis. Venezuela had "by various measures, the world's highest violent-crime rate" in 2017, and almost none of crimes that were reported were prosecuted. InSight Crime says the crisis has "all too often been obscured by the government's reluctance to release damning crime statistics". The New Yorker reporter found that even stairwells in a public hospital were not safe from robbers, who preyed on staff and patients despite the large number of security forces guarding the hospital, saying this was because the police were assigned to contain journalists who might embarrass the government with exposés on the state of the hospital; they were not assigned to protect its occupants. The police allegedly collaborated with the robbers receiving a cut of what they stole. According to The U.S. Bureau of Diplomatic Security, street gang violence, "corrupt" underpaid police officers, "an inefficient and politicized judicial system", an extremely troubled prison system, and an increased widespread of weaponry has resulted in the majority of criminal activity in Venezuela, with murder being the crime committed the most. The Bureau states that there were 73 daily violent deaths in 2018, and that the government "often attempts to refute or repudiate reports of increasing crime and murder rates; however, independent observers widely reject" the Venezuelan government's claims. The government says there were 60 daily homicides in 2016, and 45 daily in 2015, corresponding with Venezuela's downward economic spiral; the OVV says the numbers are higher. For 2015, the government says the rate of homicides was 70.1 per 100,000 people. The Venezuelan Observatory of Violence (OVV) says the rate was 91.8 homicides per 100,000 people (in 2015, the comparative U.S. number was 4.9 per 100,000 inhabitants). According to the World Bank , the 2016 homicide rate was 56 per 100,000, making Venezuela third in the world, after El Salvador and Honduras. OVV data has 23,047 homicides committed in Venezuela in 2018, a rate of 81.4 per 100,000 people, with the decline being attributed to emigration. According to the Los Angeles Times , ... carjack gangs set up ambushes, sometimes laying down nail-embedded strips to puncture tires of vehicles ferrying potential quarry. Motorists speak matter-of-factly of spotting body parts along roadways. ... While most crime victims are poor, they also include members of the middle and upper classes and scores of police and military personnel killed each year, sometimes for their weapons. ... "Before the thieves would only rob you," is a common refrain here in the capital. "Now they kill you." As a response to the high rate of crime, the Venezuelan government banned private ownership of firearms by some individuals in 2012. El País reported in 2014 that Chávez had years earlier assigned colectivos to be "the armed wing of the Bolivarian Revolution" for the Venezuelan government, giving them weapons, communication systems, motorcycles and surveillance equipment to exercise control in the hills of Caracas where police are forbidden entry. In 2006, they received arms and funding from the state when they were brought under the government's community councils. Chávez eliminated the Metropolitan Police in 2011, turning security over to the colectivos in some Caracas barrios. Some weapons given to the groups include assault rifles , submachine guns and grenades . Despite the Venezuelan government's statements saying that only official authorities can carry weapons for the defense of Venezuela, colectivos are armed with automatic rifles such as AK-47s , submachine guns, fragmentation grenades, and tear gas. During the 2014 Venezuelan protests against Maduro, colectivos acted against the opposition protesters. As the crisis intensified, armed gangs have taken control of cities. The Civil Association for Citizen Control said that more than half of those killed during the protests were killed by colectivos . Human Rights Watch described colectivos as "armed gangs who use violence with impunity" to harass political opponents of the Venezuelan government. Amnesty International calls them "armed pro-government supporters who are tolerated or supported by the authorities". During the 2019 Venezuelan blackouts in March, Maduro called on the armed paramilitary gangs, saying, "The time has come for active resistance". As blackouts continued, on 31 March, citizens protested the lack of electricity and water in Caracas and other cities; Maduro called again on the colectivos, asking them "to defend the peace of every barrio, of every block". Videos circulated on social media showing colectivos threatening protesters and shooting in the streets; two protestors were shot. There is no reliable data on kidnapping in Venezuela and available data is considered an underestimate; it is against the law to pay ransom, and according to criminologists, at least 80% of kidnappings are not reported for fear of retaliation, or because relatives prefer to negotiate, hoping the hostage will be released and fearing they will be killed if authorities are contacted. Available data underestimates the amount of express kidnapping , where victims are typically released in less than two days after relatives pay a quick ransom. Most express kidnapping victims are released, but in 2016, 18 were killed. At least 80% of kidnappings occur in a limited area around Caracas and including Miranda State . In the areas where most kidnappings occur, the government set up so-called "peace zones" where official police withdrew and gangs took over; "experts say the government has armed these groups ... [who] ... control large territories, financed through extortion and the drug trade". Illegal mining creates pools of standing water that encourage mosquito breeding, a partial cause of the increase in malaria seen in Venezuela. The murder rate in Venezuela had also decreased significantly between 2017 and 2019. In 2018, Venezuela's murder rate–described as the highest in the world–had begun to decrease to 81.4 per 100,000 people according to the Venezuelan Violence Observatory (OVV), with the organization stating that this downward trend was due to the millions of Venezuelans that emigrated from the country at the time. The murder rate declined even further to 60.3 in 2019. Repression and politically motivated detentions have risen to record levels in 2019. Foro Penal states that Venezuela has at least 900 political prisoners as of April 2019, with more arrests of people being held longer in poor conditions and on dubious charges. The human rights organization has documented more than 50 instances that include "sexual abuse, strangulation using plastic bags and the use of razor blades to cut detainees' feet". In the first three months of 2019, Foro Penal says 1,712 people were arrested and about two-thirds of those were held for more than 48 hours, the threshold used to classify a detainee as a political prisoner. Maduro calls those arrested members of "terrorist groups" and says his government will not hesitate to send them to prison. Juan Requesens and Roberto Marrero are examples of "purely political" arrests, according to their attorney. Increasingly high numbers of the detainees are working-class people, who have been driven to protest by the crisis. The final published report addressed the extrajudicial executions, torture, forced disappearances and other human rights violations reportedly committed by Venezuelan security forces in the recent years. Bachelet expressed her concerns for the "shockingly high" number of extrajudicial killings and urged for the dissolution of the FAES. According to the report, 1,569 cases of executions as consequence as a result of "resistance to authority" were registered by the Venezuelan authorities from 1 January to 19 March. Other 52 deaths that occurred during 2019 protests were attributed to colectivos. The report also details how the Venezuelan government "aimed at neutralising, repressing and criminalising political opponents and people critical of the government" since 2016. On 16 September 2020, the United Nations Fact Finding Mission on Venezuela accused the Maduro government of crimes against humanity . On 15 February 2024, the Maduro government closed the UN High Commissioner for Human Rights office in Caracas after High Commissioner Volker Türk condemned the detention of activist Rocío San Miguel , demanding "her immediate release and respect for her right to legal defense". Maduro's government expelled its officials, giving them 72 hours to leave the country. The exodus of millions of desperate impoverished Venezuelans to surrounding countries has been called "a risk for the entire region". Millions of Venezuelan people have voluntarily emigrated from Venezuela during the Chávez and Maduro presidencies. The crisis started during the Chávez presidency, but became much more pronounced during Maduro's term. Emigration has been motivated by economic collapse, expansion of state control over the economy , high crime, high inflation, general uncertainty, a lack of hope for a change in government, a failing public sector, and "shortages of basic necessities". The PGA Group estimates more than 1.5 million Venezuelans emigrated in the 15 years between 1999 and 2014; an estimated 1.8 million left in ten years through 2015. The UN said that in the first part of 2018, about 5,000 Venezuelans were leaving Venezuela daily. A February 2019 UN reported estimated that 3.4 million Venezuelans have emigrated, and they expect another 1.9 million may emigrate in 2019. The UN estimates 2.7 million have gone to the Caribbean and Latin America. Most have gone to Colombia; estimates of Venezuelans emigrating to Colombia are 1.1 million, Peru 506,000, Chile 288,000, Ecuador 221,000, Argentina 130,000, and Brazil 96,000. This is in contrast to Venezuela's high immigration rate during the 20th century. Kevin Whitaker, the U.S. ambassador in Colombia, says, "Colombians, in their tens and hundreds of thousands, migrated to Venezuela in the '60s and '70s and '80s, when Venezuela was a wealthy country and Colombia was not so much. Now, more than 1 million Venezuelans, many of them since 2015, have gone to live in Colombia." Those who leave by foot are known as los caminantes (the walkers); the walk to Bogotá, Colombia is 560 kilometres (350 mi) , and some walk hundreds of kilometres further, to Ecuador or Peru. Alba Pereira, who helps feed and clothe about 800 walkers daily in Northern Colombia, said in 2019 she is seeing more sick, elderly and pregnant among the walkers. The Colombian Red Cross has set up rest tents with food and water on the side of the roads for Venezuelans. Venezuelans also cross into northern Brazil, where UNHCR has set up 10 shelters to house thousands of Venezuelans. Images of Venezuelans fleeing the country by sea have raised symbolic comparisons to the images seen from the Cuban diaspora . In 1998, only 14 Venezuelans were granted U.S. asylum, and by September 1999, 1,086 Venezuelans were granted asylum according to the U.S. Citizenship and Immigration Services . The first wave of Venezuelan emigrants were wealthy and middle class Venezuelans concerned by Chávez's rhetoric of redistributing wealth to the poor; the early exodus of college-educated people with capital caused a brain drain . Emigration especially increased during the Maduro presidency. This second wave of emigration consisted of lower class Venezuelans suffering directly from the economic crisis facing the country; thus, the same individuals whom Chávez attempted to aid were now seeking to emigrate, driven by worsening economic conditions, scarcity of food and medicine, and rising rates of violent crime. Tomás Pérez, who studies the Venezuelan diaspora at the Central University of Venezuela, said in 2018 that because "now everyone is poor", it is mostly poor leaving the country. Carlos Malamud, from a Spanish think tank, said Maduro is "using migration as a political weapon against the opposition". The scale of the crisis has surpassed in four years the Cuban exodus, in which 1.7 million emigrated over a period of sixty years; Malamud says "Latin American societies aren't prepared for such wide-scale arrivals". Impacting the health care crisis in Venezuela, health care professionals are emigrating; a primary factor driving emigration to Colombia is the lack of "medicines, supplies, health providers, and basic health services" in Venezuela. Since 2017, the banking sector has seen 18,000 employees leave the country. Escalating violent crime, especially murder, had been called "perhaps the biggest concern" of Venezuelans during the crisis. Venezuela had "by various measures, the world's highest violent-crime rate" in 2017, and almost none of crimes that were reported were prosecuted. InSight Crime says the crisis has "all too often been obscured by the government's reluctance to release damning crime statistics". The New Yorker reporter found that even stairwells in a public hospital were not safe from robbers, who preyed on staff and patients despite the large number of security forces guarding the hospital, saying this was because the police were assigned to contain journalists who might embarrass the government with exposés on the state of the hospital; they were not assigned to protect its occupants. The police allegedly collaborated with the robbers receiving a cut of what they stole. According to The U.S. Bureau of Diplomatic Security, street gang violence, "corrupt" underpaid police officers, "an inefficient and politicized judicial system", an extremely troubled prison system, and an increased widespread of weaponry has resulted in the majority of criminal activity in Venezuela, with murder being the crime committed the most. The Bureau states that there were 73 daily violent deaths in 2018, and that the government "often attempts to refute or repudiate reports of increasing crime and murder rates; however, independent observers widely reject" the Venezuelan government's claims. The government says there were 60 daily homicides in 2016, and 45 daily in 2015, corresponding with Venezuela's downward economic spiral; the OVV says the numbers are higher. For 2015, the government says the rate of homicides was 70.1 per 100,000 people. The Venezuelan Observatory of Violence (OVV) says the rate was 91.8 homicides per 100,000 people (in 2015, the comparative U.S. number was 4.9 per 100,000 inhabitants). According to the World Bank , the 2016 homicide rate was 56 per 100,000, making Venezuela third in the world, after El Salvador and Honduras. OVV data has 23,047 homicides committed in Venezuela in 2018, a rate of 81.4 per 100,000 people, with the decline being attributed to emigration. According to the Los Angeles Times , ... carjack gangs set up ambushes, sometimes laying down nail-embedded strips to puncture tires of vehicles ferrying potential quarry. Motorists speak matter-of-factly of spotting body parts along roadways. ... While most crime victims are poor, they also include members of the middle and upper classes and scores of police and military personnel killed each year, sometimes for their weapons. ... "Before the thieves would only rob you," is a common refrain here in the capital. "Now they kill you." As a response to the high rate of crime, the Venezuelan government banned private ownership of firearms by some individuals in 2012. El País reported in 2014 that Chávez had years earlier assigned colectivos to be "the armed wing of the Bolivarian Revolution" for the Venezuelan government, giving them weapons, communication systems, motorcycles and surveillance equipment to exercise control in the hills of Caracas where police are forbidden entry. In 2006, they received arms and funding from the state when they were brought under the government's community councils. Chávez eliminated the Metropolitan Police in 2011, turning security over to the colectivos in some Caracas barrios. Some weapons given to the groups include assault rifles , submachine guns and grenades . Despite the Venezuelan government's statements saying that only official authorities can carry weapons for the defense of Venezuela, colectivos are armed with automatic rifles such as AK-47s , submachine guns, fragmentation grenades, and tear gas. During the 2014 Venezuelan protests against Maduro, colectivos acted against the opposition protesters. As the crisis intensified, armed gangs have taken control of cities. The Civil Association for Citizen Control said that more than half of those killed during the protests were killed by colectivos . Human Rights Watch described colectivos as "armed gangs who use violence with impunity" to harass political opponents of the Venezuelan government. Amnesty International calls them "armed pro-government supporters who are tolerated or supported by the authorities". During the 2019 Venezuelan blackouts in March, Maduro called on the armed paramilitary gangs, saying, "The time has come for active resistance". As blackouts continued, on 31 March, citizens protested the lack of electricity and water in Caracas and other cities; Maduro called again on the colectivos, asking them "to defend the peace of every barrio, of every block". Videos circulated on social media showing colectivos threatening protesters and shooting in the streets; two protestors were shot. There is no reliable data on kidnapping in Venezuela and available data is considered an underestimate; it is against the law to pay ransom, and according to criminologists, at least 80% of kidnappings are not reported for fear of retaliation, or because relatives prefer to negotiate, hoping the hostage will be released and fearing they will be killed if authorities are contacted. Available data underestimates the amount of express kidnapping , where victims are typically released in less than two days after relatives pay a quick ransom. Most express kidnapping victims are released, but in 2016, 18 were killed. At least 80% of kidnappings occur in a limited area around Caracas and including Miranda State . In the areas where most kidnappings occur, the government set up so-called "peace zones" where official police withdrew and gangs took over; "experts say the government has armed these groups ... [who] ... control large territories, financed through extortion and the drug trade". Illegal mining creates pools of standing water that encourage mosquito breeding, a partial cause of the increase in malaria seen in Venezuela. The murder rate in Venezuela had also decreased significantly between 2017 and 2019. In 2018, Venezuela's murder rate–described as the highest in the world–had begun to decrease to 81.4 per 100,000 people according to the Venezuelan Violence Observatory (OVV), with the organization stating that this downward trend was due to the millions of Venezuelans that emigrated from the country at the time. The murder rate declined even further to 60.3 in 2019. Repression and politically motivated detentions have risen to record levels in 2019. Foro Penal states that Venezuela has at least 900 political prisoners as of April 2019, with more arrests of people being held longer in poor conditions and on dubious charges. The human rights organization has documented more than 50 instances that include "sexual abuse, strangulation using plastic bags and the use of razor blades to cut detainees' feet". In the first three months of 2019, Foro Penal says 1,712 people were arrested and about two-thirds of those were held for more than 48 hours, the threshold used to classify a detainee as a political prisoner. Maduro calls those arrested members of "terrorist groups" and says his government will not hesitate to send them to prison. Juan Requesens and Roberto Marrero are examples of "purely political" arrests, according to their attorney. Increasingly high numbers of the detainees are working-class people, who have been driven to protest by the crisis. The final published report addressed the extrajudicial executions, torture, forced disappearances and other human rights violations reportedly committed by Venezuelan security forces in the recent years. Bachelet expressed her concerns for the "shockingly high" number of extrajudicial killings and urged for the dissolution of the FAES. According to the report, 1,569 cases of executions as consequence as a result of "resistance to authority" were registered by the Venezuelan authorities from 1 January to 19 March. Other 52 deaths that occurred during 2019 protests were attributed to colectivos. The report also details how the Venezuelan government "aimed at neutralising, repressing and criminalising political opponents and people critical of the government" since 2016. On 16 September 2020, the United Nations Fact Finding Mission on Venezuela accused the Maduro government of crimes against humanity . On 15 February 2024, the Maduro government closed the UN High Commissioner for Human Rights office in Caracas after High Commissioner Volker Türk condemned the detention of activist Rocío San Miguel , demanding "her immediate release and respect for her right to legal defense". Maduro's government expelled its officials, giving them 72 hours to leave the country. The exodus of millions of desperate impoverished Venezuelans to surrounding countries has been called "a risk for the entire region". Millions of Venezuelan people have voluntarily emigrated from Venezuela during the Chávez and Maduro presidencies. The crisis started during the Chávez presidency, but became much more pronounced during Maduro's term. Emigration has been motivated by economic collapse, expansion of state control over the economy , high crime, high inflation, general uncertainty, a lack of hope for a change in government, a failing public sector, and "shortages of basic necessities". The PGA Group estimates more than 1.5 million Venezuelans emigrated in the 15 years between 1999 and 2014; an estimated 1.8 million left in ten years through 2015. The UN said that in the first part of 2018, about 5,000 Venezuelans were leaving Venezuela daily. A February 2019 UN reported estimated that 3.4 million Venezuelans have emigrated, and they expect another 1.9 million may emigrate in 2019. The UN estimates 2.7 million have gone to the Caribbean and Latin America. Most have gone to Colombia; estimates of Venezuelans emigrating to Colombia are 1.1 million, Peru 506,000, Chile 288,000, Ecuador 221,000, Argentina 130,000, and Brazil 96,000. This is in contrast to Venezuela's high immigration rate during the 20th century. Kevin Whitaker, the U.S. ambassador in Colombia, says, "Colombians, in their tens and hundreds of thousands, migrated to Venezuela in the '60s and '70s and '80s, when Venezuela was a wealthy country and Colombia was not so much. Now, more than 1 million Venezuelans, many of them since 2015, have gone to live in Colombia." Those who leave by foot are known as los caminantes (the walkers); the walk to Bogotá, Colombia is 560 kilometres (350 mi) , and some walk hundreds of kilometres further, to Ecuador or Peru. Alba Pereira, who helps feed and clothe about 800 walkers daily in Northern Colombia, said in 2019 she is seeing more sick, elderly and pregnant among the walkers. The Colombian Red Cross has set up rest tents with food and water on the side of the roads for Venezuelans. Venezuelans also cross into northern Brazil, where UNHCR has set up 10 shelters to house thousands of Venezuelans. Images of Venezuelans fleeing the country by sea have raised symbolic comparisons to the images seen from the Cuban diaspora . In 1998, only 14 Venezuelans were granted U.S. asylum, and by September 1999, 1,086 Venezuelans were granted asylum according to the U.S. Citizenship and Immigration Services . The first wave of Venezuelan emigrants were wealthy and middle class Venezuelans concerned by Chávez's rhetoric of redistributing wealth to the poor; the early exodus of college-educated people with capital caused a brain drain . Emigration especially increased during the Maduro presidency. This second wave of emigration consisted of lower class Venezuelans suffering directly from the economic crisis facing the country; thus, the same individuals whom Chávez attempted to aid were now seeking to emigrate, driven by worsening economic conditions, scarcity of food and medicine, and rising rates of violent crime. Tomás Pérez, who studies the Venezuelan diaspora at the Central University of Venezuela, said in 2018 that because "now everyone is poor", it is mostly poor leaving the country. Carlos Malamud, from a Spanish think tank, said Maduro is "using migration as a political weapon against the opposition". The scale of the crisis has surpassed in four years the Cuban exodus, in which 1.7 million emigrated over a period of sixty years; Malamud says "Latin American societies aren't prepared for such wide-scale arrivals". Impacting the health care crisis in Venezuela, health care professionals are emigrating; a primary factor driving emigration to Colombia is the lack of "medicines, supplies, health providers, and basic health services" in Venezuela. Since 2017, the banking sector has seen 18,000 employees leave the country. Maduro's government stopped releasing social and economic indicators, so most data rely on estimates. The Institute of International Finance (IIF) stated in March 2019 that "Venezuela's economic collapse is among the world's worst in recent history". A chief economist of the IIF said the crisis resulted from "policy decisions, economic mismanagement, and political turmoil", saying it is on a scale that "one would only expect from extreme natural disasters or military confrontations". The April 2019 International Monetary Fund (IMF) World Economic Outlook described Venezuela as being in a "wartime economy". For the fifth consecutive year, Bloomberg rated Venezuela last on its misery index in 2019. The government's main source of income is oil, with output "plummeting due to lack of investment, poor maintenance and neglect", from which consultant Eduardo Fortuny expects will take 12 years to recover. As of 2020 the Venezuelan government has liberalized many socialist or redistributive economic policies—price and currency controls, stringent labor laws—and brought a rapprochement with members of the local business community—especially Lorenzo Mendoza of the iconic Empresas Polar conglomerate (who is no longer denounced as a "thief," a "parasite" and a "traitor"), in exchange for an abandonment of political opposition by Mendoza. However, a "slight recovery" in economic activity in January 2020 reportedly "evaporated in February and March" due to "the fall in global oil prices and the coronavirus pandemic". A number of foreign firms have left the nation—often due to quarrels with the socialist government—including Smurfit Kappa , Clorox , Kimberly Clark and General Mills ; the departures aggravate unemployment and shortages. Before the effects of the 2019 Venezuelan blackouts, the number of multinational companies in the industrial city of Valencia in Carabobo State had dropped from 5,000 when Chávez became president to a tenth of that. Domestic airlines are having difficulties because of hyperinflation and parts shortages, and most international airlines have left the country . Airlines from many countries ceased operating in Venezuela, making travel to the country difficult: Air Canada became the first international airline to cease Venezuela operations in March 2014 and was followed by Alitalia in April 2015. Other airlines that have left are Aeroméxico , Avianca , Delta , Lufthansa , LATAM , and United Airlines . According to the International Air Transport Association (IATA), the government of Venezuela has not paid US$3.8 billion to international airlines in an issue involving conversion of local currency to U.S. dollars. Airlines have left for other reasons, including crime against flight crews and foreign passengers, stolen baggage, and problems with the quality of jet fuel and maintenance of runways. Aerolíneas Argentinas left in 2017, citing security reasons, and American Airlines , the last U.S. airline serving Venezuela, left on 15 March 2019, after its pilots refused to fly to Venezuela, citing safety issues. Currently, the only North American airline flying to Venezuela is Sunwing Airlines , with seasonal service to Margarita Island and Punto Fijo . [ citation needed ] Following the increasing economic partnership between Venezuela and Turkey in October 2016, Turkish Airlines started offering direct flights from December 2016 connecting between Caracas to Istanbul (via Havana, Cuba) in an effort to "link and expand contacts" between the two countries. Iranian airline Mahan Air (blacklisted by the U.S. government since 2011 ) began direct flights to Caracas in April 2019, "signifying a growing relationship between the two nations" according to Fox News . In May 2019, the United States Department of Transport and Department of Homeland Security suspended all flights between Venezuela and the United States, due to safety and security concerns. The suspension affects mainly Venezuelan airlines flying to Miami , which are Avior Airlines , LASER Airlines and Estelar Latinoamérica . Estimated to drop by 25% in 2019, the IMF said the contraction in Venezuela's GDP—the largest since the Libyan Civil War began in 2014—was affecting all of Latin America. In 2015 the Venezuelan economy contracted 5.7% and in 2016 it contracted 18.6% according to the Venezuelan central bank; after that, the government stopped producing data. Ecoanalítica, a Venezuelan consultant, told The Wall Street Journal that output had halved between 2016 and 2019. The IMF and AGPV Asesores Económicos, a consulting firm based in Caracas, estimate that GDP shrunk to $80 billion in 2018 from $196 billion in 2013, making the economy smaller than Guatemala's or Ethiopia's. The annual inflation rate for consumer prices has risen hundreds of thousands of percent during the crisis. Inflation in Venezuela remained high during Chávez's presidency. By 2010, inflation removed any advancement of wage increases, and by 2014 at 69% it was the highest in the world. In November 2016, Venezuela entered a period of hyperinflation , with inflation reaching 4,000% in 2017; the Venezuelan government "essentially stopped" producing inflation estimates in early 2018. At the end of 2018, inflation had reached 1.35 million percent. In the 2017 Christmas season, some shops stopped using price tags since prices would inflate so quickly. From 2017 to 2019, some Venezuelans became video game gold farmers and could be seen playing games such as RuneScape to sell in-game currency or characters for real currency; players could make more money than salaried workers by earning only a few dollars per day. Some of these "gold farmers" will use cryptocurrencies as an intermediary currency before converting into Bolivares, as indicated in this interview . In October 2018, the IMF estimated that inflation would reach 10,000,000% by the end of 2019. In early 2019, the monthly minimum salary was the equivalent of US$5.50 (18,000 sovereign bolivars)—less than the price of a Happy Meal at McDonald's. Ecoanalitica estimated that prices jumped by 465% in the first two-and-a-half months of 2019. The Wall Street Journal stated in March 2019 that the "main cause of hyperinflation is the central bank printing money to increase money supply, thus boosting domestic spending.", reporting that a teacher can buy a dozen eggs and two pounds of cheese with a month's wages. In May 2019, the Central Bank of Venezuela released economic data for the first time since 2015. According to the release, Venezuela's inflation rate was 274% in 2016, 863% in 2017 and 130,060% in 2018. The new reports imply a contraction of more than half of the economy in five years, according to the Financial Times "one of the biggest contractions in Latin American history". Sources quoted by Reuters, said that China may have asked Venezuela to release the data to bring Venezuela into compliance with the IMF and make it more difficult for the IMF to recognise Juan Guaidó during the presidential crisis. The IMF said it was not able to assess the quality of the data as it had no contact with the Venezuelan government. Shortages in Venezuela became prevalent after price controls were enacted according to the economic policy of the Hugo Chávez government. Under the economic policy of the Nicolás Maduro government , greater shortages occurred due to the Venezuelan government's policy of withholding United States dollars from importers with price controls. Some Venezuelans must search for food—occasionally resorting to eating wild fruit or garbage—wait in lines for hours and sometimes settle without having certain products. [Venezuela's wartime economy has the] world's highest unemployment since end of Bosnian War in world's biggest contraction since 2014 start of Libyan Civil War April 2019 International Monetary Fund (IMF) World Economic Outlook In January 2016 the unemployment rate was 18.1 percent and the economy was the worst in the world according to the misery index. Venezuela has not reported official unemployment figures since April 2016, when the rate was at 7.3 percent. Unemployment was forecasted to reach 44% for 2019; the IMF stated that this was the highest unemployment seen since the end of the Bosnian War in 1995. In August 2017 President of the United States Donald Trump imposed sanctions on Venezuela which banned transactions involving Venezuela's state debt including debt restructuring. The technical default period ended 13 November 2017 and Venezuela did not pay coupons on its dollar eurobonds, causing a cross-default on other dollar bonds. A committee consisting of the fifteen largest banks admitted default on state debt obligations which in turn entailed payments on CDS on 30 November. In November 2017, The Economist estimated Venezuela's debt at US$105 billion and its reserves at US$10 billion. In 2018, Venezuela's debt grew to US$156 billion and as of March 2019, its reserves had dropped to US$8 billion. With the exception of PDVSA's 2020 bonds, as of January 2019, all of Venezuela's bonds are in default, and Venezuela's government and state-owned companies owe nearly US$8 billion in unpaid interest and principal. As of March 2019, the government and state-owned companies have US$150 billion in debt. By 2018 the political and economic troubles facing Venezuela had engulfed the El Tigre - San Tomé region, a key region for oil production in eastern Venezuela. Oil workers were fleeing the state-owned oil company as salaries could not keep up with hyperinflation, reducing families to starvation. Workers and criminals stripped vital oil industry equipment of anything valuable, ranging from pickup trucks to the copper wire within critical oil production components. Oil facilities were neglected and unprotected, crippling oil production and leading to environmental damage . As noted petroleum historian, expert, and former San Tomé resident Emma Brossard stated in 2005, "Venezuelan oil fields had a depletion rate of 25 per cent annually [and] there had to be an investment of US$3.4 billion a year to keep up its production." "But since Chávez has become president there has been no investment." As of 2020 there were no longer any oil rigs searching for oil in Venezuela, and production has been "reduced to a trickle". Oil exports are expected to total $2.3 billion for 2020, continuing a decline of more than a decade. Pollution from crude oil leaking from abandoned underwater wells and pipelines has caused serious damage to fishing and human health. In 2022, rising oil prices caused by the Russian invasion of Ukraine led the World Oil Commission to start meetings with the Venezuelan Government to push oil production to have a control over the price. [ citation needed ]A number of foreign firms have left the nation—often due to quarrels with the socialist government—including Smurfit Kappa , Clorox , Kimberly Clark and General Mills ; the departures aggravate unemployment and shortages. Before the effects of the 2019 Venezuelan blackouts, the number of multinational companies in the industrial city of Valencia in Carabobo State had dropped from 5,000 when Chávez became president to a tenth of that. Domestic airlines are having difficulties because of hyperinflation and parts shortages, and most international airlines have left the country . Airlines from many countries ceased operating in Venezuela, making travel to the country difficult: Air Canada became the first international airline to cease Venezuela operations in March 2014 and was followed by Alitalia in April 2015. Other airlines that have left are Aeroméxico , Avianca , Delta , Lufthansa , LATAM , and United Airlines . According to the International Air Transport Association (IATA), the government of Venezuela has not paid US$3.8 billion to international airlines in an issue involving conversion of local currency to U.S. dollars. Airlines have left for other reasons, including crime against flight crews and foreign passengers, stolen baggage, and problems with the quality of jet fuel and maintenance of runways. Aerolíneas Argentinas left in 2017, citing security reasons, and American Airlines , the last U.S. airline serving Venezuela, left on 15 March 2019, after its pilots refused to fly to Venezuela, citing safety issues. Currently, the only North American airline flying to Venezuela is Sunwing Airlines , with seasonal service to Margarita Island and Punto Fijo . [ citation needed ] Following the increasing economic partnership between Venezuela and Turkey in October 2016, Turkish Airlines started offering direct flights from December 2016 connecting between Caracas to Istanbul (via Havana, Cuba) in an effort to "link and expand contacts" between the two countries. Iranian airline Mahan Air (blacklisted by the U.S. government since 2011 ) began direct flights to Caracas in April 2019, "signifying a growing relationship between the two nations" according to Fox News . In May 2019, the United States Department of Transport and Department of Homeland Security suspended all flights between Venezuela and the United States, due to safety and security concerns. The suspension affects mainly Venezuelan airlines flying to Miami , which are Avior Airlines , LASER Airlines and Estelar Latinoamérica .Domestic airlines are having difficulties because of hyperinflation and parts shortages, and most international airlines have left the country . Airlines from many countries ceased operating in Venezuela, making travel to the country difficult: Air Canada became the first international airline to cease Venezuela operations in March 2014 and was followed by Alitalia in April 2015. Other airlines that have left are Aeroméxico , Avianca , Delta , Lufthansa , LATAM , and United Airlines . According to the International Air Transport Association (IATA), the government of Venezuela has not paid US$3.8 billion to international airlines in an issue involving conversion of local currency to U.S. dollars. Airlines have left for other reasons, including crime against flight crews and foreign passengers, stolen baggage, and problems with the quality of jet fuel and maintenance of runways. Aerolíneas Argentinas left in 2017, citing security reasons, and American Airlines , the last U.S. airline serving Venezuela, left on 15 March 2019, after its pilots refused to fly to Venezuela, citing safety issues. Currently, the only North American airline flying to Venezuela is Sunwing Airlines , with seasonal service to Margarita Island and Punto Fijo . [ citation needed ] Following the increasing economic partnership between Venezuela and Turkey in October 2016, Turkish Airlines started offering direct flights from December 2016 connecting between Caracas to Istanbul (via Havana, Cuba) in an effort to "link and expand contacts" between the two countries. Iranian airline Mahan Air (blacklisted by the U.S. government since 2011 ) began direct flights to Caracas in April 2019, "signifying a growing relationship between the two nations" according to Fox News . In May 2019, the United States Department of Transport and Department of Homeland Security suspended all flights between Venezuela and the United States, due to safety and security concerns. The suspension affects mainly Venezuelan airlines flying to Miami , which are Avior Airlines , LASER Airlines and Estelar Latinoamérica .Estimated to drop by 25% in 2019, the IMF said the contraction in Venezuela's GDP—the largest since the Libyan Civil War began in 2014—was affecting all of Latin America. In 2015 the Venezuelan economy contracted 5.7% and in 2016 it contracted 18.6% according to the Venezuelan central bank; after that, the government stopped producing data. Ecoanalítica, a Venezuelan consultant, told The Wall Street Journal that output had halved between 2016 and 2019. The IMF and AGPV Asesores Económicos, a consulting firm based in Caracas, estimate that GDP shrunk to $80 billion in 2018 from $196 billion in 2013, making the economy smaller than Guatemala's or Ethiopia's. The annual inflation rate for consumer prices has risen hundreds of thousands of percent during the crisis. Inflation in Venezuela remained high during Chávez's presidency. By 2010, inflation removed any advancement of wage increases, and by 2014 at 69% it was the highest in the world. In November 2016, Venezuela entered a period of hyperinflation , with inflation reaching 4,000% in 2017; the Venezuelan government "essentially stopped" producing inflation estimates in early 2018. At the end of 2018, inflation had reached 1.35 million percent. In the 2017 Christmas season, some shops stopped using price tags since prices would inflate so quickly. From 2017 to 2019, some Venezuelans became video game gold farmers and could be seen playing games such as RuneScape to sell in-game currency or characters for real currency; players could make more money than salaried workers by earning only a few dollars per day. Some of these "gold farmers" will use cryptocurrencies as an intermediary currency before converting into Bolivares, as indicated in this interview . In October 2018, the IMF estimated that inflation would reach 10,000,000% by the end of 2019. In early 2019, the monthly minimum salary was the equivalent of US$5.50 (18,000 sovereign bolivars)—less than the price of a Happy Meal at McDonald's. Ecoanalitica estimated that prices jumped by 465% in the first two-and-a-half months of 2019. The Wall Street Journal stated in March 2019 that the "main cause of hyperinflation is the central bank printing money to increase money supply, thus boosting domestic spending.", reporting that a teacher can buy a dozen eggs and two pounds of cheese with a month's wages. In May 2019, the Central Bank of Venezuela released economic data for the first time since 2015. According to the release, Venezuela's inflation rate was 274% in 2016, 863% in 2017 and 130,060% in 2018. The new reports imply a contraction of more than half of the economy in five years, according to the Financial Times "one of the biggest contractions in Latin American history". Sources quoted by Reuters, said that China may have asked Venezuela to release the data to bring Venezuela into compliance with the IMF and make it more difficult for the IMF to recognise Juan Guaidó during the presidential crisis. The IMF said it was not able to assess the quality of the data as it had no contact with the Venezuelan government. Shortages in Venezuela became prevalent after price controls were enacted according to the economic policy of the Hugo Chávez government. Under the economic policy of the Nicolás Maduro government , greater shortages occurred due to the Venezuelan government's policy of withholding United States dollars from importers with price controls. Some Venezuelans must search for food—occasionally resorting to eating wild fruit or garbage—wait in lines for hours and sometimes settle without having certain products. [Venezuela's wartime economy has the] world's highest unemployment since end of Bosnian War in world's biggest contraction since 2014 start of Libyan Civil War April 2019 International Monetary Fund (IMF) World Economic Outlook In January 2016 the unemployment rate was 18.1 percent and the economy was the worst in the world according to the misery index. Venezuela has not reported official unemployment figures since April 2016, when the rate was at 7.3 percent. Unemployment was forecasted to reach 44% for 2019; the IMF stated that this was the highest unemployment seen since the end of the Bosnian War in 1995. In August 2017 President of the United States Donald Trump imposed sanctions on Venezuela which banned transactions involving Venezuela's state debt including debt restructuring. The technical default period ended 13 November 2017 and Venezuela did not pay coupons on its dollar eurobonds, causing a cross-default on other dollar bonds. A committee consisting of the fifteen largest banks admitted default on state debt obligations which in turn entailed payments on CDS on 30 November. In November 2017, The Economist estimated Venezuela's debt at US$105 billion and its reserves at US$10 billion. In 2018, Venezuela's debt grew to US$156 billion and as of March 2019, its reserves had dropped to US$8 billion. With the exception of PDVSA's 2020 bonds, as of January 2019, all of Venezuela's bonds are in default, and Venezuela's government and state-owned companies owe nearly US$8 billion in unpaid interest and principal. As of March 2019, the government and state-owned companies have US$150 billion in debt. By 2018 the political and economic troubles facing Venezuela had engulfed the El Tigre - San Tomé region, a key region for oil production in eastern Venezuela. Oil workers were fleeing the state-owned oil company as salaries could not keep up with hyperinflation, reducing families to starvation. Workers and criminals stripped vital oil industry equipment of anything valuable, ranging from pickup trucks to the copper wire within critical oil production components. Oil facilities were neglected and unprotected, crippling oil production and leading to environmental damage . As noted petroleum historian, expert, and former San Tomé resident Emma Brossard stated in 2005, "Venezuelan oil fields had a depletion rate of 25 per cent annually [and] there had to be an investment of US$3.4 billion a year to keep up its production." "But since Chávez has become president there has been no investment." As of 2020 there were no longer any oil rigs searching for oil in Venezuela, and production has been "reduced to a trickle". Oil exports are expected to total $2.3 billion for 2020, continuing a decline of more than a decade. Pollution from crude oil leaking from abandoned underwater wells and pipelines has caused serious damage to fishing and human health. In 2022, rising oil prices caused by the Russian invasion of Ukraine led the World Oil Commission to start meetings with the Venezuelan Government to push oil production to have a control over the price. [ citation needed ]A November 2016 Datincorp survey that asked Venezuelans living in urban areas which entity was responsible for the crisis, 59% blamed chavismo or the presidents (Chávez, 25%; Maduro 19%; Chavismo 15%) while others blamed the opposition (10%), entrepreneurs (4%) and the United States (2%). A September 2018 Meganálisis survey found that 85% of Venezuelans wanted Maduro to leave power immediately. A November 2018 Datanálisis poll found that 54% of Venezuelans opposed a foreign military intervention to remove Maduro, while 35% supported an intervention. Instead, 63% supported a "negotiated settlement to remove Maduro". An 11–14 March 2019 survey of 1,100 people in 16 Venezuelan states and 32 cities by Meganálisis found that 89% of respondents wanted Maduro to leave the presidency. A Datanálisis poll on 4 March 2019 found Maduro's approval rating at an all-time low of 14%. According to Datanálisis, in early 2019, 63% of Venezuelans believed that a change of government was possible. Fourteen months later, in May 2020, after the Macuto Bay raid , the percentage decreased to 20%. According to economists interviewed by The New York Times , the situation is by far the worst economic crisis in Venezuela's history, and is also the worst facing a country in peace time since the mid-20th century. The crisis is also more severe than that of the United States during the Great Depression , the 1985–1994 Brazilian economic crisis , or the 2008–2009 hyperinflation in Zimbabwe . Other writers have also compared aspects of the crisis, such as unemployment and GDP contraction, to that of Bosnia and Herzegovina after the 1992–1995 Bosnian War , and those in Russia , Cuba and Albania following the collapse of the Eastern Bloc in 1989 and the dissolution of the Soviet Union in 1991. The European Union, the Lima Group, the United States and other countries have applied individual sanctions against government officials and members of both the military and security forces as a response to human rights violations, corruption, degradation in the rule of law and repression of democracy . The United States would later extend its sanctions to the petroleum sector. Economists have stated that shortages and high inflation in Venezuela began before US sanctions were directed towards the country. The Wall Street Journal said that economists place the blame for Venezuela's economy shrinking by half on "Maduro's policies, including widespread nationalizations, out-of-control spending that sparked inflation, price controls that led to shortages, and widespread graft and mismanagement." The Venezuelan government has stated that the United States is responsible for its economic collapse. The HRW/Johns Hopkins report noted that most sanctions are "limited to canceling visas and freezing assets of key officials implicated in abuses and corruption. They in no way target the Venezuelan economy." The report also stated that the 2017 ban on dealing in Venezuelan government stocks and bonds allows exceptions for food and medicine, and that the 28 January 2019 PDVSA sanctions could worsen the situation, although "the crisis precedes them". The Washington Post stated that "the deprivation long predates recently imposed US sanctions". In 2011, the United States sanctioned Venezuela's state-owned oil company Petróleos de Venezuela . According to executives within the company as well as the Venezuelan government, the sanctions were mostly symbolic and had little effect (if any) on Venezuela's trade with the US since the company's sale of oil to the US and the operations of its US-based subsidiary Citgo were unaffected. On 9 March 2015, Barack Obama signed and issued an executive order declaring Venezuela a national security threat and ordered sanctions against Venezuelan officials. The sanctions did not affect Venezuela's oil company and trade relations with the US continued. In 2017, Trump's administration imposed additional economic sanctions on Venezuela. In 2018, the United Nations High Commissioner for Human Rights (OHCHR) documented that "information gathered indicates that the socioeconomic crisis had been unfolding for several years prior to the imposition of these sanctions". According to The Wall Street Journal , new 2019 sanctions, aimed at depriving the Maduro government of petroleum revenues. In 2019, former UN rapporteur Alfred de Zayas said that US sanctions on Venezuela were illegal as they constituted economic warfare and "could amount to 'crimes against humanity' under international law". His report, which he says was ignored by the UN, was criticized by the Latin America and Caribbean programme director for the Crisis Group for neglecting to mention the impact of a "difficult business environment on the country", which the director said "was a symptom of Chavismo and the socialist governments' failures", and that "Venezuela could not recover under current government policies even if the sanctions were lifted." Michelle Bachelet updated the situation in a 20 March oral report following the visit of a five-person delegation to Venezuela, saying that the social and economic crisis was dramatically deteriorating, the government had not acknowledged or addressed the extent of the crisis, and she was concerned that although the "pervasive and devastating economic and social crisis began before the imposition of the first economic sanctions", the sanctions could worsen the situation. In February 2019, Jorge Arreaza, Maduro's Minister for Foreign Affairs, said he was forming a coalition of diplomats who "believe the U.S. and others are violating the U.N. charter against non-interference in member states". During the announcement, he was surrounded by diplomats from 16 other countries, including Russia, China, Iran, North Korea, and Cuba. Arreaza said the cost to the Venezuelan economy of the US blockade was over $30 billion. Reporting on Arreaza's statements, the Associated Press said that Maduro was blocking aid, and "saying that Venezuelans are not beggars and that the move is part of a U.S.-led coup". During the COVID-19 pandemic , world leaders called for a suspension of economic sanctions, including against Venezuela and Iran, that have "increasingly become the pursuit of war by other means". The US responded by intensifying the sanctions against Venezuela. An October 2020 report published by the Washington Office on Latin America (WOLA) by Venezuelan economist Luis Oliveros found that "while Venezuela's economic crisis began before the first U.S. sectoral sanctions were imposed in 2017, these measures 'directly contributed to its deep decline, and to the further deterioration of the quality of life of Venezuelans' ". The report concluded that economic sanctions "have cost Venezuela's government as much as $31 billion since 2017" Alena Douhan , United Nations special rapporteur on the negative impact of unilateral coercive measures, was due to visit Venezuela in August 2020 to investigate the impact of international sanctions . Before her visit, 66 Venezuelan NGOs (including PROVEA ) asked Douhan in an open letter to consider the harmful impact of sanctions in the context of years of repression, corruption and economic mismanagement that predate the sanctions, and requested she meet independent press and civil society researchers. She arrived on 31 January, and was welcomed on arrival by a government minister and the Venezuelan ambassador to the UN. She declared on her preliminary findings as she left on 12 February: that sanctions against Venezuela have had a "devastating" noticeable impact in both the economy and the population. She said "the increasing number of unilateral sanctions imposed by United States, the European Union and other countries have exacerbated the economic and humanitarian calamities in Venezuela" but that Venezuela's economic decline "began in 2014 with the fall in oil prices" and that "mismanagement and corruption had also contributed." The government welcomed the report, while the opposition accused her of "playing into the hands of the regime" of Maduro. Douhan was harshly criticized by the Venezuelan civil society, and several non-governmental organizations pronounced themselves in social media with the hashtag " #Lacrisisfueprimero " (The crisis came first). On 11 August 2017, President Trump said that he is "not going to rule out a military option" to confront the autocratic government of Nicolás Maduro and the deepening crisis in Venezuela. Military Times said the unnamed aides told Trump it was not wise to even discuss a military solution due to the history of unpopular intervention in Latin America by the United States . Venezuela's Defense Minister Vladimir Padrino criticized Trump for the statement, calling it "an act of supreme extremism" and "an act of madness". The Venezuelan communications minister, Ernesto Villegas , said Trump's words amounted to "an unprecedented threat to national sovereignty". Representatives of the United States were in contact with dissident Venezuelan military officers during 2017 and 2018 but declined to collaborate with them or provide assistance to them. The opinion of other Latin American nations was split with respect to military intervention. Luis Almagro , the Secretary General of the Organization of American States , while visiting Colombia, did not rule out the potential benefit of the use of military force to intervene with the crisis. Canada, Colombia and Guyana, which are members of the Lima Group, refused to sign the organization's document rejecting military intervention in Venezuela. During the 2019 Venezuelan presidential crisis, allegations of potential United States military involvement began to circulate, with military intervention in Venezuela was already being executed by the governments of Cuba and Russia. According to professor Erick Langer of Georgetown University , while it was being discussed whether the United States would militarily intervene, "Cuba and Russia have already intervened". Hundreds or thousands of Cuban security forces have allegedly been operating in Venezuela while professor Robert Ellis of United States Army War College described the between several dozen and 400 Wagner Group mercenaries provided by Russia as the "palace guard of Nicolás Maduro". Kremlin spokesman Dmitry Peskov denied the deployment of Russian mercenaries, calling it "fake news". On 2 April 2019, the Russian Foreign Ministry rejected Trump's call to "get out" saying their 100 military servicemen now in Venezuela will support Maduro "for as long as needed". Throughout the crisis, humanitarian aid was provided to Venezuelans in need both within Venezuela and abroad. In October 2018, the USNS Comfort departed for an eleven-week operation in Latin America, with a primary mission being to assist countries who received Venezuelan refugees who fled the crisis in Venezuela . The main goal was to relieve health systems in Colombia, Ecuador, Peru and other nations which faced the arrival of thousands of Venezuelan migrants. At the end of January 2019, as the US prepared to bring aid across the border, the International Committee of the Red Cross warned the United States about the risk of delivering humanitarian aid without the approval of the government's security forces. The UN similarly warned the US about politicising the crisis and using aid as a pawn in the power struggle. Other humanitarian organisations also raised risks. On 23 February 2019, 14 trucks carrying 280 tons of humanitarian aid attempted to bring aid across the Simon Bolivar and Francisco de Paula Santander bridges from Colombia. There were clashes, with Venezuelan security forces reported to use tear gas attack in attempt to maintain a blockade of the border. Colombia said around 285 people were injured and at least two trucks set on fire. CNN reported that the Venezuela government accused Guaidó supporters of burning the trucks and noted that "While a CNN team saw incendiary devices from police on the Venezuelan side of the border ignite the trucks, the network's journalists are unsure if the trucks were burned on purpose." In March, The New York Times reported that footage showed that it was anti-Maduro protestors rather than Venezuelan security forces who were responsible for the burning trucks. The New York Times reported that the trucks had been set on fire by anti-Maduro protester who threw a Molotov cocktail that hit one of the trucks. Colombian foreign minister Carlos Holmes Trujillo rejected the claims by The New York Times that the Colombian government manipulated the video of the burning of the aid truck, insisting that Nicolás Maduro was responsible. Responding when asked about the claims in a BBC interview, Juan Guaidó stressed that its findings suggested only a possible theory, that it was the newspaper's point of view and that a total of three trucks were burned, while the footage focused on one. Journalist Karla Salcedo Flores denounced state-run Telesur for plagiarism and the manipulation of her photos for propaganda purposes after the network claimed protesters poured gasoline on the trucks. Agence France-Presse published an investigation disproving Telesur's claims with the photos. Bellingcat reported that since the open source evidence examined for its investigation does not show the moment of ignition, it is not possible to make a definitive determination regarding the cause of the fire. Franceso Rocca, president of the International Federation of Red Cross and Red Crescent Societies , announced on 29 March 2019 that the Red Cross was preparing to bring humanitarian aid to the country to help ease both the chronic hunger and the medical crisis. The Guardian reported that Maduro had "long denied the existence of a humanitarian crisis, and on 23 February blocked an effort led by Guaidó to bring aid into the country", and that the Red Cross had "brokered a deal" between the Maduro and Guaidó administrations "indicating a seldom-seen middle ground between the two men". The Red Cross aid shipments were expected to begin within a few weeks, and the first shipment would help about 650,000 people; simultaneously, a leaked UN report estimated that seven million Venezuelans were likely in need of humanitarian assistance. During what The Wall Street Journal called "Latin America's worst humanitarian crisis ever", the "operation would rival Red Cross relief efforts in war-torn Syria, signaling the depth of Venezuela's crisis." Rocca said the efforts would focus first on hospitals, including state-run facilities, and said the Red Cross was open to the possibility of delivering aid products stored on the Venezuelan borders with Colombia and Brazil. He warned that the Red Cross would not accept any political interference, and said the effort must be "independent, neutral, impartial and unhindered". Maduro and Arreaza met with representative of Red Cross International on 9 April to discuss the aid effort. The Wall Street Journal said that the acceptance of humanitarian shipments by Maduro was his first acknowledgement that Venezuela is "suffering from an economic collapse", adding that "until a few days ago, the government maintained there was no crisis and it didn't need outside help". Guaidó said the acceptance of humanitarian aid was the "result of our pressure and insistence", and called on Venezuelans to "stay vigilant to make sure incoming aid is not diverted for 'corrupt' purposes". The first Red Cross delivery of supplies for hospitals arrived on 16 April, offering an encouraging sign that the Maduro administration would allow more aid to enter. Quoting Tamara Taraciuk—an expert at Human Rights Watch on Venezuela—who called the situation "a completely man-made crisis", The New York Times said the aid effort in Venezuela presented challenges regarding how to deliver aid in an "unprecedented political, economic and humanitarian crisis" that was "caused largely by the policies of a government intent on staying in power, rather than war or natural disaster". Armed pro-government paramilitaries fired weapons to disrupt the first Red Cross delivery, and officials associated with Maduro's party told the Red Cross to leave. An April 2021 report by the inspector general at United States Agency for International Development found that the Trump administration had politicized the early 2019 humanitarian aid package and was motivated by regime change in Venezuela more so than ameliorating the humanitarian situation there. The European Union, the Lima Group, the United States and other countries have applied individual sanctions against government officials and members of both the military and security forces as a response to human rights violations, corruption, degradation in the rule of law and repression of democracy . The United States would later extend its sanctions to the petroleum sector. Economists have stated that shortages and high inflation in Venezuela began before US sanctions were directed towards the country. The Wall Street Journal said that economists place the blame for Venezuela's economy shrinking by half on "Maduro's policies, including widespread nationalizations, out-of-control spending that sparked inflation, price controls that led to shortages, and widespread graft and mismanagement." The Venezuelan government has stated that the United States is responsible for its economic collapse. The HRW/Johns Hopkins report noted that most sanctions are "limited to canceling visas and freezing assets of key officials implicated in abuses and corruption. They in no way target the Venezuelan economy." The report also stated that the 2017 ban on dealing in Venezuelan government stocks and bonds allows exceptions for food and medicine, and that the 28 January 2019 PDVSA sanctions could worsen the situation, although "the crisis precedes them". The Washington Post stated that "the deprivation long predates recently imposed US sanctions". In 2011, the United States sanctioned Venezuela's state-owned oil company Petróleos de Venezuela . According to executives within the company as well as the Venezuelan government, the sanctions were mostly symbolic and had little effect (if any) on Venezuela's trade with the US since the company's sale of oil to the US and the operations of its US-based subsidiary Citgo were unaffected. On 9 March 2015, Barack Obama signed and issued an executive order declaring Venezuela a national security threat and ordered sanctions against Venezuelan officials. The sanctions did not affect Venezuela's oil company and trade relations with the US continued. In 2017, Trump's administration imposed additional economic sanctions on Venezuela. In 2018, the United Nations High Commissioner for Human Rights (OHCHR) documented that "information gathered indicates that the socioeconomic crisis had been unfolding for several years prior to the imposition of these sanctions". According to The Wall Street Journal , new 2019 sanctions, aimed at depriving the Maduro government of petroleum revenues. In 2019, former UN rapporteur Alfred de Zayas said that US sanctions on Venezuela were illegal as they constituted economic warfare and "could amount to 'crimes against humanity' under international law". His report, which he says was ignored by the UN, was criticized by the Latin America and Caribbean programme director for the Crisis Group for neglecting to mention the impact of a "difficult business environment on the country", which the director said "was a symptom of Chavismo and the socialist governments' failures", and that "Venezuela could not recover under current government policies even if the sanctions were lifted." Michelle Bachelet updated the situation in a 20 March oral report following the visit of a five-person delegation to Venezuela, saying that the social and economic crisis was dramatically deteriorating, the government had not acknowledged or addressed the extent of the crisis, and she was concerned that although the "pervasive and devastating economic and social crisis began before the imposition of the first economic sanctions", the sanctions could worsen the situation. In February 2019, Jorge Arreaza, Maduro's Minister for Foreign Affairs, said he was forming a coalition of diplomats who "believe the U.S. and others are violating the U.N. charter against non-interference in member states". During the announcement, he was surrounded by diplomats from 16 other countries, including Russia, China, Iran, North Korea, and Cuba. Arreaza said the cost to the Venezuelan economy of the US blockade was over $30 billion. Reporting on Arreaza's statements, the Associated Press said that Maduro was blocking aid, and "saying that Venezuelans are not beggars and that the move is part of a U.S.-led coup". During the COVID-19 pandemic , world leaders called for a suspension of economic sanctions, including against Venezuela and Iran, that have "increasingly become the pursuit of war by other means". The US responded by intensifying the sanctions against Venezuela. An October 2020 report published by the Washington Office on Latin America (WOLA) by Venezuelan economist Luis Oliveros found that "while Venezuela's economic crisis began before the first U.S. sectoral sanctions were imposed in 2017, these measures 'directly contributed to its deep decline, and to the further deterioration of the quality of life of Venezuelans' ". The report concluded that economic sanctions "have cost Venezuela's government as much as $31 billion since 2017" Alena Douhan , United Nations special rapporteur on the negative impact of unilateral coercive measures, was due to visit Venezuela in August 2020 to investigate the impact of international sanctions . Before her visit, 66 Venezuelan NGOs (including PROVEA ) asked Douhan in an open letter to consider the harmful impact of sanctions in the context of years of repression, corruption and economic mismanagement that predate the sanctions, and requested she meet independent press and civil society researchers. She arrived on 31 January, and was welcomed on arrival by a government minister and the Venezuelan ambassador to the UN. She declared on her preliminary findings as she left on 12 February: that sanctions against Venezuela have had a "devastating" noticeable impact in both the economy and the population. She said "the increasing number of unilateral sanctions imposed by United States, the European Union and other countries have exacerbated the economic and humanitarian calamities in Venezuela" but that Venezuela's economic decline "began in 2014 with the fall in oil prices" and that "mismanagement and corruption had also contributed." The government welcomed the report, while the opposition accused her of "playing into the hands of the regime" of Maduro. Douhan was harshly criticized by the Venezuelan civil society, and several non-governmental organizations pronounced themselves in social media with the hashtag " #Lacrisisfueprimero " (The crisis came first). On 11 August 2017, President Trump said that he is "not going to rule out a military option" to confront the autocratic government of Nicolás Maduro and the deepening crisis in Venezuela. Military Times said the unnamed aides told Trump it was not wise to even discuss a military solution due to the history of unpopular intervention in Latin America by the United States . Venezuela's Defense Minister Vladimir Padrino criticized Trump for the statement, calling it "an act of supreme extremism" and "an act of madness". The Venezuelan communications minister, Ernesto Villegas , said Trump's words amounted to "an unprecedented threat to national sovereignty". Representatives of the United States were in contact with dissident Venezuelan military officers during 2017 and 2018 but declined to collaborate with them or provide assistance to them. The opinion of other Latin American nations was split with respect to military intervention. Luis Almagro , the Secretary General of the Organization of American States , while visiting Colombia, did not rule out the potential benefit of the use of military force to intervene with the crisis. Canada, Colombia and Guyana, which are members of the Lima Group, refused to sign the organization's document rejecting military intervention in Venezuela. During the 2019 Venezuelan presidential crisis, allegations of potential United States military involvement began to circulate, with military intervention in Venezuela was already being executed by the governments of Cuba and Russia. According to professor Erick Langer of Georgetown University , while it was being discussed whether the United States would militarily intervene, "Cuba and Russia have already intervened". Hundreds or thousands of Cuban security forces have allegedly been operating in Venezuela while professor Robert Ellis of United States Army War College described the between several dozen and 400 Wagner Group mercenaries provided by Russia as the "palace guard of Nicolás Maduro". Kremlin spokesman Dmitry Peskov denied the deployment of Russian mercenaries, calling it "fake news". On 2 April 2019, the Russian Foreign Ministry rejected Trump's call to "get out" saying their 100 military servicemen now in Venezuela will support Maduro "for as long as needed". Throughout the crisis, humanitarian aid was provided to Venezuelans in need both within Venezuela and abroad. In October 2018, the USNS Comfort departed for an eleven-week operation in Latin America, with a primary mission being to assist countries who received Venezuelan refugees who fled the crisis in Venezuela . The main goal was to relieve health systems in Colombia, Ecuador, Peru and other nations which faced the arrival of thousands of Venezuelan migrants. At the end of January 2019, as the US prepared to bring aid across the border, the International Committee of the Red Cross warned the United States about the risk of delivering humanitarian aid without the approval of the government's security forces. The UN similarly warned the US about politicising the crisis and using aid as a pawn in the power struggle. Other humanitarian organisations also raised risks. On 23 February 2019, 14 trucks carrying 280 tons of humanitarian aid attempted to bring aid across the Simon Bolivar and Francisco de Paula Santander bridges from Colombia. There were clashes, with Venezuelan security forces reported to use tear gas attack in attempt to maintain a blockade of the border. Colombia said around 285 people were injured and at least two trucks set on fire. CNN reported that the Venezuela government accused Guaidó supporters of burning the trucks and noted that "While a CNN team saw incendiary devices from police on the Venezuelan side of the border ignite the trucks, the network's journalists are unsure if the trucks were burned on purpose." In March, The New York Times reported that footage showed that it was anti-Maduro protestors rather than Venezuelan security forces who were responsible for the burning trucks. The New York Times reported that the trucks had been set on fire by anti-Maduro protester who threw a Molotov cocktail that hit one of the trucks. Colombian foreign minister Carlos Holmes Trujillo rejected the claims by The New York Times that the Colombian government manipulated the video of the burning of the aid truck, insisting that Nicolás Maduro was responsible. Responding when asked about the claims in a BBC interview, Juan Guaidó stressed that its findings suggested only a possible theory, that it was the newspaper's point of view and that a total of three trucks were burned, while the footage focused on one. Journalist Karla Salcedo Flores denounced state-run Telesur for plagiarism and the manipulation of her photos for propaganda purposes after the network claimed protesters poured gasoline on the trucks. Agence France-Presse published an investigation disproving Telesur's claims with the photos. Bellingcat reported that since the open source evidence examined for its investigation does not show the moment of ignition, it is not possible to make a definitive determination regarding the cause of the fire. Franceso Rocca, president of the International Federation of Red Cross and Red Crescent Societies , announced on 29 March 2019 that the Red Cross was preparing to bring humanitarian aid to the country to help ease both the chronic hunger and the medical crisis. The Guardian reported that Maduro had "long denied the existence of a humanitarian crisis, and on 23 February blocked an effort led by Guaidó to bring aid into the country", and that the Red Cross had "brokered a deal" between the Maduro and Guaidó administrations "indicating a seldom-seen middle ground between the two men". The Red Cross aid shipments were expected to begin within a few weeks, and the first shipment would help about 650,000 people; simultaneously, a leaked UN report estimated that seven million Venezuelans were likely in need of humanitarian assistance. During what The Wall Street Journal called "Latin America's worst humanitarian crisis ever", the "operation would rival Red Cross relief efforts in war-torn Syria, signaling the depth of Venezuela's crisis." Rocca said the efforts would focus first on hospitals, including state-run facilities, and said the Red Cross was open to the possibility of delivering aid products stored on the Venezuelan borders with Colombia and Brazil. He warned that the Red Cross would not accept any political interference, and said the effort must be "independent, neutral, impartial and unhindered". Maduro and Arreaza met with representative of Red Cross International on 9 April to discuss the aid effort. The Wall Street Journal said that the acceptance of humanitarian shipments by Maduro was his first acknowledgement that Venezuela is "suffering from an economic collapse", adding that "until a few days ago, the government maintained there was no crisis and it didn't need outside help". Guaidó said the acceptance of humanitarian aid was the "result of our pressure and insistence", and called on Venezuelans to "stay vigilant to make sure incoming aid is not diverted for 'corrupt' purposes". The first Red Cross delivery of supplies for hospitals arrived on 16 April, offering an encouraging sign that the Maduro administration would allow more aid to enter. Quoting Tamara Taraciuk—an expert at Human Rights Watch on Venezuela—who called the situation "a completely man-made crisis", The New York Times said the aid effort in Venezuela presented challenges regarding how to deliver aid in an "unprecedented political, economic and humanitarian crisis" that was "caused largely by the policies of a government intent on staying in power, rather than war or natural disaster". Armed pro-government paramilitaries fired weapons to disrupt the first Red Cross delivery, and officials associated with Maduro's party told the Red Cross to leave. An April 2021 report by the inspector general at United States Agency for International Development found that the Trump administration had politicized the early 2019 humanitarian aid package and was motivated by regime change in Venezuela more so than ameliorating the humanitarian situation there.

Wiki

Chikungunya

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

List of diseases spread by arthropods

Arthropods are common vectors of disease . A vector is an organism which spreads disease-causing parasites or pathogens from one host to another. Invertebrates spread bacterial, viral and protozoan pathogens by two main mechanisms. Either via their bite, as in the case of malaria spread by mosquitoes, or via their faeces, as in the case of Chagas' Disease spread by Triatoma bugs or epidemic typhus spread by human body lice. Many invertebrates are responsible for transmitting diseases. Mosquitoes are perhaps the best known invertebrate vector and transmit a wide range of tropical diseases including malaria, dengue fever and yellow fever. Another large group of vectors are flies. Sandfly species transmit the disease leishmaniasis, by acting as vectors for protozoan Leishmania species, and tsetse flies transmit protozoan trypansomes ( Trypanosoma brucei gambiense and Trypansoma brucei rhodesiense ) which cause African Trypanosomiasis (sleeping sickness). Ticks and lice form another large group of invertebrate vectors. The bacterium Borrelia burgdorferi , which causes Lyme Disease, is transmitted by ticks and members of the bacterial genus Rickettsia are transmitted by lice. For example, the human body louse transmits the bacterium Rickettsia prowazekii which causes epidemic typhus. Although invertebrate-transmitted diseases pose a particular threat on the continents of Africa, Asia and South America, there is one way of controlling invertebrate-borne diseases, which is by controlling the invertebrate vector. For example, one way of controlling malaria is to control the mosquito vector through the use of mosquito nets, which prevent mosquitoes from coming into contact with humans.

Wiki

Chikungunya

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

List of infectious diseases

This is a list of infectious diseases arranged by name, along with the infectious agents that cause them, the vaccines that can prevent or cure them when they exist and their current status. Some on the list are vaccine-preventable diseases .Blood infection: Fever, chills, vomiting, confusion Urinary tract infection: bloody urine, cloudy urine Pneumonia: Fever, chills, coughing high fever that lasts 4–6 days pharyngitis (sore throat) conjunctivitis (inflamed eyes, usually without pus formation like pink eye) enlargement of the lymph nodes of the neck headache, malaise, and weakness Incubation period of 5–9 days Hemolymphatic phase: Fever, lymphadenopathy Neurological phase: Sleep disorders, neurological symptoms, psychiatric symptoms Suramin by injection is used for T. b. rhodesiense Symptoms of vaginal candidiasis are vaginal itching or soreness, pain during sexual intercourse In men, painful or burning sensation when urinating Isolation of C. diphtheriae culture Histopathologic diagnosis Toxin demonstration In vivo tests (guinea pig inoculation) In vitro test: Elek's gel precipitation test, PCR, ELISA, ICA Clinical criteria URT illness with sore throat Low-grade fever An adherent, dense, grey pseudomembrane covering the posterior aspect of the pharynx Pneumonia: fever, lung consolidation, pleural effusion, tachypnea, tachycardia, or hypotension Meningitis: fever, confusion, hypotension, headache, nuchal rigidity, or changing mental status Bacteremia: fever, murmur, evidence of an embolic event, hypotension, phlebitis, tachycardia, tachypnea, splenomegaly, or evidence of heart failure Skin and soft tissue infection, osteomyelitis, septic arthritis, or discitis: fever, cellulitis, arthritis, arthralgia, localized pain, decubitus ulcer, vascular insufficiency of the lower extremity, back pain, wound infection, or neurologic dysfunction Urinary tract infection or pelvic abscess: fever, flank pain, pelvic pain, or abdominal pain fever severe headache muscle aches ( myalgia ) chills and shaking, similar to the symptoms of influenza nausea vomiting loss of appetite unintentional weight loss abdominal pain cough Skin lesion consistent with leprosy and with definite sensory loss. Positive skin smears. Neurological infection Headache, lethargy, confusion, seizures, sudden onset of neurological deficit Cardiac conditions In recorded cases, it has caused damage to heart valves whether natural or prosthetic Lymphocutaneous disease Ocular disease Disseminated nocardiosis Fever, moderate or very high can be seen

Wiki

Chikungunya

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

Rubella

Rubella , also known as German measles or three-day measles , is an infection caused by the rubella virus . This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is sometimes itchy and is not as bright as that of measles . Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. Joint pain is common in adults. Complications may include bleeding problems, testicular swelling , encephalitis, and inflammation of nerves . Infection during early pregnancy may result in a miscarriage or a child born with congenital rubella syndrome (CRS). Symptoms of CRS manifest as problems with the eyes such as cataracts , deafness , as well as affecting the heart and brain. Problems are rare after the 20th week of pregnancy. Rubella is usually spread from one person to the next through the air via coughs of people who are infected. People are infectious during the week before and after the appearance of the rash. Babies with CRS may spread the virus for more than a year. Only humans are infected. Insects do not spread the disease. Once recovered, people are immune to future infections. Testing is available that can verify immunity. Diagnosis is confirmed by finding the virus in the blood, throat, or urine. Testing the blood for antibodies may also be useful. Rubella is preventable with the rubella vaccine with a single dose being more than 95% effective. Often it is given in combination with the measles vaccine and mumps vaccine , known as the MMR vaccine . When some, but less than 80%, of a population is vaccinated, more women may reach childbearing age without developing immunity by infection or vaccination, thus possibly raising CRS rates. Once infected there is no specific treatment. Rubella is a common infection in many areas of the world. Each year about 100,000 cases of congenital rubella syndrome occur. Rates of disease have decreased in many areas as a result of vaccination. There are ongoing efforts to eliminate the disease globally. In April 2015, the World Health Organization declared the Americas free of rubella transmission. The name "rubella" is from Latin and means little red . It was first described as a separate disease by German physicians in 1814, resulting in the name "German measles". Rubella has symptoms similar to those of flu. However, the primary symptom of rubella virus infection is the appearance of a rash (exanthem) on the face which spreads to the trunk and limbs and usually fades after three days, which is why it is often referred to as three-day measles. The facial rash usually clears as it spreads to other parts of the body. Other symptoms include low-grade fever, swollen glands (sub-occipital and posterior cervical lymphadenopathy ), joint pains , headache , and conjunctivitis . The swollen glands or lymph nodes can persist for up to a week and the fever rarely rises above 38 °C (100.4 °F). The rash of rubella is typically pink or light red. The rash causes itching and often lasts for about three days. The rash disappears after a few days with no staining or peeling of the skin. When the rash clears up, the skin might shed in very small flakes where the rash covered it. Forchheimer spots occur in 20% of cases and is characterized by small, red papules on the area of the soft palate . Rubella can affect anyone of any age. Adult females are particularly prone to arthritis and joint pains. In children, rubella normally causes symptoms that last two days and include: Rash begins on the face which spreads to the rest of the body. Low fever of less than 38.3 °C (100.9 °F) . Posterior cervical lymphadenopathy. In older children and adults, additional symptoms may be present, including [ citation needed ] Swollen glands Coryza (cold-like symptoms) Aching joints (especially in young females) Severe complications of rubella include: Coryza in rubella may convert to pneumonia , either direct viral pneumonia or secondary bacterial pneumonia , and bronchitis (either viral bronchitis or secondary bacterial bronchitis). Rubella can cause congenital rubella syndrome in the newborn, this being the most severe sequela of rubella. The syndrome (CRS) follows intrauterine infection by the rubella virus and comprises cardiac, cerebral, ophthalmic, and auditory defects. It may also cause prematurity, low birth weight, neonatal thrombocytopenia, anemia, and hepatitis. The risk of major defects in organogenesis is highest for infection in the first trimester . CRS is the main reason a vaccine for rubella was developed. 80–90% of mothers who contract rubella within the critical first trimester have either a miscarriage or a stillborn baby. If the fetus survives the infection, it can be born with severe heart disorders ( patent ductus arteriosus being the most common), blindness, deafness, or other life-threatening organ disorders. The skin manifestations are called "blueberry muffin lesions". For these reasons, rubella is included in the TORCH complex of perinatal infections. About 100,000 cases of this condition occur each year. Rubella can cause congenital rubella syndrome in the newborn, this being the most severe sequela of rubella. The syndrome (CRS) follows intrauterine infection by the rubella virus and comprises cardiac, cerebral, ophthalmic, and auditory defects. It may also cause prematurity, low birth weight, neonatal thrombocytopenia, anemia, and hepatitis. The risk of major defects in organogenesis is highest for infection in the first trimester . CRS is the main reason a vaccine for rubella was developed. 80–90% of mothers who contract rubella within the critical first trimester have either a miscarriage or a stillborn baby. If the fetus survives the infection, it can be born with severe heart disorders ( patent ductus arteriosus being the most common), blindness, deafness, or other life-threatening organ disorders. The skin manifestations are called "blueberry muffin lesions". For these reasons, rubella is included in the TORCH complex of perinatal infections. About 100,000 cases of this condition occur each year. The disease is caused by the rubella virus, in the genus Rubivirus from the family Matonaviridae, that is enveloped and has a single-stranded RNA genome. The virus is transmitted by the respiratory route and replicates in the nasopharynx and lymph nodes . The virus is found in the blood 5 to 7 days after infection and spreads throughout the body. The virus has teratogenic properties and is capable of crossing the placenta and infecting the fetus where it stops cells from developing or destroys them. During this incubation period, the patient is contagious typically for about one week before he/she develops a rash and for about one week thereafter. Increased susceptibility to infection might be inherited as there is some indication that HLA-A1 or factors surrounding A1 on extended haplotypes are involved in virus infection or non-resolution of the disease. Rubella virus specific IgM antibodies are present in people recently infected by rubella virus, but these antibodies can persist for over a year, and a positive test result needs to be interpreted with caution. The presence of these antibodies along with, or a short time after, the characteristic rash confirms the diagnosis. Rubella infections are prevented by active immunization programs using live attenuated virus vaccines . Two live attenuated virus vaccines, RA 27/3 and Cendehill strains, were effective in the prevention of adult disease. However, their use in prepubertal females did not produce a significant fall in the overall incidence rate of CRS in the UK. Reductions were only achieved by immunisation of all children. The vaccine is now usually given as part of the MMR vaccine . The WHO recommends the first dose be given at 12 to 18 months of age with a second dose at 36 months. Pregnant women are usually tested for immunity to rubella early on. Women found to be susceptible are not vaccinated until after the baby is born because the vaccine contains live virus. The immunisation program has been quite successful. Cuba declared the disease eliminated in the 1990s, and in 2004 the Centers for Disease Control and Prevention announced that both the congenital and acquired forms of rubella had been eliminated from the United States . The World Health Organization declared Australia rubella free in October 2018. Screening for rubella susceptibility by history of vaccination or by serology is recommended in the United States for all women of childbearing age at their first preconception counseling visit to reduce incidence of congenital rubella syndrome (CRS). It is recommended that all susceptible non-pregnant women of childbearing age should be offered rubella vaccination. Due to concerns about possible teratogenicity, use of MMR vaccine is not recommended during pregnancy. Instead, susceptible pregnant women should be vaccinated as soon as possible in the postpartum period . In susceptible people passive immunization , in the form of polyclonal immunoglobulins , appears effective up to the fifth day post-exposure. There is no specific treatment for rubella; however, management is a matter of responding to symptoms to diminish discomfort. Treatment of newborn babies is focused on management of the complications. Congenital heart defects and cataracts can be corrected by direct surgery. Management for ocular congenital rubella syndrome (CRS) is similar to that for age-related macular degeneration , including counseling, regular monitoring, and the provision of low vision devices, if required. Rubella infection of children and adults is usually mild, self-limiting, and often asymptomatic. The prognosis in children born with CRS is poor. Rubella occurs worldwide. The virus tends to peak during the spring in countries with temperate climates. Before the vaccine against rubella was introduced in 1969, widespread outbreaks usually occurred every 6–9 years in the United States and 3–5 years in Europe , mostly affecting children in the 5–9 year old age group. Since the introduction of vaccine, occurrences have become rare in those countries with high uptake rates. [ citation needed ] Vaccination has interrupted the transmission of rubella in the Americas : no endemic case has been observed since February 2009. Vaccination is still strongly recommended as the virus could be reintroduced from other continents should vaccination rates in the Americas drop. During the epidemic in the US between 1962 and 1965 , rubella virus infections during pregnancy were estimated to have caused 30,000 stillbirths and 20,000 children to be born impaired or disabled as a result of CRS. Universal immunisation producing a high level of herd immunity is important in the control of epidemics of rubella. In the UK , there remains a large population of men susceptible to rubella who have not been vaccinated. Outbreaks of rubella occurred amongst many young men in the UK in 1993 and in 1996 the infection was transmitted to pregnant women, many of whom were immigrants and were susceptible. Outbreaks still arise, usually in developing countries where the vaccine is not as accessible. The complications encountered in pregnancy from rubella infection (miscarriage, fetal death, congenital rubella syndrome) are more common in Africa and Southeast Asia at a rate of 121 per 100,000 live births compared to 2 per 100,000 live births in the Americas and Europe. In Japan , 15,000 cases of rubella and 43 cases of congenital rubella syndrome were reported to the National Epidemiological Surveillance of Infectious Diseases between October 15, 2012, and March 2, 2014, during the 2012–13 rubella outbreak in Japan. They mainly occurred in men aged 31–51 and young adults aged 24–34. Rubella was first described in the mid-eighteenth century. German physician and chemist, Friedrich Hoffmann , made the first clinical description of rubella in 1740, which was confirmed by de Bergen in 1752 and Orlow in 1758. In 1814, George de Maton first suggested that it be considered a disease distinct from both measles and scarlet fever . All these physicians were German, and the disease was known as Rötheln (contemporary German Röteln ). ( Rötlich means "reddish" or "pink" in German.) The fact that three Germans described it led to the common name of "German measles." Henry Veale, an English Royal Artillery surgeon, described an outbreak in India. He coined the name "rubella" (from the Latin word, meaning "little red") in 1866. It was formally recognised as an individual entity in 1881, at the International Congress of Medicine in London . In 1914, Alfred Fabian Hess theorised that rubella was caused by a virus, based on work with monkeys. In 1938, Hiro and Tosaka confirmed this by passing the disease to children using filtered nasal washings from acute cases. In 1940, there was a widespread epidemic of rubella in Australia . Subsequently, ophthalmologist Norman McAllister Gregg found 78 cases of congenital cataracts in infants and 68 of them were born to mothers who had caught rubella in early pregnancy. Gregg published an account, Congenital Cataract Following German Measles in the Mother , in 1941. He described a variety of problems now known as congenital rubella syndrome (CRS) and noticed that the earlier the mother was infected, the worse the damage was. Since no vaccine was yet available, some popular magazines promoted the idea of "German measles parties" for infected children to spread the disease to other children (especially girls) to immunize them for life and protect them from later catching the disease when pregnant. The virus was isolated in tissue culture in 1962 by two separate groups led by physicians Paul Douglas Parkman and Thomas Huckle Weller . There was a pandemic of rubella between 1962 and 1965, starting in Europe and spreading to the United States. In the years 1964–65, the United States had an estimated 12.5 million rubella cases ( 1964–1965 rubella epidemic ). This led to 11,000 miscarriages or therapeutic abortions and 20,000 cases of congenital rubella syndrome. Of these, 2,100 died as neonates, 12,000 were deaf, 3,580 were blind, and 1,800 were intellectually disabled. In New York alone, CRS affected 1% of all births. In 1967, the molecular structure of rubella was observed under electron microscopy using antigen-antibody complexes by Jennifer M. Best, June Almeida , J E Banatvala and A P Waterson. In 1969, a live attenuated virus vaccine was licensed. In the early 1970s, a triple vaccine containing attenuated measles, mumps and rubella (MMR) viruses was introduced. By 2006, confirmed cases in the Americas had dropped below 3000 a year. However, a 2007 outbreak in Argentina , Brazil , and Chile pushed the cases to 13,000 that year. On January 22, 2014, the World Health Organization (WHO) and the Pan American Health Organization declared and certified Colombia free of rubella and became the first Latin American country to eliminate the disease within its borders. On April 29, 2015, the Americas became the first WHO region to officially eradicate the disease. The last non-imported cases occurred in 2009 in Argentina and Brazil. The Pan American Health Organization director remarked, "The fight against rubella has taken more than 15 years, but it has paid off with what I believe will be one of the most important pan-American public health achievements of the 21st Century." The declaration was made after 165 million health records and genetically confirming that all recent cases were caused by known imported strains of the virus. Rubella is still common in some regions of the world and Susan E. Reef, team lead for rubella at the CDC's global immunization division, who joined in the announcement, said there was no chance it would be eradicated worldwide before 2020. Rubella is the third disease to be eliminated from the Western Hemisphere with vaccination after smallpox and polio . On January 22, 2014, the World Health Organization (WHO) and the Pan American Health Organization declared and certified Colombia free of rubella and became the first Latin American country to eliminate the disease within its borders. On April 29, 2015, the Americas became the first WHO region to officially eradicate the disease. The last non-imported cases occurred in 2009 in Argentina and Brazil. The Pan American Health Organization director remarked, "The fight against rubella has taken more than 15 years, but it has paid off with what I believe will be one of the most important pan-American public health achievements of the 21st Century." The declaration was made after 165 million health records and genetically confirming that all recent cases were caused by known imported strains of the virus. Rubella is still common in some regions of the world and Susan E. Reef, team lead for rubella at the CDC's global immunization division, who joined in the announcement, said there was no chance it would be eradicated worldwide before 2020. Rubella is the third disease to be eliminated from the Western Hemisphere with vaccination after smallpox and polio . From "rubrum" the Latin for "red", rubella means "reddish and small". "German" measles derives from "germanus" which means "similar" in this context. The name rubella is sometimes confused with rubeola , an alternative name for measles in English-speaking countries; the diseases are unrelated. In some other European languages, like Spanish , rubella and rubeola are synonyms, and rubeola is not an alternative name for measles. Thus, in Spanish, rubeola refers to rubella and sarampión refers to measles.

Wiki

Cholera

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

Cholera

Cholera ( / ˈ k ɒ l ər ə / ) is an infection of the small intestine by some strains of the bacterium Vibrio cholerae . Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Vomiting and muscle cramps may also occur. Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance . This may result in sunken eyes , cold skin, decreased skin elasticity, and wrinkling of the hands and feet. Dehydration can cause the skin to turn bluish . Symptoms start two hours to five days after exposure. Cholera is caused by a number of types of Vibrio cholerae , with some types producing more severe disease than others. It is spread mostly by unsafe water and unsafe food that has been contaminated with human feces containing the bacteria. Undercooked shellfish is a common source. Humans are the only known host for the bacteria . Risk factors for the disease include poor sanitation , insufficient clean drinking water , and poverty . Cholera can be diagnosed by a stool test , or a rapid dipstick test , although the dipstick test is less accurate. Prevention methods against cholera include improved sanitation and access to clean water . Cholera vaccines that are given by mouth provide reasonable protection for about six months, and confer the added benefit of protecting against another type of diarrhea caused by E. coli . In 2017 the US Food and Drug Administration (FDA) approved a single-dose, live, oral cholera vaccine called Vaxchora for adults aged 18–64 who are travelling to an area of active cholera transmission. It offers limited protection to young children. People who survive an episode of cholera have long-lasting immunity for at least three years (the period tested). The primary treatment for affected individuals is oral rehydration salts (ORS), the replacement of fluids and electrolytes by using slightly sweet and salty solutions. Rice-based solutions are preferred. In children, zinc supplementation has also been found to improve outcomes. In severe cases, intravenous fluids , such as Ringer's lactate , may be required, and antibiotics may be beneficial. The choice of antibiotic is aided by antibiotic sensitivity testing . Cholera continues to affect an estimated 3–5 million people worldwide and causes 28,800–130,000 deaths a year. To date, seven cholera pandemics have occurred in the developing world, with the most recent beginning in 1961, and continuing today. The illness is rare in high-income countries , and affects children most severely. Cholera occurs as both outbreaks and chronically in certain areas . Areas with an ongoing risk of disease include Africa and Southeast Asia . The risk of death among those affected is usually less than 5%, given improved treatment, but may be as high as 50% without such access to treatment. Descriptions of cholera are found as early as the 5th century BC in Sanskrit . In Europe, cholera was a term initially used to describe any kind of gastroenteritis, and was not used for this disease until the early 19th century. The study of cholera in England by John Snow between 1849 and 1854 led to significant advances in the field of epidemiology because of his insights about transmission via contaminated water, and a map of the same was the first recorded incidence of epidemiological tracking. The primary symptoms of cholera are profuse diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, half a day to five days after ingestion of the bacteria. The diarrhea is frequently described as "rice water" in nature and may have a fishy odor. An untreated person with cholera may produce 10 to 20 litres (3 to 5 US gal) of diarrhea a day. Severe cholera, without treatment, kills about half of affected individuals. If the severe diarrhea is not treated, it can result in life-threatening dehydration and electrolyte imbalances. Estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100. Cholera has been nicknamed the "blue death" because a person's skin may turn bluish-gray from extreme loss of fluids. Fever is rare and should raise suspicion for secondary infection. Patients can be lethargic and might have sunken eyes, dry mouth, cold clammy skin, or wrinkled hands and feet. Kussmaul breathing , a deep and labored breathing pattern, can occur because of acidosis from stool bicarbonate losses and lactic acidosis associated with poor perfusion . Blood pressure drops due to dehydration, peripheral pulse is rapid and thready, and urine output decreases with time. Muscle cramping and weakness, altered consciousness, seizures , or even coma due to electrolyte imbalances are common, especially in children. Cholera bacteria have been found in shellfish and plankton . Transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation . Most cholera cases in developed countries are a result of transmission by food, while in developing countries it is more often water. Food transmission can occur when people harvest seafood such as oysters in waters infected with sewage , as Vibrio cholerae accumulates in planktonic crustaceans and the oysters eat the zooplankton . People infected with cholera often have diarrhea, and disease transmission may occur if this highly liquid stool, colloquially referred to as "rice-water", contaminates water used by others. A single diarrheal event can cause a one-million fold increase in numbers of V. cholerae in the environment. The source of the contamination is typically other people with cholera when their untreated diarrheal discharge is allowed to get into waterways, groundwater or drinking water supplies. Drinking any contaminated water and eating any foods washed in the water, as well as shellfish living in the affected waterway , can cause a person to contract an infection. Cholera is rarely spread directly from person to person . [note 1] V. cholerae also exists outside the human body in natural water sources, either by itself or through interacting with phytoplankton , zooplankton , or biotic and abiotic detritus. Drinking such water can also result in the disease, even without prior contamination through fecal matter. Selective pressures exist however in the aquatic environment that may reduce the virulence of V. cholerae . Specifically, animal models indicate that the transcriptional profile of the pathogen changes as it prepares to enter an aquatic environment. This transcriptional change results in a loss of ability of V. cholerae to be cultured on standard media, a phenotype referred to as ' viable but non-culturable ' (VBNC) or more conservatively ' active but non-culturable ' (ABNC). One study indicates that the culturability of V. cholerae drops 90% within 24 hours of entering the water, and furthermore that this loss in culturability is associated with a loss in virulence. Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a temperate bacteriophage . About 100 million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose, however, is less in those with lowered gastric acidity (for instance those using proton pump inhibitors ). Children are also more susceptible, with two- to four-year-olds having the highest rates of infection. Individuals' susceptibility to cholera is also affected by their blood type , with those with type O blood being the most susceptible. Persons with lowered immunity , such as persons with AIDS or malnourished children, are more likely to develop a severe case if they become infected. Any individual, even a healthy adult in middle age, can undergo a severe case, and each person's case should be measured by the loss of fluids, preferably in consultation with a professional health care provider . [ medical citation needed ] The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage : heterozygous carriers of the mutation (who are not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium , thus reducing the effects of an infection.Cholera bacteria have been found in shellfish and plankton . Transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation . Most cholera cases in developed countries are a result of transmission by food, while in developing countries it is more often water. Food transmission can occur when people harvest seafood such as oysters in waters infected with sewage , as Vibrio cholerae accumulates in planktonic crustaceans and the oysters eat the zooplankton . People infected with cholera often have diarrhea, and disease transmission may occur if this highly liquid stool, colloquially referred to as "rice-water", contaminates water used by others. A single diarrheal event can cause a one-million fold increase in numbers of V. cholerae in the environment. The source of the contamination is typically other people with cholera when their untreated diarrheal discharge is allowed to get into waterways, groundwater or drinking water supplies. Drinking any contaminated water and eating any foods washed in the water, as well as shellfish living in the affected waterway , can cause a person to contract an infection. Cholera is rarely spread directly from person to person . [note 1] V. cholerae also exists outside the human body in natural water sources, either by itself or through interacting with phytoplankton , zooplankton , or biotic and abiotic detritus. Drinking such water can also result in the disease, even without prior contamination through fecal matter. Selective pressures exist however in the aquatic environment that may reduce the virulence of V. cholerae . Specifically, animal models indicate that the transcriptional profile of the pathogen changes as it prepares to enter an aquatic environment. This transcriptional change results in a loss of ability of V. cholerae to be cultured on standard media, a phenotype referred to as ' viable but non-culturable ' (VBNC) or more conservatively ' active but non-culturable ' (ABNC). One study indicates that the culturability of V. cholerae drops 90% within 24 hours of entering the water, and furthermore that this loss in culturability is associated with a loss in virulence. Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a temperate bacteriophage . About 100 million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose, however, is less in those with lowered gastric acidity (for instance those using proton pump inhibitors ). Children are also more susceptible, with two- to four-year-olds having the highest rates of infection. Individuals' susceptibility to cholera is also affected by their blood type , with those with type O blood being the most susceptible. Persons with lowered immunity , such as persons with AIDS or malnourished children, are more likely to develop a severe case if they become infected. Any individual, even a healthy adult in middle age, can undergo a severe case, and each person's case should be measured by the loss of fluids, preferably in consultation with a professional health care provider . [ medical citation needed ] The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage : heterozygous carriers of the mutation (who are not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium , thus reducing the effects of an infection.When consumed, most bacteria do not survive the acidic conditions of the human stomach . The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down protein production. When the surviving bacteria exit the stomach and reach the small intestine , they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive. Once the cholera bacteria reach the intestinal wall, they no longer need the flagella to move. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea. This carries the multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place. The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits : a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond . The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins , while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis . Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein . This results in constitutive cAMP production, which in turn leads to the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer . Virulent strains of V. cholerae carry a variant of a temperate bacteriophage called CTXφ . Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria turn off the production of some proteins and turn on the production of other proteins as they respond to the series of chemical environments they encounter, passing through the stomach, through the mucous layer of the small intestine, and on to the intestinal wall. Of particular interest have been the genetic mechanisms by which cholera bacteria turn on the protein production of the toxins that interact with host cell mechanisms to pump chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The chloride and sodium ions create a salt-water environment in the small intestines, which through osmosis can pull up to six liters of water per day through the intestinal cells, creating the massive amounts of diarrhea. The host can become rapidly dehydrated unless treated properly. By inserting separate, successive sections of V. cholerae DNA into the DNA of other bacteria, such as E. coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of the stomach, mucous layers, and intestinal wall. Researchers have discovered a complex cascade of regulatory proteins controls expression of V. cholerae virulence determinants. In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce the toxins, causing diarrhea in the infected person and allowing the bacteria to colonize the intestine. Current [ when? ] research aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize (that is, adhere to the cells of) the small intestine." Amplified fragment length polymorphism fingerprinting of the pandemic isolates of V. cholerae has revealed variation in the genetic structure. Two clusters have been identified: Cluster I and Cluster II. For the most part, Cluster I consists of strains from the 1960s and 1970s, while Cluster II largely contains strains from the 1980s and 1990s, based on the change in the clone structure. This grouping of strains is best seen in the strains from the African continent. In many areas of the world, antibiotic resistance is increasing within cholera bacteria. In Bangladesh , for example, most cases are resistant to tetracycline , trimethoprim-sulfamethoxazole , and erythromycin . Rapid diagnostic assay methods are available for the identification of multi-drug resistant cases. New generation antimicrobials have been discovered which are effective against cholera bacteria in in vitro studies. Amplified fragment length polymorphism fingerprinting of the pandemic isolates of V. cholerae has revealed variation in the genetic structure. Two clusters have been identified: Cluster I and Cluster II. For the most part, Cluster I consists of strains from the 1960s and 1970s, while Cluster II largely contains strains from the 1980s and 1990s, based on the change in the clone structure. This grouping of strains is best seen in the strains from the African continent. In many areas of the world, antibiotic resistance is increasing within cholera bacteria. In Bangladesh , for example, most cases are resistant to tetracycline , trimethoprim-sulfamethoxazole , and erythromycin . Rapid diagnostic assay methods are available for the identification of multi-drug resistant cases. New generation antimicrobials have been discovered which are effective against cholera bacteria in in vitro studies. A rapid dipstick test is available to determine the presence of V. cholerae . In those samples that test positive, further testing should be done to determine antibiotic resistance. In epidemic situations, a clinical diagnosis may be made by taking a patient history and doing a brief examination. Treatment via hydration and over-the-counter hydration solutions can be started without or before confirmation by laboratory analysis, especially where cholera is a common problem. Stool and swab samples collected in the acute stage of the disease, before antibiotics have been administered, are the most useful specimens for laboratory diagnosis. If an epidemic of cholera is suspected, the most common causative agent is V. cholerae O1. If V. cholerae serogroup O1 is not isolated, the laboratory should test for V. cholerae O139. However, if neither of these organisms is isolated, it is necessary to send stool specimens to a reference laboratory. [ citation needed ] Infection with V. cholerae O139 should be reported and handled in the same manner as that caused by V. cholerae O1. The associated diarrheal illness should be referred to as cholera and must be reported in the United States. The World Health Organization (WHO) recommends focusing on prevention, preparedness, and response to combat the spread of cholera. They also stress the importance of an effective surveillance system. Governments can play a role in all of these areas. Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper sanitation practices are followed. In developed countries , due to their nearly universal advanced water treatment and sanitation practices, cholera is rare. For example, the last major outbreak of cholera in the United States occurred in 1910–1911. Cholera is mainly a risk in developing countries in those areas where access to WASH (water, sanitation and hygiene) infrastructure is still inadequate. Effective sanitation practices, if instituted and adhered to in time, are usually sufficient to stop an epidemic. There are several points along the cholera transmission path at which its spread may be halted: Handwashing with soap or ash after using a toilet and before handling food or eating is also recommended for cholera prevention by WHO Africa. Surveillance and prompt reporting allow for containing cholera epidemics rapidly. Cholera exists as a seasonal disease in many endemic countries, occurring annually mostly during rainy seasons . Surveillance systems can provide early alerts to outbreaks, therefore leading to coordinated response and assist in preparation of preparedness plans. Efficient surveillance systems can also improve the risk assessment for potential cholera outbreaks. Understanding the seasonality and location of outbreaks provides guidance for improving cholera control activities for the most vulnerable. For prevention to be effective, it is important that cases be reported to national health authorities. Spanish physician Jaume Ferran i Clua developed the first successful cholera inoculation in 1885, the first to immunize humans against a bacterial disease. His vaccine and inoculation was rather controversial and was rejected by his peers and several investigation commissions but it ended up demonstrating its effectiveness and being recognized for it: out of the 30 thousand people he vaccinated only 54 died. Russian-Jewish bacteriologist Waldemar Haffkine also developed a human cholera vaccine in July 1892. He conducted a massive inoculation program in British India . Persons who survive an episode of cholera have long-lasting immunity for at least 3 years (the period tested.) A number of safe and effective oral vaccines for cholera are available. The World Health Organization (WHO) has three prequalified oral cholera vaccines (OCVs): Dukoral, Sanchol, and Euvichol. Dukoral , an orally administered, inactivated whole-cell vaccine , has an overall efficacy of about 52% during the first year after being given and 62% in the second year, with minimal side effects. It is available in over 60 countries. However, it is not currently [ when? ] recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to endemic countries. The vaccine that the US Food and Drug Administration (FDA) recommends, Vaxchora , is an oral attenuated live vaccine , that is effective for adults aged 18–64 as a single dose. One injectable vaccine was found to be effective for two to three years. The protective efficacy was 28% lower in children less than five years old. However, as of 2010 [ update ] , it has limited availability. Work is under way to investigate the role of mass vaccination. The WHO recommends immunization of high-risk groups, such as children and people with HIV , in countries where this disease is endemic . If people are immunized broadly, herd immunity results, with a decrease in the amount of contamination in the environment. WHO recommends that oral cholera vaccination be considered in areas where the disease is endemic (with seasonal peaks), as part of the response to outbreaks, or in a humanitarian crisis during which the risk of cholera is high. Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. The World Health Organization (WHO) has prequalified three bivalent cholera vaccines—Dukoral (SBL Vaccines), containing a non-toxic B-subunit of cholera toxin and providing protection against V. cholerae O1; and two vaccines developed using the same transfer of technology—ShanChol (Shantha Biotec) and Euvichol (EuBiologics Co.), which have bivalent O1 and O139 oral killed cholera vaccines. Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. Developed for use in Bangladesh , the "sari filter" is a simple and cost-effective appropriate technology method for reducing the contamination of drinking water. Used sari cloth is preferable but other types of used cloth can be used with some effect, though the effectiveness will vary significantly. Used cloth is more effective than new cloth, as the repeated washing reduces the space between the fibers. Water collected in this way has a greatly reduced pathogen count—though it will not necessarily be perfectly safe, it is an improvement for poor people with limited options. In Bangladesh this practice was found to decrease rates of cholera by nearly half. It involves folding a sari four to eight times. Between uses the cloth should be rinsed in clean water and dried in the sun to kill any bacteria on it. A nylon cloth appears to work as well but is not as affordable. Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper sanitation practices are followed. In developed countries , due to their nearly universal advanced water treatment and sanitation practices, cholera is rare. For example, the last major outbreak of cholera in the United States occurred in 1910–1911. Cholera is mainly a risk in developing countries in those areas where access to WASH (water, sanitation and hygiene) infrastructure is still inadequate. Effective sanitation practices, if instituted and adhered to in time, are usually sufficient to stop an epidemic. There are several points along the cholera transmission path at which its spread may be halted: Handwashing with soap or ash after using a toilet and before handling food or eating is also recommended for cholera prevention by WHO Africa. Surveillance and prompt reporting allow for containing cholera epidemics rapidly. Cholera exists as a seasonal disease in many endemic countries, occurring annually mostly during rainy seasons . Surveillance systems can provide early alerts to outbreaks, therefore leading to coordinated response and assist in preparation of preparedness plans. Efficient surveillance systems can also improve the risk assessment for potential cholera outbreaks. Understanding the seasonality and location of outbreaks provides guidance for improving cholera control activities for the most vulnerable. For prevention to be effective, it is important that cases be reported to national health authorities. Spanish physician Jaume Ferran i Clua developed the first successful cholera inoculation in 1885, the first to immunize humans against a bacterial disease. His vaccine and inoculation was rather controversial and was rejected by his peers and several investigation commissions but it ended up demonstrating its effectiveness and being recognized for it: out of the 30 thousand people he vaccinated only 54 died. Russian-Jewish bacteriologist Waldemar Haffkine also developed a human cholera vaccine in July 1892. He conducted a massive inoculation program in British India . Persons who survive an episode of cholera have long-lasting immunity for at least 3 years (the period tested.) A number of safe and effective oral vaccines for cholera are available. The World Health Organization (WHO) has three prequalified oral cholera vaccines (OCVs): Dukoral, Sanchol, and Euvichol. Dukoral , an orally administered, inactivated whole-cell vaccine , has an overall efficacy of about 52% during the first year after being given and 62% in the second year, with minimal side effects. It is available in over 60 countries. However, it is not currently [ when? ] recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to endemic countries. The vaccine that the US Food and Drug Administration (FDA) recommends, Vaxchora , is an oral attenuated live vaccine , that is effective for adults aged 18–64 as a single dose. One injectable vaccine was found to be effective for two to three years. The protective efficacy was 28% lower in children less than five years old. However, as of 2010 [ update ] , it has limited availability. Work is under way to investigate the role of mass vaccination. The WHO recommends immunization of high-risk groups, such as children and people with HIV , in countries where this disease is endemic . If people are immunized broadly, herd immunity results, with a decrease in the amount of contamination in the environment. WHO recommends that oral cholera vaccination be considered in areas where the disease is endemic (with seasonal peaks), as part of the response to outbreaks, or in a humanitarian crisis during which the risk of cholera is high. Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. The World Health Organization (WHO) has prequalified three bivalent cholera vaccines—Dukoral (SBL Vaccines), containing a non-toxic B-subunit of cholera toxin and providing protection against V. cholerae O1; and two vaccines developed using the same transfer of technology—ShanChol (Shantha Biotec) and Euvichol (EuBiologics Co.), which have bivalent O1 and O139 oral killed cholera vaccines. Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. Developed for use in Bangladesh , the "sari filter" is a simple and cost-effective appropriate technology method for reducing the contamination of drinking water. Used sari cloth is preferable but other types of used cloth can be used with some effect, though the effectiveness will vary significantly. Used cloth is more effective than new cloth, as the repeated washing reduces the space between the fibers. Water collected in this way has a greatly reduced pathogen count—though it will not necessarily be perfectly safe, it is an improvement for poor people with limited options. In Bangladesh this practice was found to decrease rates of cholera by nearly half. It involves folding a sari four to eight times. Between uses the cloth should be rinsed in clean water and dried in the sun to kill any bacteria on it. A nylon cloth appears to work as well but is not as affordable. Continued eating speeds the recovery of normal intestinal function. The WHO recommends this generally for cases of diarrhea no matter what the underlying cause. A CDC training manual specifically for cholera states: "Continue to breastfeed your baby if the baby has watery diarrhea, even when traveling to get treatment. Adults and older children should continue to eat frequently." The most common error in caring for patients with cholera is to underestimate the speed and volume of fluids required. In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer. Rice-based solutions are preferred to glucose-based ones due to greater efficiency. In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate is the preferred solution, often with added potassium. Large volumes and continued replacement until diarrhea has subsided may be needed. Ten percent of a person's body weight in fluid may need to be given in the first two to four hours. This method was first tried on a mass scale during the Bangladesh Liberation War , and was found to have much success. Despite widespread beliefs, fruit juices and commercial fizzy drinks like cola are not ideal for rehydration of people with serious infections of the intestines, and their excessive sugar content may even harm water uptake. If commercially produced oral rehydration solutions are too expensive or difficult to obtain, solutions can be made. One such recipe calls for 1 liter of boiled water, 1/2 teaspoon of salt, 6 teaspoons of sugar, and added mashed banana for potassium and to improve taste. As there frequently is initially acidosis , the potassium level may be normal, even though large losses have occurred. As the dehydration is corrected, potassium levels may decrease rapidly, and thus need to be replaced. This may be done by consuming foods high in potassium, like bananas or coconut water. Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. Use of antibiotics also reduces fluid requirements. People will recover without them, however, if sufficient hydration is maintained. The WHO only recommends antibiotics in those with severe dehydration. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance . Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics proven to be effective include cotrimoxazole , erythromycin , tetracycline , chloramphenicol , and furazolidone . Fluoroquinolones , such as ciprofloxacin , also may be used, but resistance has been reported. Antibiotics improve outcomes in those who are both severely and not severely dehydrated. Azithromycin and tetracycline may work better than doxycycline or ciprofloxacin . In Bangladesh zinc supplementation reduced the duration and severity of diarrhea in children with cholera when given with antibiotics and rehydration therapy as needed. It reduced the length of disease by eight hours and the amount of diarrhea stool by 10%. Supplementation appears to be also effective in both treating and preventing infectious diarrhea due to other causes among children in the developing world. The most common error in caring for patients with cholera is to underestimate the speed and volume of fluids required. In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer. Rice-based solutions are preferred to glucose-based ones due to greater efficiency. In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate is the preferred solution, often with added potassium. Large volumes and continued replacement until diarrhea has subsided may be needed. Ten percent of a person's body weight in fluid may need to be given in the first two to four hours. This method was first tried on a mass scale during the Bangladesh Liberation War , and was found to have much success. Despite widespread beliefs, fruit juices and commercial fizzy drinks like cola are not ideal for rehydration of people with serious infections of the intestines, and their excessive sugar content may even harm water uptake. If commercially produced oral rehydration solutions are too expensive or difficult to obtain, solutions can be made. One such recipe calls for 1 liter of boiled water, 1/2 teaspoon of salt, 6 teaspoons of sugar, and added mashed banana for potassium and to improve taste. As there frequently is initially acidosis , the potassium level may be normal, even though large losses have occurred. As the dehydration is corrected, potassium levels may decrease rapidly, and thus need to be replaced. This may be done by consuming foods high in potassium, like bananas or coconut water. Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. Use of antibiotics also reduces fluid requirements. People will recover without them, however, if sufficient hydration is maintained. The WHO only recommends antibiotics in those with severe dehydration. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance . Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics proven to be effective include cotrimoxazole , erythromycin , tetracycline , chloramphenicol , and furazolidone . Fluoroquinolones , such as ciprofloxacin , also may be used, but resistance has been reported. Antibiotics improve outcomes in those who are both severely and not severely dehydrated. Azithromycin and tetracycline may work better than doxycycline or ciprofloxacin . In Bangladesh zinc supplementation reduced the duration and severity of diarrhea in children with cholera when given with antibiotics and rehydration therapy as needed. It reduced the length of disease by eight hours and the amount of diarrhea stool by 10%. Supplementation appears to be also effective in both treating and preventing infectious diarrhea due to other causes among children in the developing world. If people with cholera are treated quickly and properly, the mortality rate is less than 1%; however, with untreated cholera, the mortality rate rises to 50–60%. For certain genetic strains of cholera, such as the one present during the 2010 epidemic in Haiti and the 2004 outbreak in India, death can occur within two hours of becoming ill. Cholera affects an estimated 2.8 million people worldwide, and causes approximately 95,000 deaths a year (uncertainty range: 21,000–143,000) as of 2015 [ update ] . This occurs mainly in the developing world. In the early 1980s, death rates are believed to have still been higher than three million a year. It is difficult to calculate exact numbers of cases, as many go unreported due to concerns that an outbreak may have a negative impact on the tourism of a country. As of 2004, cholera remained both epidemic and endemic in many areas of the world. Recent major outbreaks are the 2010s Haiti cholera outbreak and the 2016–2022 Yemen cholera outbreak . In October 2016, an outbreak of cholera began in war-ravaged Yemen . WHO called it "the worst cholera outbreak in the world". In 2019, 93% of the reported 923,037 cholera cases were from Yemen (with 1911 deaths reported). Between September 2019 and September 2020, a global total of over 450,000 cases and over 900 deaths was reported; however, the accuracy of these numbers suffer from over-reporting from countries that report suspected cases (and not laboratory confirmed cases), as well as under-reporting from countries that do not report official cases (such as Bangladesh, India and Philippines). Although much is known about the mechanisms behind the spread of cholera, researchers still do not have a full understanding of what makes cholera outbreaks happen in some places and not others. Lack of treatment of human feces and lack of treatment of drinking water greatly facilitate its spread. Bodies of water have been found to serve as a reservoir of infection, and seafood shipped long distances can spread the disease. Cholera had disappeared from the Americas for most of the 20th century, but it reappeared toward the end of that century, beginning with a severe outbreak in Peru. This was followed by the 2010s Haiti cholera outbreak and another outbreak of cholera in Haiti amid the 2018–2023 Haitian crisis . As of August 2021 [ update ] the disease is endemic in Africa and some areas of eastern and western Asia (Bangladesh, India and Yemen). Cholera is not endemic in Europe; all reported cases had a travel history to endemic areas. The word cholera is from Greek : χολέρα kholera from χολή kholē "bile". Cholera likely has its origins in the Indian subcontinent as evidenced by its prevalence in the region for centuries. References to cholera appear in the European literature as early as 1642, from the Dutch physician Jakob de Bondt's description in his De Medicina Indorum. (The "Indorum" of the title refers to the East Indies. He also gave first European descriptions of other diseases.) But at the time, the word "cholera" was historically used by European physicians to refer to any gastrointestinal upset resulting in yellow diarrhea. De Bondt thus used a common word already in regular use to describe the new disease. This was a frequent practice of the time. It was not until the 1830s that the name for severe yellow diarrhea changed in English from "cholera" to "cholera morbus" to differentiate it from what was then known as "Asiatic cholera", or that associated with origins in India and the East. Early outbreaks in the Indian subcontinent are believed to have been the result of crowded, poor living conditions, as well as the presence of pools of still water , both of which provide ideal conditions for cholera to thrive. The disease first spread by travelers along trade routes (land and sea) to Russia in 1817, later to the rest of Europe , and from Europe to North America and the rest of the world, (hence the name "Asiatic cholera" ). Seven cholera pandemics have occurred since the early 19th century; the first one did not reach the Americas. The seventh pandemic originated in Indonesia in 1961. The first cholera pandemic occurred in the Bengal region of India, near Calcutta starting in 1817 through 1824. The disease dispersed from India to Southeast Asia, the Middle East, Europe, and Eastern Africa. The movement of British Army and Navy ships and personnel is believed to have contributed to the range of the pandemic, since the ships carried people with the disease to the shores of the Indian Ocean, from Africa to Indonesia, and north to China and Japan. The second pandemic lasted from 1826 to 1837 and particularly affected North America and Europe. Advancements in transportation and global trade, and increased human migration, including soldiers, meant that more people were carrying the disease more widely. The third pandemic erupted in 1846, persisted until 1860, extended to North Africa, and reached North and South America. It was introduced to North America at Quebec, Canada , via Irish immigrants from the Great Famine. In this pandemic, Brazil was affected for the first time. The fourth pandemic lasted from 1863 to 1875, spreading from India to Naples and Spain, and reaching the United States at New Orleans, Louisiana in 1873. It spread throughout the Mississippi River system on the continent. The fifth pandemic was from 1881 to 1896. It started in India and spread to Europe, Asia, and South America. The sixth pandemic ran from 1899 to 1923. These epidemics had a lower number of fatalities because physicians and researchers had a greater understanding of the cholera bacteria. Egypt, the Arabian peninsula, Persia, India, and the Philippines were hit hardest during these epidemics. Other areas, such as Germany in 1892 (primarily the city of Hamburg, where more than 8.600 people died) and Naples from 1910 to 1911, also had severe outbreaks. The seventh pandemic originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed El Tor , which still persists ( as of 2018 [ update ] ) in developing countries. This pandemic had initially subsided about 1975 and was thought to have ended, but, as noted, it has persisted. There were a rise in cases in the 1990s and since. Cholera became widespread in the 19th century. Since then it has killed tens of millions of people. In Russia alone, between 1847 and 1851, more than one million people died from the disease. It killed 150,000 Americans during the second pandemic. Between 1900 and 1920, perhaps eight million people died of cholera in India. Cholera officially became the first reportable disease in the United States due to the significant effects it had on health. John Snow , in England , in 1854 was the first to identify the importance of contaminated water as its source of transmission. Cholera is now no longer considered a pressing health threat in Europe and North America due to filtering and chlorination of water supplies, but it still strongly affects populations in developing countries . In the past, vessels flew a yellow quarantine flag if any crew members or passengers had cholera. No one aboard a vessel flying a yellow flag would be allowed ashore for an extended period, typically 30 to 40 days. Historically many different claimed remedies have existed in folklore. Many of the older remedies were based on the miasma theory , that the disease was transmitted by bad air. Some believed that abdominal chilling made one more susceptible, and flannel and cholera belts were included in army kits. In the 1854–1855 outbreak in Naples, homeopathic camphor was used according to Hahnemann . .Dr Hahnemann laid down three main remedies that would be curative in that disease; in early and simple cases camphor ; in later stages with excessive cramping, cuprum or with excessive evacuations and profuse cold sweat, veratrum album . These are the Trio Cholera remedies used by homoeopaths around the world. T. J. Ritter's Mother's Remedies book lists tomato syrup as a home remedy from northern America. Elecampane was recommended in the United Kingdom, according to William Thomas Fernie. The first effective human vaccine was developed in 1885, and the first effective antibiotic was developed in 1948. Cholera cases are much less frequent in developed countries where governments have helped to establish water sanitation practices and effective medical treatments. In the 19th century the United States, for example, had a severe cholera problem similar to those in some developing countries. It had three large cholera outbreaks in the 1800s, which can be attributed to Vibrio cholerae ' s spread through interior waterways such as the Erie Canal and the extensive Mississippi River valley system, as well as the major ports along the Eastern Seaboard and their cities upriver. The island of Manhattan in New York City touches the Atlantic Ocean, where cholera collected from river waters and ship discharges just off the coast. At this time, New York City did not have as effective a sanitation system as it developed in the later 20th century, so cholera spread through the city's water supply. Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically to what is now defined as the disease of cholera. One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist John Snow (1813–1858), who in 1854 found a link between cholera and contaminated drinking water. Dr. Snow proposed a microbial origin for epidemic cholera in 1849. In his major "state of the art" review of 1855, he proposed a substantially complete and correct model for the cause of the disease. In two pioneering epidemiological field studies, he was able to demonstrate human sewage contamination was the most probable disease vector in two major epidemics in London in 1854 . His model was not immediately accepted, but it was increasingly seen as plausible as medical microbiology developed over the next 30 years or so. For his work on cholera, John Snow is often regarded as the "Father of Epidemiology". The bacterium was isolated in 1854 by Italian anatomist Filippo Pacini , but its exact nature and his results were not widely known. In the same year, the Catalan Joaquim Balcells i Pascual discovered the bacterium. In 1856 António Augusto da Costa Simões and José Ferreira de Macedo Pinto , two Portuguese researchers, are believed to have done the same. Between the mid-1850s and the 1900s, cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1883, Robert Koch identified V. cholerae with a microscope as the bacillus causing the disease. Hemendra Nath Chatterjee , a Bengali scientist, was the first to formulate and demonstrate the effectiveness of oral rehydration salt (ORS) to treat diarrhea . In his 1953 paper, published in The Lancet , he states that promethazine can stop vomiting during cholera and then oral rehydration is possible. The formulation of the fluid replacement solution was 4 g of sodium chloride , 25 g of glucose and 1000 ml of water . Indian medical scientist Sambhu Nath De discovered the cholera toxin , the animal model of cholera , and successfully demonstrated the method of transmission of cholera pathogen Vibrio cholerae . Robert Allan Phillips , working at US Naval Medical Research Unit Two in Southeast Asia, evaluated the pathophysiology of the disease using modern laboratory chemistry techniques. He developed a protocol for rehydration. His research led the Lasker Foundation to award him its prize in 1967. More recently, in 2002, Alam, et al. , studied stool samples from patients at the International Centre for Diarrhoeal Disease in Dhaka, Bangladesh . From the various experiments they conducted, the researchers found a correlation between the passage of V. cholerae through the human digestive system and an increased infectivity state. Furthermore, the researchers found the bacterium creates a hyperinfected state where genes that control biosynthesis of amino acids , iron uptake systems, and formation of periplasmic nitrate reductase complexes were induced just before defecation. These induced characteristics allow the cholera vibrios to survive in the "rice water" stools, an environment of limited oxygen and iron, of patients with a cholera infection. In 2017, the WHO launched the "Ending Cholera: a global roadmap to 2030" strategy which aims to reduce cholera deaths by 90% by 2030. The strategy was developed by the Global Task Force on Cholera Control (GTFCC) which develops country-specific plans and monitors progress. The approach to achieve this goal combines surveillance, water sanitation, rehydration treatment and oral vaccines. Specifically, the control strategy focuses on three approaches: i) early detection and response to outbreaks to contain outbreaks, ii) stopping cholera transmission through improved sanitation and vaccines in hotspots, and iii) a global framework for cholera control through the GTFCC. The WHO and the GTFCC do not consider global cholera eradication a viable goal. Even though humans are the only host of cholera, the bacterium can persist in the environment without a human host. While global eradication is not possible, elimination of human to human transmission may be possible. Local elimination is possible, which has been underway most recently during the 2010s Haiti cholera outbreak . Haiti aims to achieve certification of elimination by 2022. The GTFCC targets 47 countries, 13 of which have established vaccination campaigns. The word cholera is from Greek : χολέρα kholera from χολή kholē "bile". Cholera likely has its origins in the Indian subcontinent as evidenced by its prevalence in the region for centuries. References to cholera appear in the European literature as early as 1642, from the Dutch physician Jakob de Bondt's description in his De Medicina Indorum. (The "Indorum" of the title refers to the East Indies. He also gave first European descriptions of other diseases.) But at the time, the word "cholera" was historically used by European physicians to refer to any gastrointestinal upset resulting in yellow diarrhea. De Bondt thus used a common word already in regular use to describe the new disease. This was a frequent practice of the time. It was not until the 1830s that the name for severe yellow diarrhea changed in English from "cholera" to "cholera morbus" to differentiate it from what was then known as "Asiatic cholera", or that associated with origins in India and the East. Early outbreaks in the Indian subcontinent are believed to have been the result of crowded, poor living conditions, as well as the presence of pools of still water , both of which provide ideal conditions for cholera to thrive. The disease first spread by travelers along trade routes (land and sea) to Russia in 1817, later to the rest of Europe , and from Europe to North America and the rest of the world, (hence the name "Asiatic cholera" ). Seven cholera pandemics have occurred since the early 19th century; the first one did not reach the Americas. The seventh pandemic originated in Indonesia in 1961. The first cholera pandemic occurred in the Bengal region of India, near Calcutta starting in 1817 through 1824. The disease dispersed from India to Southeast Asia, the Middle East, Europe, and Eastern Africa. The movement of British Army and Navy ships and personnel is believed to have contributed to the range of the pandemic, since the ships carried people with the disease to the shores of the Indian Ocean, from Africa to Indonesia, and north to China and Japan. The second pandemic lasted from 1826 to 1837 and particularly affected North America and Europe. Advancements in transportation and global trade, and increased human migration, including soldiers, meant that more people were carrying the disease more widely. The third pandemic erupted in 1846, persisted until 1860, extended to North Africa, and reached North and South America. It was introduced to North America at Quebec, Canada , via Irish immigrants from the Great Famine. In this pandemic, Brazil was affected for the first time. The fourth pandemic lasted from 1863 to 1875, spreading from India to Naples and Spain, and reaching the United States at New Orleans, Louisiana in 1873. It spread throughout the Mississippi River system on the continent. The fifth pandemic was from 1881 to 1896. It started in India and spread to Europe, Asia, and South America. The sixth pandemic ran from 1899 to 1923. These epidemics had a lower number of fatalities because physicians and researchers had a greater understanding of the cholera bacteria. Egypt, the Arabian peninsula, Persia, India, and the Philippines were hit hardest during these epidemics. Other areas, such as Germany in 1892 (primarily the city of Hamburg, where more than 8.600 people died) and Naples from 1910 to 1911, also had severe outbreaks. The seventh pandemic originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed El Tor , which still persists ( as of 2018 [ update ] ) in developing countries. This pandemic had initially subsided about 1975 and was thought to have ended, but, as noted, it has persisted. There were a rise in cases in the 1990s and since. Cholera became widespread in the 19th century. Since then it has killed tens of millions of people. In Russia alone, between 1847 and 1851, more than one million people died from the disease. It killed 150,000 Americans during the second pandemic. Between 1900 and 1920, perhaps eight million people died of cholera in India. Cholera officially became the first reportable disease in the United States due to the significant effects it had on health. John Snow , in England , in 1854 was the first to identify the importance of contaminated water as its source of transmission. Cholera is now no longer considered a pressing health threat in Europe and North America due to filtering and chlorination of water supplies, but it still strongly affects populations in developing countries . In the past, vessels flew a yellow quarantine flag if any crew members or passengers had cholera. No one aboard a vessel flying a yellow flag would be allowed ashore for an extended period, typically 30 to 40 days. Historically many different claimed remedies have existed in folklore. Many of the older remedies were based on the miasma theory , that the disease was transmitted by bad air. Some believed that abdominal chilling made one more susceptible, and flannel and cholera belts were included in army kits. In the 1854–1855 outbreak in Naples, homeopathic camphor was used according to Hahnemann . .Dr Hahnemann laid down three main remedies that would be curative in that disease; in early and simple cases camphor ; in later stages with excessive cramping, cuprum or with excessive evacuations and profuse cold sweat, veratrum album . These are the Trio Cholera remedies used by homoeopaths around the world. T. J. Ritter's Mother's Remedies book lists tomato syrup as a home remedy from northern America. Elecampane was recommended in the United Kingdom, according to William Thomas Fernie. The first effective human vaccine was developed in 1885, and the first effective antibiotic was developed in 1948. Cholera cases are much less frequent in developed countries where governments have helped to establish water sanitation practices and effective medical treatments. In the 19th century the United States, for example, had a severe cholera problem similar to those in some developing countries. It had three large cholera outbreaks in the 1800s, which can be attributed to Vibrio cholerae ' s spread through interior waterways such as the Erie Canal and the extensive Mississippi River valley system, as well as the major ports along the Eastern Seaboard and their cities upriver. The island of Manhattan in New York City touches the Atlantic Ocean, where cholera collected from river waters and ship discharges just off the coast. At this time, New York City did not have as effective a sanitation system as it developed in the later 20th century, so cholera spread through the city's water supply. Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically to what is now defined as the disease of cholera. One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist John Snow (1813–1858), who in 1854 found a link between cholera and contaminated drinking water. Dr. Snow proposed a microbial origin for epidemic cholera in 1849. In his major "state of the art" review of 1855, he proposed a substantially complete and correct model for the cause of the disease. In two pioneering epidemiological field studies, he was able to demonstrate human sewage contamination was the most probable disease vector in two major epidemics in London in 1854 . His model was not immediately accepted, but it was increasingly seen as plausible as medical microbiology developed over the next 30 years or so. For his work on cholera, John Snow is often regarded as the "Father of Epidemiology". The bacterium was isolated in 1854 by Italian anatomist Filippo Pacini , but its exact nature and his results were not widely known. In the same year, the Catalan Joaquim Balcells i Pascual discovered the bacterium. In 1856 António Augusto da Costa Simões and José Ferreira de Macedo Pinto , two Portuguese researchers, are believed to have done the same. Between the mid-1850s and the 1900s, cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1883, Robert Koch identified V. cholerae with a microscope as the bacillus causing the disease. Hemendra Nath Chatterjee , a Bengali scientist, was the first to formulate and demonstrate the effectiveness of oral rehydration salt (ORS) to treat diarrhea . In his 1953 paper, published in The Lancet , he states that promethazine can stop vomiting during cholera and then oral rehydration is possible. The formulation of the fluid replacement solution was 4 g of sodium chloride , 25 g of glucose and 1000 ml of water . Indian medical scientist Sambhu Nath De discovered the cholera toxin , the animal model of cholera , and successfully demonstrated the method of transmission of cholera pathogen Vibrio cholerae . Robert Allan Phillips , working at US Naval Medical Research Unit Two in Southeast Asia, evaluated the pathophysiology of the disease using modern laboratory chemistry techniques. He developed a protocol for rehydration. His research led the Lasker Foundation to award him its prize in 1967. More recently, in 2002, Alam, et al. , studied stool samples from patients at the International Centre for Diarrhoeal Disease in Dhaka, Bangladesh . From the various experiments they conducted, the researchers found a correlation between the passage of V. cholerae through the human digestive system and an increased infectivity state. Furthermore, the researchers found the bacterium creates a hyperinfected state where genes that control biosynthesis of amino acids , iron uptake systems, and formation of periplasmic nitrate reductase complexes were induced just before defecation. These induced characteristics allow the cholera vibrios to survive in the "rice water" stools, an environment of limited oxygen and iron, of patients with a cholera infection. In 2017, the WHO launched the "Ending Cholera: a global roadmap to 2030" strategy which aims to reduce cholera deaths by 90% by 2030. The strategy was developed by the Global Task Force on Cholera Control (GTFCC) which develops country-specific plans and monitors progress. The approach to achieve this goal combines surveillance, water sanitation, rehydration treatment and oral vaccines. Specifically, the control strategy focuses on three approaches: i) early detection and response to outbreaks to contain outbreaks, ii) stopping cholera transmission through improved sanitation and vaccines in hotspots, and iii) a global framework for cholera control through the GTFCC. The WHO and the GTFCC do not consider global cholera eradication a viable goal. Even though humans are the only host of cholera, the bacterium can persist in the environment without a human host. While global eradication is not possible, elimination of human to human transmission may be possible. Local elimination is possible, which has been underway most recently during the 2010s Haiti cholera outbreak . Haiti aims to achieve certification of elimination by 2022. The GTFCC targets 47 countries, 13 of which have established vaccination campaigns. In many developing countries, cholera still reaches its victims through contaminated water sources, and countries without proper sanitation techniques have greater incidence of the disease. Governments can play a role in this. In 2008, for example, the Zimbabwean cholera outbreak was due partly to the government's role, according to a report from the James Baker Institute . The Haitian government's inability to provide safe drinking water after the 2010 earthquake led to an increase in cholera cases as well. Similarly, South Africa's cholera outbreak was exacerbated by the government's policy of privatizing water programs. The wealthy elite of the country were able to afford safe water while others had to use water from cholera-infected rivers. According to Rita R. Colwell of the James Baker Institute , if cholera does begin to spread, government preparedness is crucial. A government's ability to contain the disease before it extends to other areas can prevent a high death toll and the development of an epidemic or even pandemic. Effective disease surveillance can ensure that cholera outbreaks are recognized as soon as possible and dealt with appropriately. Oftentimes, this will allow public health programs to determine and control the cause of the cases, whether it is unsanitary water or seafood that have accumulated a lot of Vibrio cholerae specimens. Having an effective surveillance program contributes to a government's ability to prevent cholera from spreading. In the year 2000 in the state of Kerala in India, the Kottayam district was determined to be "Cholera-affected"; this pronouncement led to task forces that concentrated on educating citizens with 13,670 information sessions about human health. These task forces promoted the boiling of water to obtain safe water, and provided chlorine and oral rehydration salts. Ultimately, this helped to control the spread of the disease to other areas and minimize deaths. On the other hand, researchers have shown that most of the citizens infected during the 1991 cholera outbreak in Bangladesh lived in rural areas, and were not recognized by the government's surveillance program. This inhibited physicians' abilities to detect cholera cases early. According to Colwell, the quality and inclusiveness of a country's health care system affects the control of cholera, as it did in the Zimbabwean cholera outbreak . While sanitation practices are important, when governments respond quickly and have readily available vaccines, the country will have a lower cholera death toll. Affordability of vaccines can be a problem; if the governments do not provide vaccinations, only the wealthy may be able to afford them and there will be a greater toll on the country's poor. The speed with which government leaders respond to cholera outbreaks is important. Besides contributing to an effective or declining public health care system and water sanitation treatments, government can have indirect effects on cholera control and the effectiveness of a response to cholera. A country's government can impact its ability to prevent disease and control its spread. A speedy government response backed by a fully functioning health care system and financial resources can prevent cholera's spread. This limits cholera's ability to cause death, or at the very least a decline in education, as children are kept out of school to minimize the risk of infection. Inversely, poor government response can lead to civil unrest and cholera riots . Unlike tuberculosis ("consumption") which in literature and the arts was often romanticized as a disease of denizens of the demimonde or those with an artistic temperament, cholera is a disease which almost entirely affects the poor living in unsanitary conditions. This, and the unpleasant course of the disease – which includes voluminous "rice-water" diarrhea, the hemorrhaging of liquids from the mouth, and violent muscle contractions which continue even after death – has discouraged the disease from being romanticized, or even being factually presented in popular culture. In many developing countries, cholera still reaches its victims through contaminated water sources, and countries without proper sanitation techniques have greater incidence of the disease. Governments can play a role in this. In 2008, for example, the Zimbabwean cholera outbreak was due partly to the government's role, according to a report from the James Baker Institute . The Haitian government's inability to provide safe drinking water after the 2010 earthquake led to an increase in cholera cases as well. Similarly, South Africa's cholera outbreak was exacerbated by the government's policy of privatizing water programs. The wealthy elite of the country were able to afford safe water while others had to use water from cholera-infected rivers. According to Rita R. Colwell of the James Baker Institute , if cholera does begin to spread, government preparedness is crucial. A government's ability to contain the disease before it extends to other areas can prevent a high death toll and the development of an epidemic or even pandemic. Effective disease surveillance can ensure that cholera outbreaks are recognized as soon as possible and dealt with appropriately. Oftentimes, this will allow public health programs to determine and control the cause of the cases, whether it is unsanitary water or seafood that have accumulated a lot of Vibrio cholerae specimens. Having an effective surveillance program contributes to a government's ability to prevent cholera from spreading. In the year 2000 in the state of Kerala in India, the Kottayam district was determined to be "Cholera-affected"; this pronouncement led to task forces that concentrated on educating citizens with 13,670 information sessions about human health. These task forces promoted the boiling of water to obtain safe water, and provided chlorine and oral rehydration salts. Ultimately, this helped to control the spread of the disease to other areas and minimize deaths. On the other hand, researchers have shown that most of the citizens infected during the 1991 cholera outbreak in Bangladesh lived in rural areas, and were not recognized by the government's surveillance program. This inhibited physicians' abilities to detect cholera cases early. According to Colwell, the quality and inclusiveness of a country's health care system affects the control of cholera, as it did in the Zimbabwean cholera outbreak . While sanitation practices are important, when governments respond quickly and have readily available vaccines, the country will have a lower cholera death toll. Affordability of vaccines can be a problem; if the governments do not provide vaccinations, only the wealthy may be able to afford them and there will be a greater toll on the country's poor. The speed with which government leaders respond to cholera outbreaks is important. Besides contributing to an effective or declining public health care system and water sanitation treatments, government can have indirect effects on cholera control and the effectiveness of a response to cholera. A country's government can impact its ability to prevent disease and control its spread. A speedy government response backed by a fully functioning health care system and financial resources can prevent cholera's spread. This limits cholera's ability to cause death, or at the very least a decline in education, as children are kept out of school to minimize the risk of infection. Inversely, poor government response can lead to civil unrest and cholera riots . Unlike tuberculosis ("consumption") which in literature and the arts was often romanticized as a disease of denizens of the demimonde or those with an artistic temperament, cholera is a disease which almost entirely affects the poor living in unsanitary conditions. This, and the unpleasant course of the disease – which includes voluminous "rice-water" diarrhea, the hemorrhaging of liquids from the mouth, and violent muscle contractions which continue even after death – has discouraged the disease from being romanticized, or even being factually presented in popular culture. In Zambia , widespread cholera outbreaks have occurred since 1977, most commonly in the capital city of Lusaka . In 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool samples from two patients with acute watery diarrhea. There was a rapid increase in the number of cases from several hundred cases in early December 2017 to approximately 2,000 by early January 2018. With intensification of the rains, new cases increased on a daily basis reaching a peak on the first week of January 2018 with over 700 cases reported. In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December. The city of Kolkata , India in the state of West Bengal in the Ganges delta has been described as the "homeland of cholera", with regular outbreaks and pronounced seasonality. In India, where the disease is endemic , cholera outbreaks occur every year between dry seasons and rainy seasons . India is also characterized by high population density, unsafe drinking water, open drains, and poor sanitation which provide an optimal niche for survival, sustenance and transmission of Vibrio cholerae . In Goma in the Democratic Republic of Congo , cholera has left an enduring mark on human and medical history. Cholera pandemics in the 19th and 20th centuries led to the growth of epidemiology as a science and in recent years it has continued to press advances in the concepts of disease ecology , basic membrane biology, and transmembrane signaling and in the use of scientific information and treatment design. In Zambia , widespread cholera outbreaks have occurred since 1977, most commonly in the capital city of Lusaka . In 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool samples from two patients with acute watery diarrhea. There was a rapid increase in the number of cases from several hundred cases in early December 2017 to approximately 2,000 by early January 2018. With intensification of the rains, new cases increased on a daily basis reaching a peak on the first week of January 2018 with over 700 cases reported. In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December. The city of Kolkata , India in the state of West Bengal in the Ganges delta has been described as the "homeland of cholera", with regular outbreaks and pronounced seasonality. In India, where the disease is endemic , cholera outbreaks occur every year between dry seasons and rainy seasons . India is also characterized by high population density, unsafe drinking water, open drains, and poor sanitation which provide an optimal niche for survival, sustenance and transmission of Vibrio cholerae . In Goma in the Democratic Republic of Congo , cholera has left an enduring mark on human and medical history. Cholera pandemics in the 19th and 20th centuries led to the growth of epidemiology as a science and in recent years it has continued to press advances in the concepts of disease ecology , basic membrane biology, and transmembrane signaling and in the use of scientific information and treatment design.

Wiki

Cholera

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

History of cholera

Seven cholera pandemics have occurred in the past 200 years, with the first pandemic originating in India in 1817. The seventh cholera pandemic is officially a current pandemic and has been ongoing since 1961, according to a World Health Organization factsheet in March 2022. Additionally, there have been many documented major local cholera outbreaks, such as a 1991–1994 outbreak in South America and, more recently, the 2016–2021 Yemen cholera outbreak . Although much is known about the mechanisms behind the spread of cholera , this has not led to a full understanding of what makes cholera outbreaks happen in some places and not others. Lack of treatment of human feces and lack of treatment of drinking water greatly facilitate its spread. Bodies of water have been found to serve as a reservoir , and seafood shipped long distances can spread the disease. Between 1816 and 1923, the first six cholera pandemics occurred consecutively and continuously over time. Increased commerce, migration, and pilgrimage are credited for its transmission. Late in this period (particularly 1879–1883), major scientific breakthroughs toward the treatment of cholera develop: the first immunization by Pasteur , the development of the first cholera vaccine, and identification of the bacterium Vibrio cholerae by Filippo Pacini and Robert Koch . After a long hiatus, a seventh cholera pandemic spread in 1961. The pandemic subsided in the 1970s, but continued on a smaller scale. Outbreaks occur across the developing world to the current day. Epidemics occurred after wars, civil unrest, or natural disasters, when water and food supplies had become contaminated with Vibrio cholerae , and also due to crowded living conditions and poor sanitation. Deaths in India between 1817 and 1860 in the first three pandemics of the nineteenth century, are estimated to have exceeded 15 million people. Another 23 million died between 1865 and 1917, during the next three pandemics. Cholera deaths in the Russian Empire during a similar time period exceeded 2 million. The first cholera pandemic occurred in the Bengal region of India, near Calcutta (now Kolkata), starting in 1817 through 1824. The disease dispersed from India to Southeast Asia, the Middle East, Europe, and Eastern Africa through trade routes. The second pandemic lasted from 1826 to 1837 and particularly affected North America and Europe, due to the result of advancements in transportation and global trade, and increased human migration, including soldiers. The third pandemic erupted in 1846, persisted until 1860, extended to North Africa, and reached South America, for the first time specifically affecting Brazil. The fourth pandemic lasted from 1863 to 1875, and spread from India to Naples and Spain , and to the United States in 1873. The fifth pandemic was from 1881 to 1896 and started in India and spread to Europe, Asia, and South America. The sixth pandemic started in India and lasted from 1899 to 1923. These epidemics were less fatal due to a greater understanding of the cholera bacteria. Egypt, the Arabian peninsula, Persia, India, and the Philippines were hit hardest during these epidemics, while other areas, such as Germany in 1892 and Naples from 1910 to 1911, also suffered severe outbreaks. The seventh pandemic originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed El Tor , which still persists (as of 2019 ) in developing countries. Cholera did not occur in the Americas for most of the 20th century after the early 1900s in New York City. It reappeared in the Caribbean toward the end of that century and seems likely to persist. The first cholera pandemic , though previously restricted, began in Bengal , and then spread across India by 1820. Hundreds of thousands of Indians and ten thousand British troops died during this pandemic. The cholera outbreak extended as far as China , Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea in Europe, before receding. In 1821, it is estimated that up to 100,000 deaths occurred in Korea . A second cholera pandemic reached Russia (see Cholera Riots ), Hungary (about 100,000 deaths) and Germany in 1831; it killed 130,000 people in Egypt that year. In 1832 it reached London and the United Kingdom (where more than 55,000 people died) and Paris . In London, the disease claimed 6,536 victims and came to be known as "King Cholera"; in Paris, 20,000 died (of a population of 650,000), and total deaths in France amounted to 100,000. In 1833, a cholera epidemic killed many Pomo , which are a Native American tribe. The epidemic reached Quebec , Ontario , Nova Scotia , and New York in the same year, and the Pacific coast of North America by 1834. In the center of the country [ clarification needed ] , it spread through the cities linked by the rivers and steamboat traffic. In Washington D.C. Michael Shiner , an enslaved laborer at the Washington Navy Yard recorded, "The time the colery [cholera] broke out in about June and July August and September 1832 it Raged in the City of Washington and every day they wher [were] twelve or 13 carried out to they [their] graves a day." By late July 1832, cholera had spread to Virginia and on 7 August 1832, Commodore Lewis Warrington confirmed to the Secretary of the Navy Levi Woodbury cholera was at the Gosport Navy Yard , "Between noon of that day, [1 August] and the morning of Friday [3 August], when all work on board her USS Fairchild stopped, several deaths by cholera occurred and fifteen or sixteen cases (of less violence) were reported." The epidemic of cholera, cause unknown and prognosis dire, had reached its peak. Cholera afflicted Mexico's populations in 1833 and 1850, prompting officials to quarantine some populations and fumigate buildings, particularly in major urban centers, but nonetheless the epidemics were disastrous. During this pandemic, the scientific community varied in its beliefs about the causes of cholera. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious, although doctors did not understand how it spread. The United States believed that cholera was brought by recent immigrants, specifically the Irish, and epidemiologists understand they were carrying disease from British ports. Lastly, some British thought the disease might rise from divine intervention. The social importance of the government having a direct role in the development and application of science was demonstrated through the U.S. government's support of efforts to control the epidemic. The third cholera pandemic deeply affected Russia, with over one million deaths. Over 15,000 people died of cholera in Mecca in 1846. A two-year outbreak began in England and Wales in 1848, and claimed 52,000 lives. In 1849, a second major outbreak occurred in France. In London, it was the worst outbreak in the city's history, claiming 14,137 lives, over twice as many as the 1832 outbreak. Cholera hit Ireland in 1849 and killed many of the Irish Famine survivors, already weakened by starvation and fever. In 1849, cholera claimed 5,308 lives in the major port city of Liverpool , England , an embarkation point for immigrants to North America, and 1,834 in Hull , England. In Vietnam and Cambodia, cholera hit in summer 1849, killing approximately 589,000 to 800,000 people within one year, along with its consequential famine. An outbreak in North America took the life of former U.S. President James K. Polk . Cholera, believed spread from Irish immigrant ships from England, spread throughout the Mississippi river system , killing over 4,500 in St. Louis and over 3,000 in New Orleans . Thousands died in New York , a major destination for Irish immigrants. Cholera claimed 200,000 victims in Mexico . That year, cholera was transmitted along the California , Mormon , and Oregon Trails as 6,000 to 12,000 are believed to have died on their way to the California Gold Rush , Utah and Oregon in the cholera years of 1849–1855. It is believed more than 150,000 Americans died during the two pandemics between 1832 and 1849. In 1851, a ship coming from Cuba carried the disease to Gran Canaria . It is considered that more than 6,000 people died in the island during summer, out of a population of 58,000. In 1852, cholera spread east to the Dutch East Indies and later was carried to Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal contributed to transmission of the disease by travelers and troops to Iran , Iraq , Arabia , and Russia. Japan suffered at least seven major outbreaks of cholera between 1858 and 1902. Between 100,000 and 200,000 people died of cholera in Tokyo in an outbreak in 1858–1860. In 1854, an outbreak of cholera in Chicago took the lives of 5.5 percent of the population (about 3,500 people). Providence, Rhode Island , suffered an outbreak so widespread that for the next thirty years, 1854 was known there as "The Year of Cholera." In 1853–1854, London's epidemic claimed 10,739 lives. The 1854 Broad Street Cholera outbreak in London ended after the physician John Snow identified a neighborhood Broad Street pump as contaminated and convinced officials to remove its handle to prevent people from drawing water there. His study proved contaminated water was the main agent spreading cholera, although he did not identify the contaminant. It would take many years for this message to be believed and fully acted upon. In Spain , over 236,000 died of cholera in the epidemic of 1854–1855. The disease reached South America in 1854 and 1855, with victims in Venezuela and Brazil. During the third pandemic, residents of Tunisia , which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. Some United States scientists began to believe that cholera was somehow associated with African Americans, as the disease was prevalent in the South in areas of black populations. Current researchers note their populations were underserved in terms of sanitation infrastructure and health care, and they lived near the waterways by which travelers and ships carried the disease. From November 10, 1855, to December 1856, the disease spread through Puerto Rico, claiming 25,820 victims. Cemeteries were expanded to allow for the burial of victims of cholera. In Arecibo , a large municipality of Puerto Rico, the number of people dying in the streets was so great that the city could not keep up. A man named Ulanga made it his responsibility to collect and carry the dead to the provisional Cementerio de los Coléricos . The fourth cholera pandemic of the century began in the Ganges Delta of the Bengal region and traveled with Muslim pilgrims to Mecca . In its first year, the epidemic claimed 30,000 of 90,000 Mecca pilgrims. Cholera spread throughout the Middle East and was carried to Russia, Europe, Africa and North America, in each case spreading from port cities and along inland waterways. [ citation needed ] The pandemic reached Northern Africa in 1865 and spread to sub-Saharan Africa, killing 70,000 in Zanzibar in 1869–1870. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have taken 165,000 lives in the Austrian Empire , including 30,000 each in Hungary and Belgium and 20,000 in the Netherlands. Other deaths from cholera at the time included 115,000 in Germany, 90,000 in Russia, and 30,000 in Belgium. In London in June 1866, a localized epidemic in the East End claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems (see London sewerage system ); the East End section was not quite complete. Epidemiologist William Farr identified the East London Water Company as the source of the contamination. Farr made use of prior work by John Snow and others pointing to contaminated drinking water as the likely cause of cholera in an 1854 outbreak . Quick action prevented further deaths. In the same year, the use of contaminated canal water in local water works caused a minor outbreak at Ystalyfera in South Wales. Workers associated with the company and their families were most affected, and 119 died. [ citation needed ] In 1867, Italy lost 113,000 lives; and 80,000 died of the disease in Algeria. Outbreaks in North America in the 1870s killed some 50,000 Americans as cholera spread from New Orleans to other ports along the Mississippi River and its tributaries. None of the cities had adequate sanitation systems, and cholera spread through the water supply and contact. According to A. J. Wall, the 1883–1887 part of the epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas. Cholera claimed 267,890 lives in Russia (1892); 120,000 in Spain ; 90,000 in Japan , and over 60,000 in Persia . In Egypt , cholera claimed more than 58,000 lives. The 1892 outbreak in Hamburg killed 8,600 people. Although the city government was generally held responsible for the virulence of the epidemic, it was not changed. This was the last serious European cholera outbreak, as cities improved their sanitation and water systems. [ citation needed ] From the Russian Empire, cholera most likely spread to European countries. In Russia, cholera vibrio was found in Baku in 1892. The authorities of the city, despite the mortality of the population from cholera for a long time did not recognize the outbreak of the epidemic. The residents of Baku left the city, including traveling to Astrakhan, a city located in the delta of the Volga River. After quarantine measures were introduced in Astrakhan, rumors spread among the population that living people were being put in coffins, sprinkled with lime, and buried in cholera hospitals. These rumors provoked riots. During the riots, medical workers were killed, the cholera hospital was burned down, and the infected were sent home. The incidence of the disease increased dramatically after the riots. From June 14 to September 20, 1892, more than 3% of Astrakhan's population died of cholera, with 480 cases and 316 deaths per 10,000 inhabitants. This was the demographic maximum of the 1892 cholera epidemic. An estimate of excess mortality showed an increase of 278% in June and 555% in July over the same months in 1888–1894. Of all those admitted to Astrakhan hospitals, about 73% were workers living in hostels (shelters), about 5% were workers on ships, steamships, and barges, and 12% were artisans. The social composition by estates was as follows: 1983 peasants, 316 soldiers, 262 bourgeois, 12 Cossacks, 8 nobles and 5 clergymen. Natives of Astrakhan and the province accounted for about 11% of the cases, 89% were seasonal migrants. Many children were orphaned due to the high mortality rate. Because cholera is characterized by waterborne transmission, cholera epidemics were observed in large cities along the Volga River. Much of the empire was infested with cholera vibrio. The sixth cholera pandemic , which was due to the classical strain of O1, had little effect in western Europe because of advances in sanitation and public health , but major Russian cities and the Ottoman Empire particularly suffered a high rate of cholera deaths. More than 500,000 people died of cholera in Russia from 1900 to 1925, which was a time of extreme social disruption because of revolution and warfare. The 1902–1904 cholera epidemic claimed 200,000 lives in the Philippines , including their revolutionary hero and first prime minister Apolinario Mabini . Cholera broke out 27 times during the hajj at Mecca from the 19th century to 1930. The sixth pandemic killed more than 800,000 in India . The last outbreak of cholera in the United States was in 1910–1911, when the steamship Moltke brought infected people from Naples to New York City. Vigilant health authorities isolated the infected in quarantine on Swinburne Island . Eleven people died, including a health care worker at the hospital on the island. In 1913, the Romanian Army , while invading Bulgaria during the Second Balkan War , suffered a cholera outbreak that resulted in 1,600 deaths. During the outbreak, due to cholera frequently being spread by immigrants and tourists, the disease became associated with either outsiders or marginalized groups in societies. In Italy, some blamed Jews and Romani , while in British India numerous Anglo-Indians ascribed the spread of cholera to Hindu pilgrims, and in the United States many accused Filipino immigrants of introducing the disease. As of March 2022, the World Health Organization (WHO) continues to define this outbreak as a current pandemic , noting that cholera has become endemic in many countries. In 2017, WHO announced a global strategy aimed at this pandemic with the goal of reducing cholera deaths by 90% by 2030. The seventh cholera pandemic began in Indonesia , called El Tor after the strain, and reached East Pakistan (now Bangladesh ) in 1963, India in 1964, and the Soviet Union in 1966. From South America , it spread into Italy by 1973. In the late 1970s, there were small outbreaks in Japan and in the South Pacific. There was an outbreak in Odessa in July 1970, and there were also many reports of a cholera outbreak near Baku in 1972, but information about it was suppressed in the Soviet Union. [ citation needed ] In 1970, a cholera outbreak struck the Sağmalcılar district of Istanbul , then an impoverished slum, claiming more than 50 lives. Because this incident was notorious, the district was renamed as Bayrampaşa. Also in August 1970, a few cases were reported in Jerusalem . [ citation needed ]The first cholera pandemic , though previously restricted, began in Bengal , and then spread across India by 1820. Hundreds of thousands of Indians and ten thousand British troops died during this pandemic. The cholera outbreak extended as far as China , Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea in Europe, before receding. In 1821, it is estimated that up to 100,000 deaths occurred in Korea . A second cholera pandemic reached Russia (see Cholera Riots ), Hungary (about 100,000 deaths) and Germany in 1831; it killed 130,000 people in Egypt that year. In 1832 it reached London and the United Kingdom (where more than 55,000 people died) and Paris . In London, the disease claimed 6,536 victims and came to be known as "King Cholera"; in Paris, 20,000 died (of a population of 650,000), and total deaths in France amounted to 100,000. In 1833, a cholera epidemic killed many Pomo , which are a Native American tribe. The epidemic reached Quebec , Ontario , Nova Scotia , and New York in the same year, and the Pacific coast of North America by 1834. In the center of the country [ clarification needed ] , it spread through the cities linked by the rivers and steamboat traffic. In Washington D.C. Michael Shiner , an enslaved laborer at the Washington Navy Yard recorded, "The time the colery [cholera] broke out in about June and July August and September 1832 it Raged in the City of Washington and every day they wher [were] twelve or 13 carried out to they [their] graves a day." By late July 1832, cholera had spread to Virginia and on 7 August 1832, Commodore Lewis Warrington confirmed to the Secretary of the Navy Levi Woodbury cholera was at the Gosport Navy Yard , "Between noon of that day, [1 August] and the morning of Friday [3 August], when all work on board her USS Fairchild stopped, several deaths by cholera occurred and fifteen or sixteen cases (of less violence) were reported." The epidemic of cholera, cause unknown and prognosis dire, had reached its peak. Cholera afflicted Mexico's populations in 1833 and 1850, prompting officials to quarantine some populations and fumigate buildings, particularly in major urban centers, but nonetheless the epidemics were disastrous. During this pandemic, the scientific community varied in its beliefs about the causes of cholera. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious, although doctors did not understand how it spread. The United States believed that cholera was brought by recent immigrants, specifically the Irish, and epidemiologists understand they were carrying disease from British ports. Lastly, some British thought the disease might rise from divine intervention. The social importance of the government having a direct role in the development and application of science was demonstrated through the U.S. government's support of efforts to control the epidemic. The third cholera pandemic deeply affected Russia, with over one million deaths. Over 15,000 people died of cholera in Mecca in 1846. A two-year outbreak began in England and Wales in 1848, and claimed 52,000 lives. In 1849, a second major outbreak occurred in France. In London, it was the worst outbreak in the city's history, claiming 14,137 lives, over twice as many as the 1832 outbreak. Cholera hit Ireland in 1849 and killed many of the Irish Famine survivors, already weakened by starvation and fever. In 1849, cholera claimed 5,308 lives in the major port city of Liverpool , England , an embarkation point for immigrants to North America, and 1,834 in Hull , England. In Vietnam and Cambodia, cholera hit in summer 1849, killing approximately 589,000 to 800,000 people within one year, along with its consequential famine. An outbreak in North America took the life of former U.S. President James K. Polk . Cholera, believed spread from Irish immigrant ships from England, spread throughout the Mississippi river system , killing over 4,500 in St. Louis and over 3,000 in New Orleans . Thousands died in New York , a major destination for Irish immigrants. Cholera claimed 200,000 victims in Mexico . That year, cholera was transmitted along the California , Mormon , and Oregon Trails as 6,000 to 12,000 are believed to have died on their way to the California Gold Rush , Utah and Oregon in the cholera years of 1849–1855. It is believed more than 150,000 Americans died during the two pandemics between 1832 and 1849. In 1851, a ship coming from Cuba carried the disease to Gran Canaria . It is considered that more than 6,000 people died in the island during summer, out of a population of 58,000. In 1852, cholera spread east to the Dutch East Indies and later was carried to Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal contributed to transmission of the disease by travelers and troops to Iran , Iraq , Arabia , and Russia. Japan suffered at least seven major outbreaks of cholera between 1858 and 1902. Between 100,000 and 200,000 people died of cholera in Tokyo in an outbreak in 1858–1860. In 1854, an outbreak of cholera in Chicago took the lives of 5.5 percent of the population (about 3,500 people). Providence, Rhode Island , suffered an outbreak so widespread that for the next thirty years, 1854 was known there as "The Year of Cholera." In 1853–1854, London's epidemic claimed 10,739 lives. The 1854 Broad Street Cholera outbreak in London ended after the physician John Snow identified a neighborhood Broad Street pump as contaminated and convinced officials to remove its handle to prevent people from drawing water there. His study proved contaminated water was the main agent spreading cholera, although he did not identify the contaminant. It would take many years for this message to be believed and fully acted upon. In Spain , over 236,000 died of cholera in the epidemic of 1854–1855. The disease reached South America in 1854 and 1855, with victims in Venezuela and Brazil. During the third pandemic, residents of Tunisia , which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. Some United States scientists began to believe that cholera was somehow associated with African Americans, as the disease was prevalent in the South in areas of black populations. Current researchers note their populations were underserved in terms of sanitation infrastructure and health care, and they lived near the waterways by which travelers and ships carried the disease. From November 10, 1855, to December 1856, the disease spread through Puerto Rico, claiming 25,820 victims. Cemeteries were expanded to allow for the burial of victims of cholera. In Arecibo , a large municipality of Puerto Rico, the number of people dying in the streets was so great that the city could not keep up. A man named Ulanga made it his responsibility to collect and carry the dead to the provisional Cementerio de los Coléricos . The fourth cholera pandemic of the century began in the Ganges Delta of the Bengal region and traveled with Muslim pilgrims to Mecca . In its first year, the epidemic claimed 30,000 of 90,000 Mecca pilgrims. Cholera spread throughout the Middle East and was carried to Russia, Europe, Africa and North America, in each case spreading from port cities and along inland waterways. [ citation needed ] The pandemic reached Northern Africa in 1865 and spread to sub-Saharan Africa, killing 70,000 in Zanzibar in 1869–1870. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have taken 165,000 lives in the Austrian Empire , including 30,000 each in Hungary and Belgium and 20,000 in the Netherlands. Other deaths from cholera at the time included 115,000 in Germany, 90,000 in Russia, and 30,000 in Belgium. In London in June 1866, a localized epidemic in the East End claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems (see London sewerage system ); the East End section was not quite complete. Epidemiologist William Farr identified the East London Water Company as the source of the contamination. Farr made use of prior work by John Snow and others pointing to contaminated drinking water as the likely cause of cholera in an 1854 outbreak . Quick action prevented further deaths. In the same year, the use of contaminated canal water in local water works caused a minor outbreak at Ystalyfera in South Wales. Workers associated with the company and their families were most affected, and 119 died. [ citation needed ] In 1867, Italy lost 113,000 lives; and 80,000 died of the disease in Algeria. Outbreaks in North America in the 1870s killed some 50,000 Americans as cholera spread from New Orleans to other ports along the Mississippi River and its tributaries. None of the cities had adequate sanitation systems, and cholera spread through the water supply and contact. According to A. J. Wall, the 1883–1887 part of the epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas. Cholera claimed 267,890 lives in Russia (1892); 120,000 in Spain ; 90,000 in Japan , and over 60,000 in Persia . In Egypt , cholera claimed more than 58,000 lives. The 1892 outbreak in Hamburg killed 8,600 people. Although the city government was generally held responsible for the virulence of the epidemic, it was not changed. This was the last serious European cholera outbreak, as cities improved their sanitation and water systems. [ citation needed ] From the Russian Empire, cholera most likely spread to European countries. In Russia, cholera vibrio was found in Baku in 1892. The authorities of the city, despite the mortality of the population from cholera for a long time did not recognize the outbreak of the epidemic. The residents of Baku left the city, including traveling to Astrakhan, a city located in the delta of the Volga River. After quarantine measures were introduced in Astrakhan, rumors spread among the population that living people were being put in coffins, sprinkled with lime, and buried in cholera hospitals. These rumors provoked riots. During the riots, medical workers were killed, the cholera hospital was burned down, and the infected were sent home. The incidence of the disease increased dramatically after the riots. From June 14 to September 20, 1892, more than 3% of Astrakhan's population died of cholera, with 480 cases and 316 deaths per 10,000 inhabitants. This was the demographic maximum of the 1892 cholera epidemic. An estimate of excess mortality showed an increase of 278% in June and 555% in July over the same months in 1888–1894. Of all those admitted to Astrakhan hospitals, about 73% were workers living in hostels (shelters), about 5% were workers on ships, steamships, and barges, and 12% were artisans. The social composition by estates was as follows: 1983 peasants, 316 soldiers, 262 bourgeois, 12 Cossacks, 8 nobles and 5 clergymen. Natives of Astrakhan and the province accounted for about 11% of the cases, 89% were seasonal migrants. Many children were orphaned due to the high mortality rate. Because cholera is characterized by waterborne transmission, cholera epidemics were observed in large cities along the Volga River. Much of the empire was infested with cholera vibrio. The sixth cholera pandemic , which was due to the classical strain of O1, had little effect in western Europe because of advances in sanitation and public health , but major Russian cities and the Ottoman Empire particularly suffered a high rate of cholera deaths. More than 500,000 people died of cholera in Russia from 1900 to 1925, which was a time of extreme social disruption because of revolution and warfare. The 1902–1904 cholera epidemic claimed 200,000 lives in the Philippines , including their revolutionary hero and first prime minister Apolinario Mabini . Cholera broke out 27 times during the hajj at Mecca from the 19th century to 1930. The sixth pandemic killed more than 800,000 in India . The last outbreak of cholera in the United States was in 1910–1911, when the steamship Moltke brought infected people from Naples to New York City. Vigilant health authorities isolated the infected in quarantine on Swinburne Island . Eleven people died, including a health care worker at the hospital on the island. In 1913, the Romanian Army , while invading Bulgaria during the Second Balkan War , suffered a cholera outbreak that resulted in 1,600 deaths. During the outbreak, due to cholera frequently being spread by immigrants and tourists, the disease became associated with either outsiders or marginalized groups in societies. In Italy, some blamed Jews and Romani , while in British India numerous Anglo-Indians ascribed the spread of cholera to Hindu pilgrims, and in the United States many accused Filipino immigrants of introducing the disease. As of March 2022, the World Health Organization (WHO) continues to define this outbreak as a current pandemic , noting that cholera has become endemic in many countries. In 2017, WHO announced a global strategy aimed at this pandemic with the goal of reducing cholera deaths by 90% by 2030. The seventh cholera pandemic began in Indonesia , called El Tor after the strain, and reached East Pakistan (now Bangladesh ) in 1963, India in 1964, and the Soviet Union in 1966. From South America , it spread into Italy by 1973. In the late 1970s, there were small outbreaks in Japan and in the South Pacific. There was an outbreak in Odessa in July 1970, and there were also many reports of a cholera outbreak near Baku in 1972, but information about it was suppressed in the Soviet Union. [ citation needed ] In 1970, a cholera outbreak struck the Sağmalcılar district of Istanbul , then an impoverished slum, claiming more than 50 lives. Because this incident was notorious, the district was renamed as Bayrampaşa. Also in August 1970, a few cases were reported in Jerusalem . [ citation needed ]Vibrio cholerae has shown to be a very potent pathogenic bacterium causing many pandemics and epidemics over the past three centuries. However, most outbreaks are known to be self-limiting, meaning they come to an end after peaking, without human intervention. One of the mechanisms significantly determining the course of epidemics is phage predation. This process is strongly dependent on successful recognition of the bacteria by lytic phages, in which cell surface receptors play a crucial role. Bacteria can reduce their susceptibility by changing their surface receptors and preventing phage adsorption. In the case of V. cholerae , the changed receptor gene expression is due to an alteration in cell-density during its infection cycle, a process called quorum sensing (QS). The stool samples collected from patients contain clumps of bacterial cells, demonstrating the occurrence of cell-cell interaction in the latter stage of the infection cycle. QS is strongly regulated by two auto-inducer molecules, AI-2 and CAI-1. Evidently, these molecules will have a significant effect on the success of phage predation in V. cholerae infections. [ citation needed ] A previous study has unravelled the mode of action of auto-inducers on preventing predation on the level of phage entry. The study has shown that the aforementioned auto-inducers downregulate the ten biosynthetic genes of the surface O-antigen, which is primarily used as a phage receptor for Vibriophages. This mechanism results in an increased phage resistance. It can be stated that the loss of the ability to produce the receptor, reduces the possibility of a phage-dependent limitation or even elimination of V. cholerae . This should be kept in mind when developing a treatment for enteric bacterial infections with phages as an intervention tool. Future approaches may include additional quorum regulators that operate as "quorum quenchers" to reduce quorum-mediated phage resistance. [ citation needed ] In 1992 a new strain appeared in Asia, a non-O1, nonagglutinable vibrio (NAG), which was named O139 Bengal. It was first identified in Tamil Nadu , India, and for a while displaced El Tor in southern Asia. It decreased in prevalence from 1995 to around 10 percent of all cases. It is considered to be an intermediate between El Tor and the classic strain, and occurs in a new serogroup. Scientists warn of evidence of wide-spectrum resistance by cholera bacteria to drugs such as trimethoprim , sulfamethoxazole and streptomycin . [ citation needed ]In 1992 a new strain appeared in Asia, a non-O1, nonagglutinable vibrio (NAG), which was named O139 Bengal. It was first identified in Tamil Nadu , India, and for a while displaced El Tor in southern Asia. It decreased in prevalence from 1995 to around 10 percent of all cases. It is considered to be an intermediate between El Tor and the classic strain, and occurs in a new serogroup. Scientists warn of evidence of wide-spectrum resistance by cholera bacteria to drugs such as trimethoprim , sulfamethoxazole and streptomycin . [ citation needed ]A persistent urban myth states 90,000 people died in Chicago of cholera and typhoid fever in 1885, but this story has no factual basis. In 1885, a torrential rainstorm flushed the Chicago River and its attendant pollutants into Lake Michigan far enough that the city's water supply was contaminated. But, as cholera was not present in the city, there were no cholera-related deaths. As a result of the pollution, the city made changes to improve its treatment of sewage and avoid similar events. [ citation needed ]Unlike tuberculosis ("consumption"), which in literature and the arts was often romanticized as a disease of denizens of the demimondaine or those with an artistic temperament, cholera is a disease that today almost entirely affects the lower-classes living in filth and poverty. This, and the unpleasant course of the disease – which includes voluminous "rice-water" diarrhea, the hemorrhaging of liquids from the mouth, and violent muscle contractions which continue even after death – has discouraged the disease being romanticized. It is seldom presented at all in popular culture.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2010s_Haiti_cholera_outbreak/html

2010s Haiti cholera outbreak

Cases: 819,790 (Haiti) 33,342 (DR) 678 (Cuba) 190 (Mexico) Cases recorded in: The 2010s Haiti cholera outbreak was the first modern large-scale outbreak of cholera —a disease once considered beaten back largely due to the invention of modern sanitation . The disease was reintroduced to Haiti in October 2010, not long after the disastrous earthquake earlier that year, and since then cholera has spread across the country and become endemic , causing high levels of both morbidity and mortality . Nearly 800,000 Haitians have been infected by cholera, and more than 9,000 have died, according to the United Nations (UN). Cholera transmission in Haiti today [ when? ] is largely a function of eradication efforts including WASH (water, sanitation, and hygiene), education, oral vaccination, and climate variability. Early efforts were made to cover up the source of the epidemic, but thanks largely to the investigations of journalist Jonathan M. Katz and epidemiologist Renaud Piarroux , it is widely believed to be the result of contamination by infected United Nations peacekeepers deployed from Nepal . In terms of total infections, the outbreak has since been surpassed by the war-fueled 2016–2021 Yemen cholera outbreak , although the Haiti outbreak is still one of the most deadly modern outbreaks. After a three-year hiatus, new cholera cases reappeared in October 2022. In January 2010, a 7.0 magnitude earthquake hit Haiti, killing over 200,000 people and further disrupting healthcare and sanitation infrastructure in the country. In the aftermath of the earthquake, international workers from many countries arrived in Haiti to assist in the response and recovery efforts, including a number of workers from countries where cholera is endemic . Before the outbreak, no cases of cholera had been identified in Haiti for more than a century, and the Caribbean region as a whole had not been affected by the cholera outbreak originating in Peru in 1991. The population's lack of prior exposure and acquired immunity contributed to the severity of the outbreak. Cholera is caused by the bacterium Vibrio cholerae that when ingested can cause diarrhea and vomiting within several hours to 2–3 days. Without proper treatment including oral rehydration, cholera can be fatal. The suspected source of Vibrio cholerae in Haiti was the Artibonite River , from which most of the affected people had consumed the water. Each year, tens of thousands of Haitians bathe, wash their clothes and dishes, obtain drinking water, and recreate in this river, therefore resulting in high rates of exposure to Vibrio cholerae . The cholera outbreak began nine months after January 2010 earthquake, leading some observers to wrongly suspect it was a result of the natural disaster. However, Haitians grew immediately suspicious of a UN peacekeeper base, home to Nepalese peacekeepers, positioned on a tributary of the Artibonite River. Neighboring farmers reported an undeniable stench of human feces coming from the base, to the extent that local Haitians began getting their drinking water upstream from the base. In response, United Nations Stabilization Mission in Haiti ( MINUSTAH ) officials issued a press statement denying the possibility that the base could have caused the epidemic, citing stringent sanitation standards. The next day, 27 October 2010, Jonathan M. Katz , an Associated Press correspondent, visited the base and found gross inconsistencies between the statement and the base's actual conditions. Katz also happened upon UN military police taking samples of ground water to test for cholera, despite UN assertions that it was not concerned about a possible link between its peacekeepers and the disease. Neighbors told the reporter that waste from the base often spilled into the river. Later that day, a crew from Al Jazeera English , including reporter Sebastian Walker , filmed the soldiers trying to excavate a leaking pipe; the video was posted online the following day and, citing the AP report, drew increased awareness to the base. MINUSTAH spokesmen later contended that the samples taken from the base proved negative for cholera. However, an AP investigation showed that the tests were improperly done at a laboratory in the Dominican Republic , which had no prior experience of testing for cholera. For three months, UN officials, the U.S. Centers for Disease Control and Prevention (CDC), and others argued against investigating the source of the outbreak. Gregory Hartl, a spokesman for the World Health Organization (WHO), said finding the cause of the outbreak was "not important". Hartl said, "Right now, there is no active investigation. I cannot say one way or another [if there will be]. It is not something we are thinking about at the moment. What we are thinking about is the public health response in Haiti." Jordan Tappero, the lead epidemiologist at the CDC, said the main task was to control the outbreak, not to look for the source of the bacteria and that "we may never know the actual origin of this cholera strain." A CDC spokesperson, Kathryn Harben, added that "at some point in the future, when many different analyses of the strain are complete, it may be possible to identify the origin of the strain causing the outbreak in Haiti." Paul Farmer , co-founder of the medical organization Partners In Health , and a UN official himself who served Bill Clinton 's deputy at the Office of the Special Envoy for Haiti , told the AP's Katz on 3 November 2010 that there was no reason to wait. Farmer stated, "The idea that we'd never know is not very likely. There's got to be a way to know the truth without pointing fingers." A cholera expert, John Mekalanos, supported the assertion that it was important to know where and how the disease emerged because the strain is a "novel, virulent strain previously unknown in the Western Hemisphere and health officials need to know how it spreads." Some US professors have disagreed with the contention that Nepalese soldiers caused the outbreak. Some said it was more likely dormant cholera bacteria had been aroused by various environmental incidents in Haiti. Before studying the case, they said a sequence of events, including changes in climate triggered by the La Niña climate pattern and unsanitary living conditions for those affected by the earthquake, triggered bacteria already present in the water and soil to multiply and infect humans. However, a study unveiled in December and conducted by French epidemiologist Renaud Piarroux contended that UN troops from Nepal, rather than environmental factors, had started the epidemic as waste from outhouses at their base flowed into and contaminated the Artibonite River. A separate study published in December in the New England Journal of Medicine presented DNA sequence data for the Haitian cholera isolate, finding that it was most closely related to a cholera strain found in Bangladesh in 2002 and 2008. It was more distantly related to existing South American strains of cholera, the authors reported, adding that "the Haitian epidemic is probably the result of the introduction, through human activity, of a V. cholerae strain from a distant geographic source." Under intense pressure, the UN relented, and said it would appoint a panel to investigate the source of the cholera strain. That panel's report, issued in May 2011, confirmed substantial evidence that the Nepalese troops had brought the disease to Haiti. The U.S. Centers for Disease Control and Prevention (CDC) utilized DNA fingerprinting to tests various samples of cholera from Haitian patients to pinpoint the specific strain of cholera found in Haiti. During an epidemiological outbreak investigation, DNA fingerprinting of bacteria can be extremely helpful in identifying the source of an outbreak. The results of the CDC tests showed that the specific strain of cholera found in samples taken from Haitian patients was Vibrio cholerae serogroup O1, serotype Ogawa, a strain found in South Asia. This specific strain of cholera is endemic in Nepal, therefore supporting the Haitian suspicion that Nepalese peacekeepers were the source of the outbreak. However, in the report's concluding remarks, the authors stated that a "confluence of circumstances" was to blame. Rita Colwell , former director of the National Science Foundation and climate change expert, still contends that climate changes were an important factor in cholera's spread, stating in an interview with UNEARTH News in August 2013 that the outbreak was "triggered by a complicated set of factors. The precipitation and temperatures were above average during 2010 and that, in conjunction with a destroyed water and sanitation infrastructure, can be considered to have contributed to this major disease outbreak." In August 2016, after Katz obtained a leaked copy of a report by United Nations Special Rapporteur Philip Alston , Secretary General of the United Nations Ban Ki-moon accepted responsibility for the UN's role in the initial outbreak and stated that a "significant new set of U.N. actions" will be required to help solve the problem. In 2017, Katz also revealed the existence of emails that showed that "officials at the highest levels of the U.S. government were aware almost immediately that U.N. forces likely played a role in the outbreak". Katz reported that these emails showed "multiple federal agencies, from national security officials to scientists on the front lines, shielded the United Nations from accountability to protect the organization and themselves". At the beginning of the outbreak, widespread panic regarding the virulence of the disease and the UN's denial of the blame caused increased tension between the UN and the Haitian community. On 15 November 2010, a riot broke out in Cap-Haïtien following the death of a young Haitian inside the Cap-Haïtien UN base and rumours that the outbreak was caused by UN soldiers from Nepal. Protesters demanded that the Nepalese brigade of the UN leave the country. At least five people were killed in the riots, including one UN personnel. Riots then continued for a second day. Following the riots, the UN continued their position that the Nepalese soldiers were not to blame, and rather said that the riots was being staged for "political reasons because of forthcoming elections", as the Haitian government sent its own forces to "protest" the UN peacekeepers. According to one author, rather than confront the inescapable conclusion that the UN was indeed the cause, "the world's preeminent humanitarian organization continued to dissemble ." During a third day of riots, UN personnel were blamed for shooting at least five protestors, but denied responsibility. On the fourth day of demonstrations against the UN presence, police fired tear gas into an IDP camp in the capital. The outbreak of cholera became an issue for Haitian candidates to answer in the 2010 general election . There were fears that the election could be postponed. The head of MINUSTAH , Edmond Mulet said that it should not be delayed as that could lead to a political vacuum with untold potential problems. In November 2011, the UN received a petition from 5,000 victims for hundreds of millions of dollars in reparations over the outbreak thought to have been caused by UN members of MINUSTAH. In February 2013, the United Nations responded by invoking its immunity from lawsuits under the Convention on the Privileges and Immunities of the United Nations . On 9 October 2013, Bureau des Avocats Internationaux (BAI), the Institute for Justice & Democracy in Haiti (IJDH), and civil rights lawyer Ira Kurzban's law firm Kurzban Kurzban Weinger Tetzeli & Pratt, P.A.(KKWT) filed a lawsuit against the UN in the Southern District of New York . The lawsuit was dismissed, but an appeal was filed in the Second Circuit . In October 2016, the Second Circuit Court of Appeals upheld the United Nations' immunity from claims. On 11 March 2014, a second lawsuit was filed, Laventure v. United Nations , in the Eastern District of New York, on behalf of more than 1,500 victims of the disaster. In an opinion piece in the Wall Street Journal, an attorney for the plaintiffs wrote: "Imagine if the United Nations killed thousands on the streets of New York. Or London. Or Paris. And sickened nearly a million more. Would the U.N. claim it was not liable? Of course not. The international community wouldn't allow it." A lead lawyer for the plaintiffs also noted that the lawsuit was different from the one filed by the IDJH, in that it alleged that liability had been accepted by the U.N. in the 1990s. The lawyer stated that immunity: "should not be a shield to hide behind because the United Nations (or the U.S. government) doesn't like the price tag that comes with the U.N.'s indisputable gross negligence in this case." This case, too, was dismissed by the U.S. District Court, and the Court of Appeals. The appeal is currently before the United States Supreme Court . In December 2016, the then UN Secretary-General Ban Ki-moon finally apologized on behalf of UN, saying he was "profoundly sorry" for the outbreak. The Secretary-General promised to spend $400 million to aid the victims and to improve the nation's crumbling sanitation and water systems. As of March 2017, the UN has come through with only 2 percent of that amount. On 21 October 2010, the Haitian Ministry of Public Health and Population (MSPP) confirmed the first case of cholera in Haiti in over a century. The outbreak began in the rural Center department of Haiti , about 100 kilometres (62 mi) north of the capital, Port-au-Prince . By the first 10 weeks of the epidemic, cholera spread to all of Haiti's 10 departments or provinces. It had killed 4,672 people by March 2011 and hospitalized thousands more. The outbreak in Haiti was the most severe in recent history prior to 2010; the World Health Organization reported that from 2010 to 2011, the outbreak in Haiti accounted for 57% of all cases and 45% of all deaths from cholera worldwide. By January 2013, more than 6% of Haitians acquired the disease. The highest incidence of cholera occurred in 2011 immediately following the introduction of the primary exposure. The rate of incidence slowly declined thereafter, with spikes resulting from rainy seasons and hurricanes. As reported by the Haitian Health Ministry, as of August 2012, the outbreak had caused 586,625 cholera cases and 7,490 deaths. According to the Pan American Health Organization , as of 21 November 2013, there had been 689,448 cholera cases in Haiti, leading to 8,448 deaths. While there had been an apparent lull in cases in 2014, by August 2015 the rainy season brought a spike in the number of cases. At that time more than 700,000 Haitians had become ill with the disease and the death toll had climbed to 9,000. As of March 2017, around 7% of Haiti's population (around 800,665 people) have been affected with cholera, and 9,480 Haitians have died. Latest epidemiological report by WHO in 2018 indicate a total of 812,586 cases of cholera in Haiti since October 2010, resulting in 9,606 deaths. However, a 2011 serological survey indicated that a large number of patients may have not been diagnosed: while only 18% of over a 2,500 respondents in a rural commune reported a cholera diagnosis, 64% had antibodies against it. The first case of cholera was reported in the Dominican Republic in mid-November 2010, following the Pan-America Health Organization's prediction. By January 2011, the Dominican Republic had reported 244 cases of cholera. The first man to die of it there died in the province of Altagracia on 23 January 2011. The Dominican Republic was particularly vulnerable to exposure of cholera due to sharing a border with Haiti, and a large Haitian refugee population displaced following the 2010 earthquake. As of the latest epidemiological report by WHO in 2018, there has been a total of 33,188 cases of cholera in the Dominican Republic resulting in 504 deaths. In late January 2011, more than 20 Venezuelans were reported to have been taken to hospital after contracting cholera after visiting the Dominican Republic. 37 cases were reported in total. Contaminated food was blamed for the spread of the disease. Venezuelan health minister Eugenia Sader gave a news conference which was broadcast on VTV during which she described all 37 people as "doing well". The minister had previously observed that the last time cholera was recorded in Venezuela was twenty years before this, in 1991. In late June 2012, Cuba confirmed three deaths and 53 cases of cholera in Manzanillo ; in 2013 there were 51 cases of cholera reported in Havana . Vaccination of half the population was urged by the University of Florida to stem the epidemic. On 21 October 2010, the Haitian Ministry of Public Health and Population (MSPP) confirmed the first case of cholera in Haiti in over a century. The outbreak began in the rural Center department of Haiti , about 100 kilometres (62 mi) north of the capital, Port-au-Prince . By the first 10 weeks of the epidemic, cholera spread to all of Haiti's 10 departments or provinces. It had killed 4,672 people by March 2011 and hospitalized thousands more. The outbreak in Haiti was the most severe in recent history prior to 2010; the World Health Organization reported that from 2010 to 2011, the outbreak in Haiti accounted for 57% of all cases and 45% of all deaths from cholera worldwide. By January 2013, more than 6% of Haitians acquired the disease. The highest incidence of cholera occurred in 2011 immediately following the introduction of the primary exposure. The rate of incidence slowly declined thereafter, with spikes resulting from rainy seasons and hurricanes. As reported by the Haitian Health Ministry, as of August 2012, the outbreak had caused 586,625 cholera cases and 7,490 deaths. According to the Pan American Health Organization , as of 21 November 2013, there had been 689,448 cholera cases in Haiti, leading to 8,448 deaths. While there had been an apparent lull in cases in 2014, by August 2015 the rainy season brought a spike in the number of cases. At that time more than 700,000 Haitians had become ill with the disease and the death toll had climbed to 9,000. As of March 2017, around 7% of Haiti's population (around 800,665 people) have been affected with cholera, and 9,480 Haitians have died. Latest epidemiological report by WHO in 2018 indicate a total of 812,586 cases of cholera in Haiti since October 2010, resulting in 9,606 deaths. However, a 2011 serological survey indicated that a large number of patients may have not been diagnosed: while only 18% of over a 2,500 respondents in a rural commune reported a cholera diagnosis, 64% had antibodies against it. The first case of cholera was reported in the Dominican Republic in mid-November 2010, following the Pan-America Health Organization's prediction. By January 2011, the Dominican Republic had reported 244 cases of cholera. The first man to die of it there died in the province of Altagracia on 23 January 2011. The Dominican Republic was particularly vulnerable to exposure of cholera due to sharing a border with Haiti, and a large Haitian refugee population displaced following the 2010 earthquake. As of the latest epidemiological report by WHO in 2018, there has been a total of 33,188 cases of cholera in the Dominican Republic resulting in 504 deaths. In late January 2011, more than 20 Venezuelans were reported to have been taken to hospital after contracting cholera after visiting the Dominican Republic. 37 cases were reported in total. Contaminated food was blamed for the spread of the disease. Venezuelan health minister Eugenia Sader gave a news conference which was broadcast on VTV during which she described all 37 people as "doing well". The minister had previously observed that the last time cholera was recorded in Venezuela was twenty years before this, in 1991. In late June 2012, Cuba confirmed three deaths and 53 cases of cholera in Manzanillo ; in 2013 there were 51 cases of cholera reported in Havana . Vaccination of half the population was urged by the University of Florida to stem the epidemic. Before the outbreak, Haiti suffered from relatively poor public health and sanitation infrastructure. In 2002, Haiti was ranked 147th out of 147 countries for water security . As of 2008, 37% of Haiti's population lacked access to adequate drinking water, and 83% lacked improved sanitation facilities. As such, families often obtain their water from natural sources, such as rivers, that may be contaminated with V. cholerae. Poor sanitation infrastructure allows cholera bacterium to enter these waterways. Persons are subsequently infected via the fecal-oral route when the water is used for drinking and cooking, and poor hygiene often contributes to the spread of cholera through the household or community. There is also a chronic shortage of health care personnel, and hospitals lack adequate resources to treat those infected with cholera ‍ — a situation that became readily apparent after January 2010 earthquake. Insufficient water and sanitation infrastructure, coupled with a massive earthquake in 2010, made Haiti particularly vulnerable to an outbreak of waterborne disease. Malnutrition of the population, another pre-existing condition that was exacerbated by the earthquake, may have also contributed to the severity of the outbreak. Research from previous outbreaks shows that duration of diarrhea can be prolonged by up to 70% in individuals suffering from severe malnutrition. Furthermore, Haitians had no biological immunity to the strain of cholera introduced since they had no previous exposure to it. Therefore, physiological factors including malnutrition and lack of immunity may have allowed cholera to spread rapidly throughout the country. Lack of information and limited access to some rural areas can also be a barrier to care. Some aid agencies have reported that mortality and morbidity tolls may be higher than the official figures because the government does not track deaths in rural areas where people never reached a hospital or emergency treatment center. Limitations in the data from Haiti stem from a lack of pre-outbreak lack of surveillance infrastructure and laboratories to properly test samples and diagnose cases. Haiti was tasked with developing surveillance systems and laboratories after the 2010 earthquake and cholera outbreak which caused difficulties tracking the progression and scale of the outbreak. Because of the lack of established surveillance, much of the case report data is anecdotal and potentially underestimated. Also, because of lack of laboratory confirmation for the vast majority of cases of cholera, it is possible that other diarrheal diseases were being falsely classified as cholera. Rainy seasons and hurricanes continue to cause a temporary spike in incident cases and deaths. Moreover, as a result of global warming and climate change, Haiti is at an increased risk of cholera transmission. The Intergovernmental Panel on Climate Change (IPCC) advances that global warming between 1.5–2 degrees Celsius will very likely lead to an increase in frequency and intensity of natural disasters and extreme weather events. Resource-poor countries are poised to be affected more so than more developed and economically secure countries. Environmental factors such as temperature increases, severe weather events, and natural disasters have a two-fold impact on the transmission potential of cholera in Haiti: 1) they present conditions favorable to the persistence and growth of V. cholerae in the environment, and 2) they devastate a country's infrastructure and strain public health and health care resources. An exhaustive study into environmental factors influencing the spread of cholera in Haiti cites above average air temperatures following the earthquake, "anomalously high rainfall" from September to October 2010, and damage to the limited water and sanitation infrastructure as likely converging to create conditions favorable to a cholera outbreak. Before the outbreak, Haiti suffered from relatively poor public health and sanitation infrastructure. In 2002, Haiti was ranked 147th out of 147 countries for water security . As of 2008, 37% of Haiti's population lacked access to adequate drinking water, and 83% lacked improved sanitation facilities. As such, families often obtain their water from natural sources, such as rivers, that may be contaminated with V. cholerae. Poor sanitation infrastructure allows cholera bacterium to enter these waterways. Persons are subsequently infected via the fecal-oral route when the water is used for drinking and cooking, and poor hygiene often contributes to the spread of cholera through the household or community. There is also a chronic shortage of health care personnel, and hospitals lack adequate resources to treat those infected with cholera ‍ — a situation that became readily apparent after January 2010 earthquake. Insufficient water and sanitation infrastructure, coupled with a massive earthquake in 2010, made Haiti particularly vulnerable to an outbreak of waterborne disease. Malnutrition of the population, another pre-existing condition that was exacerbated by the earthquake, may have also contributed to the severity of the outbreak. Research from previous outbreaks shows that duration of diarrhea can be prolonged by up to 70% in individuals suffering from severe malnutrition. Furthermore, Haitians had no biological immunity to the strain of cholera introduced since they had no previous exposure to it. Therefore, physiological factors including malnutrition and lack of immunity may have allowed cholera to spread rapidly throughout the country. Lack of information and limited access to some rural areas can also be a barrier to care. Some aid agencies have reported that mortality and morbidity tolls may be higher than the official figures because the government does not track deaths in rural areas where people never reached a hospital or emergency treatment center. Limitations in the data from Haiti stem from a lack of pre-outbreak lack of surveillance infrastructure and laboratories to properly test samples and diagnose cases. Haiti was tasked with developing surveillance systems and laboratories after the 2010 earthquake and cholera outbreak which caused difficulties tracking the progression and scale of the outbreak. Because of the lack of established surveillance, much of the case report data is anecdotal and potentially underestimated. Also, because of lack of laboratory confirmation for the vast majority of cases of cholera, it is possible that other diarrheal diseases were being falsely classified as cholera. Rainy seasons and hurricanes continue to cause a temporary spike in incident cases and deaths. Moreover, as a result of global warming and climate change, Haiti is at an increased risk of cholera transmission. The Intergovernmental Panel on Climate Change (IPCC) advances that global warming between 1.5–2 degrees Celsius will very likely lead to an increase in frequency and intensity of natural disasters and extreme weather events. Resource-poor countries are poised to be affected more so than more developed and economically secure countries. Environmental factors such as temperature increases, severe weather events, and natural disasters have a two-fold impact on the transmission potential of cholera in Haiti: 1) they present conditions favorable to the persistence and growth of V. cholerae in the environment, and 2) they devastate a country's infrastructure and strain public health and health care resources. An exhaustive study into environmental factors influencing the spread of cholera in Haiti cites above average air temperatures following the earthquake, "anomalously high rainfall" from September to October 2010, and damage to the limited water and sanitation infrastructure as likely converging to create conditions favorable to a cholera outbreak. Hundreds of thousands of dollars have been dedicated towards eradicating cholera in Haiti since its introduction in 2010, yet unsanitary conditions and climate-driven forces allow cholera transmission to continue. While the number of new cases of cholera has drastically decreased from 2010, and is currently the lowest it has been since the outbreak began, the incidence remains at 25.5 per 100,000 population as of October 2018 . Over time, there has been significant progress in the reduction of caseloads and overall number of deaths. According to one PAHO/WHO report, "the cumulative case-fatality rate (CFR) has remained around 1% since 2011". These achievements can be contributed to intensified international and local medical efforts and an increased emphasis on preventative measures, including improved sanitation, such as latrines, and changes in Haitian behaviors such as treating water, thoroughly cooking food, and rigorous hand-washing. Despite these progresses, cholera remains endemic in Haiti, and further resources are needed to fully eradicate it. After former UN Secretary General Ban Ki Moon accepted UN responsibility for the introduction of cholera in Haiti in December 2016, Moon projected a necessary $400 million in funding over two years in order to fully eradicate cholera in Haiti. The Government of Haiti has dedicated itself to the complete eradication of cholera from Haiti by 2022 as presented in the Cholera Elimination Plan (PNEC) 2013 – 2022. UN Secretary-General António Guterres , successor to Ban Ki-moon , took up Ban's commitment to assist Haiti in the eradication of cholera when he took office on 31 December 2016, as demonstrated by strategic objective 2 of the 2017– 2018 Haiti Revised Humanitarian Plan. Strategic objective 2 reads, "Save lives from epidemics – Reduce mortality and morbidity due to cholera outbreaks and other waterborne diseases through the reduction of vulnerability, strengthening of epidemiological surveillance and ensuring of rapid and effective response". The 2017 – 2018 Haiti Revised Humanitarian Plan identifies 1.9 million people in need of assistance for the protection from cholera, of which, 1.5 million people are targeted through programming totaling US$21.7 million. Currently, the UN and Government of Haiti are on target to reach the 2016 – 2018 midterm goal to reduce the incidence of cholera to less than 0.1% by the end of 2018. However, any disruption in funding of support services may result in a spike in transmission and the interruption of the downward trend. The first challenge to the eradication of cholera in Haiti is the country's vulnerability to disasters, putting it in a state of protracted crises. The climax of cholera incidence in Haiti was in 2011 with 352,000 new cases following the introduction of cholera in Haiti in late 2010. Incidence rates gradually declined until 2016 when there was another spike in the transmission and incidence of cholera following Hurricane Matthew's destruction in Haiti from 2–5 October 2016. There was a rise in cholera incidence from 32,000 new cases in 2015 to 42,000 new cases in 2016. By re-damaging Haiti's fragile water and sanitation infrastructure, Hurricane Matthew allowed cholera to rear its head. These figures demonstrate that the fight against cholera in Haiti, while improving, is on unstable ground. This indicates that while eradication efforts have largely been focused on vaccination and community education to prevent transmission, and oral rehydration to reduce mortality, the underlying vulnerabilities that perpetuate the disaster remain, particularly insufficient and unequal access to improved water and sanitation. While the Government of Haiti's Cholera Elimination Plan (PNEC) 2013 – 2022 and the New UN System Approach on Cholera in Haiti (see solutions below for more information) lay out plans for the elimination of cholera in Haiti by 2022, these are entirely dependent on funding. In former Secretary General Moon's 5 December 2016 remarks he says, "Without political will and financial support from the membership of the United Nations, we have only good intentions and words. Words are powerful – but they cannot replace action and material support". Due to the infectious nature of cholera, any lapse in funding for programming will likely result in setbacks in elimination. As of 2017, funding for cholera is at risk due to increasing food insecurity and shelter needs for Haitian refugees returning from the Dominican Republic. In the 2017 – 2018 Revised Haiti Humanitarian Plan, funding requirements for cholera programming is the third largest at $21.7 million, behind $76.6 million for food security and $103.8 million for shelter/NFI needs. In 2013, the Government of Haiti launched an oral cholera vaccination (OCV) campaign in two regions: Cerca Carvajal and Petite Anse. These regions were chosen because of particularly high attack rates, sanitation infrastructure, and access to healthcare. This vaccination effort was slightly controversial because the WHO guidelines at the time did not encourage mass vaccination campaigns in areas where outbreaks had already occurred. Prior to the 2010 outbreak in Haiti, vaccination campaigns were thought to detract from more important prevention measures like water treatment and good hygiene. Relative success rates (up to 65% or higher protective effectiveness 5 years after vaccination ) in recent vaccination campaigns in Haiti and other countries affected by cholera has led to more widespread use of oral cholera vaccine programs and a change in the WHO guidelines to encourage use of vaccines in addition to other prevention and treatment strategies. At the end of 2016, former UN Secretary General Ban Ki Moon presented the "New UN System Approach on Cholera in Haiti". This two-track approach marked the UN's acceptance of responsibility for the introduction of cholera in Haiti and demonstrated its commitment to the eradication of the disease in Haiti. Since the 2016 admission of guilt, there has been increased coordination and goodwill between the Government of Haiti and UN, resulting in great strides towards the elimination of cholera. 2017 was a hallmark year in the elimination of cholera from Haiti. The 2017 – 2018 Haiti Revised Humanitarian Plan reports, "As of 31 December 2017, 13,682 suspected cholera cases and 150 deaths had been registered in the country in 2017 compared to 41,955 cases and 451 deaths for the same period in 2016, a decrease of 67% in both cases". Newly developed rapid response teams are largely to credit for the reduction in disease incidence. [ citation needed ] The ability for the humanitarian sector to act quickly and bounce back following Hurricane Matthew in 2016, as well as to maintain the downward trend during the heavy rain season, demonstrates progress in the eradication of cholera in Haiti. [ citation needed ] Track 1 of the New UN System Approach on Cholera in Haiti aims to "intensify efforts to respond to and reduce the incidence of cholera in Haiti" through three main projects. The first is strengthening and supporting the rapid response framework developed by the Haitian Government which deploys to communities where cholera is suspected within 48-hours. There are currently 13 government led rapid response teams, and 60 mobile teams of humanitarian actors that support the rapid response teams. The goal of rapid response teams is to cut the transmission of cholera by first setting up a perimeter called a cordon sanitaire and investigating the source of the outbreak at the household level. This investigation is coupled with education and awareness raising on cholera prevention, administering oral prophylaxis and distribution of WASH kits. If an outbreak is confirmed, temporary chlorination points are installed on community water sources. People treated for cholera by the rapid response teams are then recruited to Community Engagement & Hygiene Awareness (CEHA) teams. The CEHA teams return to their communities to conduct outreach and sensitization on how to cut transmission and assist the government in monitoring water sources. This rapid response design with the assistance of the CEHA teams is responsible for a major decline in disease incidence in the Ouest department in 2017. As long as funding continues to support rapid response, a continued decline in disease incidence can be suspected. [ citation needed ] The second project of track 1 is the continued support of oral cholera vaccination campaigns as a preventative measure. In 2018, the oral cholera vaccine campaign will focus on departments with the highest incidence of disease, particularly Artibonite and Centre departments. The final aim of track 1 is to "more effectively address… the medium/longer term issues of water, sanitation and health systems". The 2010 earthquake and subsequent cholera outbreak/epidemic exposed to the international community how vulnerable the Haitian water, sanitation, and health infrastructure was. Cholera and other water-borne diseases will continue to circulate in Haiti as long as large sections of their population do not have access to improved water and sanitation facilities. As part of the UN's "New Way of Working" which aims to bridge the development and humanitarian gap, the UN will be working with major development actors including the World Bank and the International Development Bank to address infrastructure vulnerabilities that put Haiti at risk of protracted crisis. The "New Way of Working" aims to draw from funding sources on both sides of the spectrum, both development and humanitarian, to work towards the Sustainable Development Goals. No joint funded projects have been reported in Haiti yet. [ citation needed ] The second track of the New UN System Approach on Cholera in Haiti proposes to provide material assistance to individuals and families who were most affected by cholera. The material assistance package is the UN's attempt at reparations after accepting responsibility for the introduction of cholera in Haiti. The UN reports, "nearly 800,000 Haitians have been infected by cholera since 2010 [as of 2016] and more than 9,000 have died". First, consultations will be conducted with the community to identify what materials will be of greatest impact. [ citation needed ] 2020 Update: January of this year marked the 10-year anniversary of the devastating earthquake in Haiti.  In addition, to the lives lost in the earthquake thousands of lives have been affected by the introduction of Cholera to Haiti by UN peacekeepers in Nepal. It is estimated that over the last ten years 820,000 cases and nearly 10,000 deaths have been reported as of January 18, 2020. We briefly describe an update on the cholera epidemic in Haiti since 2016. In 2015, Haiti had more reported cases of cholera per population than any other country and in 2016 Hurricane Matthew added a new urgency to mitigating the suffering in Haiti due to Cholera. In the same year the UN apologized to the Haitian people for the epidemic, after scientific studies linked the cholera epidemic to UN peacekeepers that were not screened for the disease prior to their arrival in Haiti after the earthquake. and pledged to provide 400 million dollars in two years to implement "Track 1" and "Track 2" aimed at providing water sanitation and improved access to treatment and material assistance to Haitians affected by the cholera epidemic respectively. However, to date only 21 million dollars have been raised and 3 million dollars have been utilized. While to date only 5% of the funds for these tracks have been raised ongoing humanitarian efforts by the UN, other NGO's, and the Haitian government the new cases of Cholera have drastically decreased in the last 5 years.  A series of studies from 2013 to 2016 proved that the combination of chlorination and cholera vaccination could eliminate cholera in one of the poorest areas in Haiti. After Hurricane Matthew in 2016, the WHO and other technical partners developed teams to investigate the scale of cholera outbreaks. Then in October 2016, the Haitian Ministry of Public Health and Population requested and received 1 million doses of the oral cholera vaccine, partially funded by Gavi, the vaccine alliance. The WHO and other partners including UNICEF, International Medical Corps, the Red Cross and Gavi, the vaccine alliance teams reached over 729,000 people most affected by Hurricane Matthew. These and ongoing efforts by the Haitian government and humanitarian aid have only continued to decrease the number of cholera cases in Haiti. In 2018 only 3700 cholera cases and 41 deaths were reported from 90% of the departments in Haiti. Then in 2019 the UN announced that Haiti had been cholera free for one year, with the last confirmed case reported to be in the Artibonite in January 2019. However,  in order to obtain validation that cholera has ended in Haiti the country must maintain effective surveillance systems and remain cholera free for two more years. The first challenge to the eradication of cholera in Haiti is the country's vulnerability to disasters, putting it in a state of protracted crises. The climax of cholera incidence in Haiti was in 2011 with 352,000 new cases following the introduction of cholera in Haiti in late 2010. Incidence rates gradually declined until 2016 when there was another spike in the transmission and incidence of cholera following Hurricane Matthew's destruction in Haiti from 2–5 October 2016. There was a rise in cholera incidence from 32,000 new cases in 2015 to 42,000 new cases in 2016. By re-damaging Haiti's fragile water and sanitation infrastructure, Hurricane Matthew allowed cholera to rear its head. These figures demonstrate that the fight against cholera in Haiti, while improving, is on unstable ground. This indicates that while eradication efforts have largely been focused on vaccination and community education to prevent transmission, and oral rehydration to reduce mortality, the underlying vulnerabilities that perpetuate the disaster remain, particularly insufficient and unequal access to improved water and sanitation. While the Government of Haiti's Cholera Elimination Plan (PNEC) 2013 – 2022 and the New UN System Approach on Cholera in Haiti (see solutions below for more information) lay out plans for the elimination of cholera in Haiti by 2022, these are entirely dependent on funding. In former Secretary General Moon's 5 December 2016 remarks he says, "Without political will and financial support from the membership of the United Nations, we have only good intentions and words. Words are powerful – but they cannot replace action and material support". Due to the infectious nature of cholera, any lapse in funding for programming will likely result in setbacks in elimination. As of 2017, funding for cholera is at risk due to increasing food insecurity and shelter needs for Haitian refugees returning from the Dominican Republic. In the 2017 – 2018 Revised Haiti Humanitarian Plan, funding requirements for cholera programming is the third largest at $21.7 million, behind $76.6 million for food security and $103.8 million for shelter/NFI needs. The first challenge to the eradication of cholera in Haiti is the country's vulnerability to disasters, putting it in a state of protracted crises. The climax of cholera incidence in Haiti was in 2011 with 352,000 new cases following the introduction of cholera in Haiti in late 2010. Incidence rates gradually declined until 2016 when there was another spike in the transmission and incidence of cholera following Hurricane Matthew's destruction in Haiti from 2–5 October 2016. There was a rise in cholera incidence from 32,000 new cases in 2015 to 42,000 new cases in 2016. By re-damaging Haiti's fragile water and sanitation infrastructure, Hurricane Matthew allowed cholera to rear its head. These figures demonstrate that the fight against cholera in Haiti, while improving, is on unstable ground. This indicates that while eradication efforts have largely been focused on vaccination and community education to prevent transmission, and oral rehydration to reduce mortality, the underlying vulnerabilities that perpetuate the disaster remain, particularly insufficient and unequal access to improved water and sanitation. While the Government of Haiti's Cholera Elimination Plan (PNEC) 2013 – 2022 and the New UN System Approach on Cholera in Haiti (see solutions below for more information) lay out plans for the elimination of cholera in Haiti by 2022, these are entirely dependent on funding. In former Secretary General Moon's 5 December 2016 remarks he says, "Without political will and financial support from the membership of the United Nations, we have only good intentions and words. Words are powerful – but they cannot replace action and material support". Due to the infectious nature of cholera, any lapse in funding for programming will likely result in setbacks in elimination. As of 2017, funding for cholera is at risk due to increasing food insecurity and shelter needs for Haitian refugees returning from the Dominican Republic. In the 2017 – 2018 Revised Haiti Humanitarian Plan, funding requirements for cholera programming is the third largest at $21.7 million, behind $76.6 million for food security and $103.8 million for shelter/NFI needs. In 2013, the Government of Haiti launched an oral cholera vaccination (OCV) campaign in two regions: Cerca Carvajal and Petite Anse. These regions were chosen because of particularly high attack rates, sanitation infrastructure, and access to healthcare. This vaccination effort was slightly controversial because the WHO guidelines at the time did not encourage mass vaccination campaigns in areas where outbreaks had already occurred. Prior to the 2010 outbreak in Haiti, vaccination campaigns were thought to detract from more important prevention measures like water treatment and good hygiene. Relative success rates (up to 65% or higher protective effectiveness 5 years after vaccination ) in recent vaccination campaigns in Haiti and other countries affected by cholera has led to more widespread use of oral cholera vaccine programs and a change in the WHO guidelines to encourage use of vaccines in addition to other prevention and treatment strategies. At the end of 2016, former UN Secretary General Ban Ki Moon presented the "New UN System Approach on Cholera in Haiti". This two-track approach marked the UN's acceptance of responsibility for the introduction of cholera in Haiti and demonstrated its commitment to the eradication of the disease in Haiti. Since the 2016 admission of guilt, there has been increased coordination and goodwill between the Government of Haiti and UN, resulting in great strides towards the elimination of cholera. 2017 was a hallmark year in the elimination of cholera from Haiti. The 2017 – 2018 Haiti Revised Humanitarian Plan reports, "As of 31 December 2017, 13,682 suspected cholera cases and 150 deaths had been registered in the country in 2017 compared to 41,955 cases and 451 deaths for the same period in 2016, a decrease of 67% in both cases". Newly developed rapid response teams are largely to credit for the reduction in disease incidence. [ citation needed ] The ability for the humanitarian sector to act quickly and bounce back following Hurricane Matthew in 2016, as well as to maintain the downward trend during the heavy rain season, demonstrates progress in the eradication of cholera in Haiti. [ citation needed ] Track 1 of the New UN System Approach on Cholera in Haiti aims to "intensify efforts to respond to and reduce the incidence of cholera in Haiti" through three main projects. The first is strengthening and supporting the rapid response framework developed by the Haitian Government which deploys to communities where cholera is suspected within 48-hours. There are currently 13 government led rapid response teams, and 60 mobile teams of humanitarian actors that support the rapid response teams. The goal of rapid response teams is to cut the transmission of cholera by first setting up a perimeter called a cordon sanitaire and investigating the source of the outbreak at the household level. This investigation is coupled with education and awareness raising on cholera prevention, administering oral prophylaxis and distribution of WASH kits. If an outbreak is confirmed, temporary chlorination points are installed on community water sources. People treated for cholera by the rapid response teams are then recruited to Community Engagement & Hygiene Awareness (CEHA) teams. The CEHA teams return to their communities to conduct outreach and sensitization on how to cut transmission and assist the government in monitoring water sources. This rapid response design with the assistance of the CEHA teams is responsible for a major decline in disease incidence in the Ouest department in 2017. As long as funding continues to support rapid response, a continued decline in disease incidence can be suspected. [ citation needed ] The second project of track 1 is the continued support of oral cholera vaccination campaigns as a preventative measure. In 2018, the oral cholera vaccine campaign will focus on departments with the highest incidence of disease, particularly Artibonite and Centre departments. The final aim of track 1 is to "more effectively address… the medium/longer term issues of water, sanitation and health systems". The 2010 earthquake and subsequent cholera outbreak/epidemic exposed to the international community how vulnerable the Haitian water, sanitation, and health infrastructure was. Cholera and other water-borne diseases will continue to circulate in Haiti as long as large sections of their population do not have access to improved water and sanitation facilities. As part of the UN's "New Way of Working" which aims to bridge the development and humanitarian gap, the UN will be working with major development actors including the World Bank and the International Development Bank to address infrastructure vulnerabilities that put Haiti at risk of protracted crisis. The "New Way of Working" aims to draw from funding sources on both sides of the spectrum, both development and humanitarian, to work towards the Sustainable Development Goals. No joint funded projects have been reported in Haiti yet. [ citation needed ] The second track of the New UN System Approach on Cholera in Haiti proposes to provide material assistance to individuals and families who were most affected by cholera. The material assistance package is the UN's attempt at reparations after accepting responsibility for the introduction of cholera in Haiti. The UN reports, "nearly 800,000 Haitians have been infected by cholera since 2010 [as of 2016] and more than 9,000 have died". First, consultations will be conducted with the community to identify what materials will be of greatest impact. [ citation needed ] 2020 Update: January of this year marked the 10-year anniversary of the devastating earthquake in Haiti.  In addition, to the lives lost in the earthquake thousands of lives have been affected by the introduction of Cholera to Haiti by UN peacekeepers in Nepal. It is estimated that over the last ten years 820,000 cases and nearly 10,000 deaths have been reported as of January 18, 2020. We briefly describe an update on the cholera epidemic in Haiti since 2016. In 2015, Haiti had more reported cases of cholera per population than any other country and in 2016 Hurricane Matthew added a new urgency to mitigating the suffering in Haiti due to Cholera. In the same year the UN apologized to the Haitian people for the epidemic, after scientific studies linked the cholera epidemic to UN peacekeepers that were not screened for the disease prior to their arrival in Haiti after the earthquake. and pledged to provide 400 million dollars in two years to implement "Track 1" and "Track 2" aimed at providing water sanitation and improved access to treatment and material assistance to Haitians affected by the cholera epidemic respectively. However, to date only 21 million dollars have been raised and 3 million dollars have been utilized. While to date only 5% of the funds for these tracks have been raised ongoing humanitarian efforts by the UN, other NGO's, and the Haitian government the new cases of Cholera have drastically decreased in the last 5 years.  A series of studies from 2013 to 2016 proved that the combination of chlorination and cholera vaccination could eliminate cholera in one of the poorest areas in Haiti. After Hurricane Matthew in 2016, the WHO and other technical partners developed teams to investigate the scale of cholera outbreaks. Then in October 2016, the Haitian Ministry of Public Health and Population requested and received 1 million doses of the oral cholera vaccine, partially funded by Gavi, the vaccine alliance. The WHO and other partners including UNICEF, International Medical Corps, the Red Cross and Gavi, the vaccine alliance teams reached over 729,000 people most affected by Hurricane Matthew. These and ongoing efforts by the Haitian government and humanitarian aid have only continued to decrease the number of cholera cases in Haiti. In 2018 only 3700 cholera cases and 41 deaths were reported from 90% of the departments in Haiti. Then in 2019 the UN announced that Haiti had been cholera free for one year, with the last confirmed case reported to be in the Artibonite in January 2019. However,  in order to obtain validation that cholera has ended in Haiti the country must maintain effective surveillance systems and remain cholera free for two more years. In 2013, the Government of Haiti launched an oral cholera vaccination (OCV) campaign in two regions: Cerca Carvajal and Petite Anse. These regions were chosen because of particularly high attack rates, sanitation infrastructure, and access to healthcare. This vaccination effort was slightly controversial because the WHO guidelines at the time did not encourage mass vaccination campaigns in areas where outbreaks had already occurred. Prior to the 2010 outbreak in Haiti, vaccination campaigns were thought to detract from more important prevention measures like water treatment and good hygiene. Relative success rates (up to 65% or higher protective effectiveness 5 years after vaccination ) in recent vaccination campaigns in Haiti and other countries affected by cholera has led to more widespread use of oral cholera vaccine programs and a change in the WHO guidelines to encourage use of vaccines in addition to other prevention and treatment strategies. At the end of 2016, former UN Secretary General Ban Ki Moon presented the "New UN System Approach on Cholera in Haiti". This two-track approach marked the UN's acceptance of responsibility for the introduction of cholera in Haiti and demonstrated its commitment to the eradication of the disease in Haiti. Since the 2016 admission of guilt, there has been increased coordination and goodwill between the Government of Haiti and UN, resulting in great strides towards the elimination of cholera. 2017 was a hallmark year in the elimination of cholera from Haiti. The 2017 – 2018 Haiti Revised Humanitarian Plan reports, "As of 31 December 2017, 13,682 suspected cholera cases and 150 deaths had been registered in the country in 2017 compared to 41,955 cases and 451 deaths for the same period in 2016, a decrease of 67% in both cases". Newly developed rapid response teams are largely to credit for the reduction in disease incidence. [ citation needed ] The ability for the humanitarian sector to act quickly and bounce back following Hurricane Matthew in 2016, as well as to maintain the downward trend during the heavy rain season, demonstrates progress in the eradication of cholera in Haiti. [ citation needed ] Track 1 of the New UN System Approach on Cholera in Haiti aims to "intensify efforts to respond to and reduce the incidence of cholera in Haiti" through three main projects. The first is strengthening and supporting the rapid response framework developed by the Haitian Government which deploys to communities where cholera is suspected within 48-hours. There are currently 13 government led rapid response teams, and 60 mobile teams of humanitarian actors that support the rapid response teams. The goal of rapid response teams is to cut the transmission of cholera by first setting up a perimeter called a cordon sanitaire and investigating the source of the outbreak at the household level. This investigation is coupled with education and awareness raising on cholera prevention, administering oral prophylaxis and distribution of WASH kits. If an outbreak is confirmed, temporary chlorination points are installed on community water sources. People treated for cholera by the rapid response teams are then recruited to Community Engagement & Hygiene Awareness (CEHA) teams. The CEHA teams return to their communities to conduct outreach and sensitization on how to cut transmission and assist the government in monitoring water sources. This rapid response design with the assistance of the CEHA teams is responsible for a major decline in disease incidence in the Ouest department in 2017. As long as funding continues to support rapid response, a continued decline in disease incidence can be suspected. [ citation needed ] The second project of track 1 is the continued support of oral cholera vaccination campaigns as a preventative measure. In 2018, the oral cholera vaccine campaign will focus on departments with the highest incidence of disease, particularly Artibonite and Centre departments. The final aim of track 1 is to "more effectively address… the medium/longer term issues of water, sanitation and health systems". The 2010 earthquake and subsequent cholera outbreak/epidemic exposed to the international community how vulnerable the Haitian water, sanitation, and health infrastructure was. Cholera and other water-borne diseases will continue to circulate in Haiti as long as large sections of their population do not have access to improved water and sanitation facilities. As part of the UN's "New Way of Working" which aims to bridge the development and humanitarian gap, the UN will be working with major development actors including the World Bank and the International Development Bank to address infrastructure vulnerabilities that put Haiti at risk of protracted crisis. The "New Way of Working" aims to draw from funding sources on both sides of the spectrum, both development and humanitarian, to work towards the Sustainable Development Goals. No joint funded projects have been reported in Haiti yet. [ citation needed ] The second track of the New UN System Approach on Cholera in Haiti proposes to provide material assistance to individuals and families who were most affected by cholera. The material assistance package is the UN's attempt at reparations after accepting responsibility for the introduction of cholera in Haiti. The UN reports, "nearly 800,000 Haitians have been infected by cholera since 2010 [as of 2016] and more than 9,000 have died". First, consultations will be conducted with the community to identify what materials will be of greatest impact. [ citation needed ] 2020 Update: January of this year marked the 10-year anniversary of the devastating earthquake in Haiti.  In addition, to the lives lost in the earthquake thousands of lives have been affected by the introduction of Cholera to Haiti by UN peacekeepers in Nepal. It is estimated that over the last ten years 820,000 cases and nearly 10,000 deaths have been reported as of January 18, 2020. We briefly describe an update on the cholera epidemic in Haiti since 2016. In 2015, Haiti had more reported cases of cholera per population than any other country and in 2016 Hurricane Matthew added a new urgency to mitigating the suffering in Haiti due to Cholera. In the same year the UN apologized to the Haitian people for the epidemic, after scientific studies linked the cholera epidemic to UN peacekeepers that were not screened for the disease prior to their arrival in Haiti after the earthquake. and pledged to provide 400 million dollars in two years to implement "Track 1" and "Track 2" aimed at providing water sanitation and improved access to treatment and material assistance to Haitians affected by the cholera epidemic respectively. However, to date only 21 million dollars have been raised and 3 million dollars have been utilized. While to date only 5% of the funds for these tracks have been raised ongoing humanitarian efforts by the UN, other NGO's, and the Haitian government the new cases of Cholera have drastically decreased in the last 5 years.  A series of studies from 2013 to 2016 proved that the combination of chlorination and cholera vaccination could eliminate cholera in one of the poorest areas in Haiti. After Hurricane Matthew in 2016, the WHO and other technical partners developed teams to investigate the scale of cholera outbreaks. Then in October 2016, the Haitian Ministry of Public Health and Population requested and received 1 million doses of the oral cholera vaccine, partially funded by Gavi, the vaccine alliance. The WHO and other partners including UNICEF, International Medical Corps, the Red Cross and Gavi, the vaccine alliance teams reached over 729,000 people most affected by Hurricane Matthew. These and ongoing efforts by the Haitian government and humanitarian aid have only continued to decrease the number of cholera cases in Haiti. In 2018 only 3700 cholera cases and 41 deaths were reported from 90% of the departments in Haiti. Then in 2019 the UN announced that Haiti had been cholera free for one year, with the last confirmed case reported to be in the Artibonite in January 2019. However,  in order to obtain validation that cholera has ended in Haiti the country must maintain effective surveillance systems and remain cholera free for two more years. Track 1 of the New UN System Approach on Cholera in Haiti aims to "intensify efforts to respond to and reduce the incidence of cholera in Haiti" through three main projects. The first is strengthening and supporting the rapid response framework developed by the Haitian Government which deploys to communities where cholera is suspected within 48-hours. There are currently 13 government led rapid response teams, and 60 mobile teams of humanitarian actors that support the rapid response teams. The goal of rapid response teams is to cut the transmission of cholera by first setting up a perimeter called a cordon sanitaire and investigating the source of the outbreak at the household level. This investigation is coupled with education and awareness raising on cholera prevention, administering oral prophylaxis and distribution of WASH kits. If an outbreak is confirmed, temporary chlorination points are installed on community water sources. People treated for cholera by the rapid response teams are then recruited to Community Engagement & Hygiene Awareness (CEHA) teams. The CEHA teams return to their communities to conduct outreach and sensitization on how to cut transmission and assist the government in monitoring water sources. This rapid response design with the assistance of the CEHA teams is responsible for a major decline in disease incidence in the Ouest department in 2017. As long as funding continues to support rapid response, a continued decline in disease incidence can be suspected. [ citation needed ] The second project of track 1 is the continued support of oral cholera vaccination campaigns as a preventative measure. In 2018, the oral cholera vaccine campaign will focus on departments with the highest incidence of disease, particularly Artibonite and Centre departments. The final aim of track 1 is to "more effectively address… the medium/longer term issues of water, sanitation and health systems". The 2010 earthquake and subsequent cholera outbreak/epidemic exposed to the international community how vulnerable the Haitian water, sanitation, and health infrastructure was. Cholera and other water-borne diseases will continue to circulate in Haiti as long as large sections of their population do not have access to improved water and sanitation facilities. As part of the UN's "New Way of Working" which aims to bridge the development and humanitarian gap, the UN will be working with major development actors including the World Bank and the International Development Bank to address infrastructure vulnerabilities that put Haiti at risk of protracted crisis. The "New Way of Working" aims to draw from funding sources on both sides of the spectrum, both development and humanitarian, to work towards the Sustainable Development Goals. No joint funded projects have been reported in Haiti yet. [ citation needed ]The second track of the New UN System Approach on Cholera in Haiti proposes to provide material assistance to individuals and families who were most affected by cholera. The material assistance package is the UN's attempt at reparations after accepting responsibility for the introduction of cholera in Haiti. The UN reports, "nearly 800,000 Haitians have been infected by cholera since 2010 [as of 2016] and more than 9,000 have died". First, consultations will be conducted with the community to identify what materials will be of greatest impact. [ citation needed ] 2020 Update: January of this year marked the 10-year anniversary of the devastating earthquake in Haiti.  In addition, to the lives lost in the earthquake thousands of lives have been affected by the introduction of Cholera to Haiti by UN peacekeepers in Nepal. It is estimated that over the last ten years 820,000 cases and nearly 10,000 deaths have been reported as of January 18, 2020. We briefly describe an update on the cholera epidemic in Haiti since 2016. In 2015, Haiti had more reported cases of cholera per population than any other country and in 2016 Hurricane Matthew added a new urgency to mitigating the suffering in Haiti due to Cholera. In the same year the UN apologized to the Haitian people for the epidemic, after scientific studies linked the cholera epidemic to UN peacekeepers that were not screened for the disease prior to their arrival in Haiti after the earthquake. and pledged to provide 400 million dollars in two years to implement "Track 1" and "Track 2" aimed at providing water sanitation and improved access to treatment and material assistance to Haitians affected by the cholera epidemic respectively. However, to date only 21 million dollars have been raised and 3 million dollars have been utilized. While to date only 5% of the funds for these tracks have been raised ongoing humanitarian efforts by the UN, other NGO's, and the Haitian government the new cases of Cholera have drastically decreased in the last 5 years.  A series of studies from 2013 to 2016 proved that the combination of chlorination and cholera vaccination could eliminate cholera in one of the poorest areas in Haiti. After Hurricane Matthew in 2016, the WHO and other technical partners developed teams to investigate the scale of cholera outbreaks. Then in October 2016, the Haitian Ministry of Public Health and Population requested and received 1 million doses of the oral cholera vaccine, partially funded by Gavi, the vaccine alliance. The WHO and other partners including UNICEF, International Medical Corps, the Red Cross and Gavi, the vaccine alliance teams reached over 729,000 people most affected by Hurricane Matthew. These and ongoing efforts by the Haitian government and humanitarian aid have only continued to decrease the number of cholera cases in Haiti. In 2018 only 3700 cholera cases and 41 deaths were reported from 90% of the departments in Haiti. Then in 2019 the UN announced that Haiti had been cholera free for one year, with the last confirmed case reported to be in the Artibonite in January 2019. However,  in order to obtain validation that cholera has ended in Haiti the country must maintain effective surveillance systems and remain cholera free for two more years.

Wiki

Cholera

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

Cholera vaccine

AU : B2 none A cholera vaccine is a vaccine that is effective at preventing cholera . The currently recommended cholera vaccines are administered orally to elicit a protective local mucosal immune response in the gut, which was poorly achieved with the injectable vaccines that were used until the 1970s. The first effective oral cholera vaccine was Dukoral, developed in Sweden in the 1980s. For the first six months after vaccination it provides about 85 percent protection, which decreases to approximately 60 percent during the first two years. When enough of the population is immunized, it may protect those who have not been immunized thereby increasing the total protective impact to more than 90 percent (known as herd immunity ). The World Health Organization (WHO) currently recommends the use of three oral cholera vaccines – Dukoral, Shanchol and Euvichol-Plus – in combination with other measures among those at high risk for cholera. Two vaccine doses with a 1-6 week interval are typically recommended. The duration of protection is at least two years in adults and six months in children aged 1–5 years. A live, attenuated single dose oral vaccine is available for those traveling to an area where cholera is common but is not WHO approved for public health use. The available types of oral vaccine are generally safe. Mild abdominal pain or diarrhea may occur. They are safe in pregnancy and in those with poor immune function . They are licensed for use in more than 60 countries. In countries where the disease is common, the vaccine appears to be cost effective. The first cholera vaccines were developed in the late 19th century. They were the first widely used vaccine that was made in a laboratory but were largely abandoned in the 1970s due to their then documented reactogenicity and poor efficacy . Oral cholera vaccines were first introduced in the 1990s. It is on the World Health Organization's List of Essential Medicines . In the late twentieth century, oral cholera vaccines started to be used on a massive scale, with millions of vaccinations taking place, as a tool to control cholera outbreaks in addition to the traditional interventions of improving safe water supplies, sanitation, handwashing, and other means of improving hygiene. The Dukoral vaccine, which combines formalin - and heat-killed whole cells of Vibrio cholerae O1 and a recombinant cholera toxin B subunit, was licensed in 1991 and has been used widely, mainly for travellers. The Shanchol bivalent vaccine, which combines the O1 and O139 serogroups , was originally developed in Vietnam under the name mORCVAX in 1997 and given in 20 million doses in Vietnam´s public health programme during the following decade through targeted mass vaccination of school-aged children in cholera endemic regions. The World Health Organization (WHO) recommends both preventive and reactive use of the vaccine, making the following key statements: WHO recommends that current available cholera vaccines be used as complements to traditional control and preventive measures in areas where the disease is endemic and should be considered in areas at risk for outbreaks. Vaccination should not disrupt the provision of other high priority health interventions to control or prevent cholera outbreaks.... Reactive vaccination might be considered in view of limiting the extent of large prolonged outbreaks, provided the local infrastructure allows it, and an in-depth analysis of past cholera data and identification of a defined target area have been performed. Although the vaccine specific protection observed, 60–70 percent, has been described as "moderate", herd immunity can multiply the effectiveness of vaccination. Dukoral has been licensed for children two years of age and older, Shanchol and Euvichol-Plus for children one year of age and older. The administration of the vaccine to adults confers additional indirect protection (herd immunity) also to children. The WHO as of 2013 established a revolving stockpile, initially of only two million oral cholera vaccine doses. With donations from mainly the GAVI Alliance the stockpile has progressively expanded to now more than 40 million doses per year. It consists mainly of the Euvichol-Plus oral cholera vaccine being produced in South Korea. In total more than 150 million doses from the stockpile have been given in mass campaigns against both epidemic and endemic cholera in more than 25 cholera afflicted countries. A set goal of WHO´s Global Task Force for Cholera Control (GTFCC) is, by using oral cholera vaccine and other available tools, by 2030 to have reduced cholera deaths by more than 90% and stopped transmission globally. The oral vaccines are generally of two forms: inactivated and attenuated . [ citation needed ] The first developed effective oral cholera vaccine, Dukoral, is a monovalent inactivated vaccine containing killed whole cells of V. cholerae O1 plus additional recombinant cholera toxin B subunit. Bacterial strains of both Inaba and Ogawa serotypes and of El Tor and Classical biotypes are included in the vaccine. Dukoral is taken orally with bicarbonate buffer, which protects the antigens from the gastric acid. The vaccine acts by inducing antibodies against both the bacterial components and CTB . The antibacterial intestinal antibodies prevent the bacteria from attaching to the intestinal wall, thereby impeding colonisation of V. cholerae O1. The anti-toxin intestinal antibodies prevent the cholera toxin from binding to the intestinal mucosal surface, thereby preventing the toxin-mediated diarrhoeal symptoms. The two later inactivated oral cholera vaccines recommended by WHO, Shanchol and Euvichol-Plus, have an identical composition, containing killed whole cells of V. cholerae O1 (the same components as in Dukoral) plus formalin-killed V. cholerae O139 bacteria. [ citation needed ] A live, attenuated oral vaccine (CVD 103-HgR or Vaxchora), derived from a serogroup O1 classical Inaba strain, was approved for use in travellers by the US FDA in 2016. In 2024, the Euvichol-S vaccine, an optimized version of Euvichol-Plus, received WHO prequalification. This streamlined formulation is designed to maintain effectiveness while reducing production costs, significantly boosting the global oral cholera vaccine supply to 50 million doses, up from 38 million. This increase addresses the growing demand amid rising cholera outbreaks since 2021. Although rarely in use, the injected cholera vaccines can be effective for people living where cholera is common. While being ineffective in young children, in such areas they can offer some degree of protection in adults and older children for up to six months. The oral vaccines are generally of two forms: inactivated and attenuated . [ citation needed ] The first developed effective oral cholera vaccine, Dukoral, is a monovalent inactivated vaccine containing killed whole cells of V. cholerae O1 plus additional recombinant cholera toxin B subunit. Bacterial strains of both Inaba and Ogawa serotypes and of El Tor and Classical biotypes are included in the vaccine. Dukoral is taken orally with bicarbonate buffer, which protects the antigens from the gastric acid. The vaccine acts by inducing antibodies against both the bacterial components and CTB . The antibacterial intestinal antibodies prevent the bacteria from attaching to the intestinal wall, thereby impeding colonisation of V. cholerae O1. The anti-toxin intestinal antibodies prevent the cholera toxin from binding to the intestinal mucosal surface, thereby preventing the toxin-mediated diarrhoeal symptoms. The two later inactivated oral cholera vaccines recommended by WHO, Shanchol and Euvichol-Plus, have an identical composition, containing killed whole cells of V. cholerae O1 (the same components as in Dukoral) plus formalin-killed V. cholerae O139 bacteria. [ citation needed ] A live, attenuated oral vaccine (CVD 103-HgR or Vaxchora), derived from a serogroup O1 classical Inaba strain, was approved for use in travellers by the US FDA in 2016. In 2024, the Euvichol-S vaccine, an optimized version of Euvichol-Plus, received WHO prequalification. This streamlined formulation is designed to maintain effectiveness while reducing production costs, significantly boosting the global oral cholera vaccine supply to 50 million doses, up from 38 million. This increase addresses the growing demand amid rising cholera outbreaks since 2021. Although rarely in use, the injected cholera vaccines can be effective for people living where cholera is common. While being ineffective in young children, in such areas they can offer some degree of protection in adults and older children for up to six months. Both of the available types of oral vaccine are generally safe. Mild abdominal pain or diarrhea may occur. They are safe in pregnancy and in those with poor immune function . They are licensed for use in more than 60 countries. In countries where the disease is common, the vaccine appears to be cost effective. The first cholera vaccines were developed in the late 19th century. There were several pioneers in the development of the vaccine: Oral cholera vaccines were first introduced in the 1990s. In 2016, the U.S. Food and Drug Administration (FDA) approved Vaxchora, a single-dose oral vaccine to prevent cholera for travelers. As of June 2016 [ update ] , Vaxchora was the only FDA-approved vaccine for the prevention of cholera. The cost to immunize against cholera is between US$0.10 and US$4.00 per vaccination. The Vaxchora vaccine can cost more than US$250 . In 2016, the U.S. Food and Drug Administration (FDA) approved Vaxchora, a single-dose oral vaccine to prevent cholera for travelers. As of June 2016 [ update ] , Vaxchora was the only FDA-approved vaccine for the prevention of cholera. The cost to immunize against cholera is between US$0.10 and US$4.00 per vaccination. The Vaxchora vaccine can cost more than US$250 .

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1826–1837_cholera_pandemic/html

1826–1837 cholera pandemic

The second cholera pandemic (1826–1837), also known as the Asiatic cholera pandemic , was a cholera pandemic that reached from India across Western Asia to Europe , Great Britain , and the Americas , as well as east to China and Japan . Cholera caused more deaths, more quickly, than any other epidemic disease in the 19th century. [ citation needed ] The medical community now believes cholera to be exclusively a human disease, spread through many means of travel during the time, and transmitted through warm fecal-contaminated river waters and contaminated foods. During the second pandemic, the scientific community varied in its beliefs about the causes of cholera.The first cholera pandemic (1817–24) began near Kolkata and spread throughout Southeast Asia to the Middle East, eastern Africa, and the Mediterranean coast. While cholera had spread across India many times previously, this outbreak went farther; it reached as far as China and the Mediterranean Sea before receding. Hundreds of thousands of people died as a result of this pandemic , including many British soldiers , which attracted European attention. This was the first of several cholera pandemics to sweep through Asia and Europe during the 19th and 20th centuries. This first pandemic spread over an unprecedented range of territory, affecting many countries throughout Asia. Historians believe that the first pandemic had lingered in Indonesia and the Philippines in 1830. [ citation needed ] Although not much is known about the journey of the cholera pandemic in east India, many believe that this pandemic began, like the first, with outbreaks along the Ganges Delta in India. From there, the disease spread along trade routes to cover most of India. By 1828, the disease had traveled to China. Cholera was also reported in China in 1826 and 1835, and in Japan in 1831. In 1829, Iran was apparently infected with cholera from Afghanistan. [ citation needed ] Cholera reached the southern tips of the Ural Mountains in 1829. On 26 August 1829, the first cholera case was recorded in Orenburg with reports of outbreaks in Bugulma (7 November), Buguruslan (5 December), Menzelinsk (2 January 1830), and Belebey (6 January). With 3,500 cases including 865 fatal ones in Orenburg province, the epidemic stopped by February 1830. The second cholera pandemic spread from Russia to the rest of Europe, claiming hundreds of thousands of lives. By 1831, the epidemic had infiltrated Russia's main cities and towns. Russian soldiers brought the disease to Poland in February 1831. There were reported to have been 250,000 cases of cholera and 100,000 deaths in Russia. [ citation needed ] In 1831, it is estimated that up to 100,000 deaths occurred in Hungary . The cholera epidemic struck Warsaw during the November Uprising between 16 May and 20 August 1831; 4,734 people fell ill and 2,524 died. The epidemic of cholera brought to Poland and East Prussia by Russian soldiers forced Prussian authorities to close their borders to Russian transports. There were Cholera Riots in the Russian Empire caused by the government's anticholera measures. [ citation needed ] By early 1831, frequent reports of the spread of the pandemic in Russia prompted the British government to issue quarantine orders for ships sailing from Russia to British ports. By late summer, with the disease appearing more likely to spread to Britain, its board of health, in accordance with the prevailing miasma theory , issued orders recommending as a preventive the burning of "decayed articles, such as rags, cordage, papers, old clothes, hangings...filth of every description removed, clothing and furniture should be submitted to copious effusions of water, and boiled in a strong ley (lye); drains and privies thoroughly cleansed by streams of water and chloride of lime...free and continued admission of fresh air to all parts of the house and furniture should be enjoined for at least a week". Based on the reports of two English doctors who had observed the epidemic in Saint Petersburg , the board of health published a detailed description of the disease's symptoms and onset: Giddiness, sick stomach, nervous agitation, intermittent, slow, or small pulse, cramps beginning at the tops of the fingers and toes, and rapidly approaching the trunk, give the first warning. Vomiting or purging, or both these evacuations of a liquid like rice-water or whey, or barley-water, come on; the features become sharp and contracted, the eye sinks, the look is expressive of terror and wildness; the lips, face, neck, hands, and feet, and soon after the thighs, arms, and whole surface assume a leaden, blue, purple, black, or deep brown tint according to the complexion of the individual, varying in shade with the intensity of the attack. The fingers and toes are reduced in size, the skin and soft parts covering them are wrinkled, shrivelled and folded. The nails put on a bluish pearly white; the larger superficial veins are marked by flat lines of a deeper black; the pulse becomes either small as a thread, and scarcely vibrating, or else totally extinct. The skin is deadly cold and often damp, the tongue always moist, often white and loaded, but flabby and chilled like a piece of dead flesh. The voice is nearly gone; the respiration quick, irregular, and imperfectly performed. The patient speaks in a whisper. He struggles for breath, and often lays his hand on his heart to point out the seat of his distress. Sometimes there are rigid spasms of the legs, thighs, and loins. The secretion of urine is totally suspended; vomiting and purgings, which are far from being the most important or dangerous symptoms, and which in a very great number of cases of the disease, have not been profuse, or have been arrested by medicine early in the attack, succeed. It is evident that the most urgent and peculiar symptom of this disease is the sudden depression of the vital powers: proved by the diminished action of the heart, the coldness of the surface and extremities, and the stagnant state of the whole circulation. From September 1831 to January 1832, a catastrophic cholera epidemic ravaged the lower Euphrates and Tigris regions of what is now Iraq and Iran . In Shushtar , Iran, about half of the city's inhabitants died from cholera. The Mandaean community was hit particularly hard, and all of their priests died in the plague. Yahya Bihram told Julius Heinrich Petermann that there were only 1,500 Mandaean survivors after the plague. The epidemic reached Great Britain in October 1831, appearing in Sunderland , where it was carried by passengers on a ship from the Baltic. It also appeared in Gateshead and Newcastle . In London, the disease claimed 6,536 victims; in Paris, 20,000 died (out of a population of 650,000), with about 100,000 deaths in all of France. In 1832, the epidemic reached Quebec , Ontario , and Nova Scotia in Canada and Detroit and New York City in the United States. [lower-alpha 1] It reached the Pacific coast of North America between 1832 and 1834. The pandemic prompted the passage of the landmark Public Health Act 1848 ( 11 & 12 Vict. c. 63) and the Nuisances Removal and Diseases Prevention Acts, 1848 and 1849, in England. [ citation needed ] In mid-1832, 57 Irish immigrants died who had been laying a stretch of railroad called Duffy's Cut , 30 miles west of Philadelphia. They had all contracted cholera. The first cholera pandemic (1817–24) began near Kolkata and spread throughout Southeast Asia to the Middle East, eastern Africa, and the Mediterranean coast. While cholera had spread across India many times previously, this outbreak went farther; it reached as far as China and the Mediterranean Sea before receding. Hundreds of thousands of people died as a result of this pandemic , including many British soldiers , which attracted European attention. This was the first of several cholera pandemics to sweep through Asia and Europe during the 19th and 20th centuries. This first pandemic spread over an unprecedented range of territory, affecting many countries throughout Asia. Historians believe that the first pandemic had lingered in Indonesia and the Philippines in 1830. [ citation needed ] Although not much is known about the journey of the cholera pandemic in east India, many believe that this pandemic began, like the first, with outbreaks along the Ganges Delta in India. From there, the disease spread along trade routes to cover most of India. By 1828, the disease had traveled to China. Cholera was also reported in China in 1826 and 1835, and in Japan in 1831. In 1829, Iran was apparently infected with cholera from Afghanistan. [ citation needed ] Cholera reached the southern tips of the Ural Mountains in 1829. On 26 August 1829, the first cholera case was recorded in Orenburg with reports of outbreaks in Bugulma (7 November), Buguruslan (5 December), Menzelinsk (2 January 1830), and Belebey (6 January). With 3,500 cases including 865 fatal ones in Orenburg province, the epidemic stopped by February 1830. The second cholera pandemic spread from Russia to the rest of Europe, claiming hundreds of thousands of lives. By 1831, the epidemic had infiltrated Russia's main cities and towns. Russian soldiers brought the disease to Poland in February 1831. There were reported to have been 250,000 cases of cholera and 100,000 deaths in Russia. [ citation needed ] In 1831, it is estimated that up to 100,000 deaths occurred in Hungary . The cholera epidemic struck Warsaw during the November Uprising between 16 May and 20 August 1831; 4,734 people fell ill and 2,524 died. The epidemic of cholera brought to Poland and East Prussia by Russian soldiers forced Prussian authorities to close their borders to Russian transports. There were Cholera Riots in the Russian Empire caused by the government's anticholera measures. [ citation needed ] By early 1831, frequent reports of the spread of the pandemic in Russia prompted the British government to issue quarantine orders for ships sailing from Russia to British ports. By late summer, with the disease appearing more likely to spread to Britain, its board of health, in accordance with the prevailing miasma theory , issued orders recommending as a preventive the burning of "decayed articles, such as rags, cordage, papers, old clothes, hangings...filth of every description removed, clothing and furniture should be submitted to copious effusions of water, and boiled in a strong ley (lye); drains and privies thoroughly cleansed by streams of water and chloride of lime...free and continued admission of fresh air to all parts of the house and furniture should be enjoined for at least a week". Based on the reports of two English doctors who had observed the epidemic in Saint Petersburg , the board of health published a detailed description of the disease's symptoms and onset: Giddiness, sick stomach, nervous agitation, intermittent, slow, or small pulse, cramps beginning at the tops of the fingers and toes, and rapidly approaching the trunk, give the first warning. Vomiting or purging, or both these evacuations of a liquid like rice-water or whey, or barley-water, come on; the features become sharp and contracted, the eye sinks, the look is expressive of terror and wildness; the lips, face, neck, hands, and feet, and soon after the thighs, arms, and whole surface assume a leaden, blue, purple, black, or deep brown tint according to the complexion of the individual, varying in shade with the intensity of the attack. The fingers and toes are reduced in size, the skin and soft parts covering them are wrinkled, shrivelled and folded. The nails put on a bluish pearly white; the larger superficial veins are marked by flat lines of a deeper black; the pulse becomes either small as a thread, and scarcely vibrating, or else totally extinct. The skin is deadly cold and often damp, the tongue always moist, often white and loaded, but flabby and chilled like a piece of dead flesh. The voice is nearly gone; the respiration quick, irregular, and imperfectly performed. The patient speaks in a whisper. He struggles for breath, and often lays his hand on his heart to point out the seat of his distress. Sometimes there are rigid spasms of the legs, thighs, and loins. The secretion of urine is totally suspended; vomiting and purgings, which are far from being the most important or dangerous symptoms, and which in a very great number of cases of the disease, have not been profuse, or have been arrested by medicine early in the attack, succeed. It is evident that the most urgent and peculiar symptom of this disease is the sudden depression of the vital powers: proved by the diminished action of the heart, the coldness of the surface and extremities, and the stagnant state of the whole circulation. From September 1831 to January 1832, a catastrophic cholera epidemic ravaged the lower Euphrates and Tigris regions of what is now Iraq and Iran . In Shushtar , Iran, about half of the city's inhabitants died from cholera. The Mandaean community was hit particularly hard, and all of their priests died in the plague. Yahya Bihram told Julius Heinrich Petermann that there were only 1,500 Mandaean survivors after the plague. The epidemic reached Great Britain in October 1831, appearing in Sunderland , where it was carried by passengers on a ship from the Baltic. It also appeared in Gateshead and Newcastle . In London, the disease claimed 6,536 victims; in Paris, 20,000 died (out of a population of 650,000), with about 100,000 deaths in all of France. In 1832, the epidemic reached Quebec , Ontario , and Nova Scotia in Canada and Detroit and New York City in the United States. [lower-alpha 1] It reached the Pacific coast of North America between 1832 and 1834. The pandemic prompted the passage of the landmark Public Health Act 1848 ( 11 & 12 Vict. c. 63) and the Nuisances Removal and Diseases Prevention Acts, 1848 and 1849, in England. [ citation needed ] In mid-1832, 57 Irish immigrants died who had been laying a stretch of railroad called Duffy's Cut , 30 miles west of Philadelphia. They had all contracted cholera. During the second pandemic, the scientific community varied in its beliefs about the causes of cholera. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious, although doctors did not understand how it spread. The United States believed that cholera was brought by recent immigrants, specifically the Irish, and epidemiologists understand they were carrying disease from British ports. Lastly, the British thought the disease might rise from divine intervention. Norwegian poet Henrik Wergeland wrote a stage play inspired by the pandemic, which had reached Norway . In The Indian Cholera ( Den indiske Cholera , 1835), he set his play in Colonial India , lambasting the poor response to the pandemic by authorities. [ citation needed ] As a result of the epidemic, the medical community developed a major advance, the intravenous saline drip . It was developed from the work of Dr. Thomas Latta of Leith , near Edinburgh . Latta established from blood studies that a saline drip greatly improved the condition of patients and saved many lives by preventing dehydration. Latta died in 1833 of tuberculosis.

Wiki

Cholera

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

Cholera toxin

Cholera toxin (also known as choleragen and sometimes abbreviated to CTX , Ctx or CT ) is an AB5 multimeric protein complex secreted by the bacterium Vibrio cholerae . CTX is responsible for the massive, watery diarrhea characteristic of cholera infection. It is a member of the heat-labile enterotoxin family .Robert Koch , a German physician and microbiologist, was the first person to postulate the existence of cholera toxin. In 1886, Koch proposed that Vibrio cholerae secreted a substance which caused the symptoms of Cholera . Koch's postulation was proven correct by Indian microbiologist Sambhu Nath De , whom in 1951 studied and documented the effects of injecting rabbits with heat-killed cholerae bacteria. De concluded from this experiment that an endotoxin liberated upon disintegration of the bacteria was the cause of the symptoms of cholera. In 1959, De conducted another experiment, this time using a bactaria-free culture-filtrate from V. Cholera injected into the small intestines of rabbits. The resulting build up of fluid in the intestines conclusively proved the existence of a toxin. The complete toxin is a hexamer made up of a single copy of the A subunit (part A, enzymatic, P01555 ), and five copies of the B subunit (part B, receptor binding, P01556 ), denoted as AB 5 . Subunit B binds while subunit A activates the G protein which activates adenylate cyclase . The three-dimensional structure of the toxin was determined using X-ray crystallography by Zhang et al. in 1995. The five B subunits—each weighing 11 kDa , form a five-membered ring. The A subunit which is 28 kDa, has two important segments. The A1 portion of the chain (CTA1) is a globular enzyme payload that ADP-ribosylates G proteins , while the A2 chain (CTA2) forms an extended alpha helix which sits snugly in the central pore of the B subunit ring. This structure is similar in shape, mechanism, and sequence to the heat-labile enterotoxin secreted by some strains of the Escherichia coli bacterium.Cholera toxin acts by the following mechanism: First, the B subunit ring of the cholera toxin binds to GM1 gangliosides on the surface of target cells. If a cell lacks GM1, the toxin most likely binds to other types of glycans , such as Lewis Y and Lewis X , attached to proteins instead of lipids. Once bound, the entire toxin complex is endocytosed by the cell and the reduction of a disulfide bridge releases the cholera toxin A1 (CTA1) chain. The endosome is moved to the Golgi apparatus , where the A1 protein is recognized by the endoplasmic reticulum (ER) chaperone , protein disulfide isomerase . The A1 chain is then unfolded and delivered to the membrane, where Ero1 triggers the release of the A1 protein by oxidation of protein disulfide isomerase complex. As the A1 protein moves from the ER into the cytoplasm by the Sec61 channel, it refolds and avoids deactivation as a result of ubiquitination . CTA1 is then free to bind with a human partner protein called ARF6 (ADP-ribosylation factor 6); binding to Arf6 drives a change in the shape of CTA1 which exposes its active site and enables its catalytic activity. The CTA1 fragment catalyses ADP-ribosylation of the Gs alpha subunit (Gα s ) proteins using NAD . The ADP-ribosylation causes the Gα s subunit to lose its catalytic activity of GTP hydrolysis into GDP + P i , thus maintaining Gα s in its activated state. Increased Gα s activation leads to increased adenylate cyclase activity, which increases the intracellular concentration of 3',5'-cyclic AMP (cAMP) to more than 100-fold over normal and over-activates cytosolic PKA . These active PKA then phosphorylate the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel proteins, which leads to ATP -mediated efflux of chloride ions and leads to secretion of H 2 O , Na + , K + , and HCO 3 − into the intestinal lumen . In addition, the entry of Na + and consequently the entry of water into enterocytes are diminished. The combined effects result in rapid fluid loss from the intestine, up to 2 liters per hour, leading to severe dehydration and other factors associated with cholera, including a rice-water stool . The pertussis toxin (also an AB 5 protein) produced by Bordetella pertussis acts in a similar manner with the exception that it ADP-ribosylates the Gα i subunit , rendering it unable to inhibit cAMP production. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer . Virulent strains of V. cholerae (the O1 and O139 Serogroups ) hold a genes from a virus known as a CTXφ Bacteriophage . The integrated CTXφ gene contains many of the genes of RS1, a filamentous "satellite" phage, including elements for replication (RstA), integration (RstB), and regulation of gene expression (RstR), as well as genes coding for proteins needed for phage packaging and secretion (Psh, Cep, OrfU, Ace and Zot), which are very similar to the genes of Ff filamentous coliphages. These genes (and others) enable the replication and later secretion of the CTXφ bacteriophage, as well as coding for CTX, enabling the horizontal gene transfer of CTXφ to other susceptible celles. Because the B subunit appears to be relatively non-toxic, researchers have found a number of applications for it in cell and molecular biology. It is routinely used as a neuronal tracer . Treatment of cultured rodent neural stem cells with cholera toxin induces changes in the localization of the transcription factor Hes3 and increases their numbers. GM1 gangliosides are found in lipid rafts on the cell surface. B subunit complexes labelled with fluorescent tags or subsequently targeted with antibodies can be used to identify rafts. There are currently two vaccines for cholera: Dukoral and Shanchol. Both vaccines use whole killed V. cholerae cells however, Dukoral also contains recombinant cholera toxin β (rCTB). Some studies suggest that the inclusion of rCTB may improve vaccine efficacy in young children (2-10) and increase the duration of protection. This is countered by the costs of protecting and storing rCTB against degradation. Another application of the CTB subunit may be as a vaccine adjuvant to other vaccines. It has been shown that coupling CTB and antigens improves the response of the vaccine. Currently the adjuvant potential of CTB has been shown in large animal models so further research is needed. This may allow for CTB to be used as an adjuvant for vaccinating against many kinds of diseases. This may include bacterial and viral infections, allergy and diabetes. Of note, as CTB has shown to induce mucosal humoral immune responses , vaccines against mucosal viruses such as HIV are a potential target. Since cholera toxin has been shown to preferentially bind to GM1 gangliosides, this characteristic can be utilized for membrane studies. Lipid rafts are difficult to study as they vary in size and lifetime, as well being part of an extremely dynamic component of cells. Using cholera toxin β as a marker, we can get a better understanding of the properties and functions of lipid rafts. Endocytosis is broadly divided into clathrin -dependent and clathrin-independent process, and the cholera toxin utilizes both pathways. Cholera toxin has been shown to enter cells via endocytosis in multiple pathways. These pathways include caveolae , clathrin-coated pits, clathrin-independent carriers (CLICs), and GPI -Enriched Endocytic Compartments ( GEECs ) pathway, ARF6 -mediated endocytosis and Fast Endophilin-Mediated Endocytosis (FEME). How cholera toxin triggers these endocytosis pathways is not fully understood, but the fact that cholera toxin triggers these pathways shows the use of the toxin as an important marker to investigate these mechanisms. One of the most important aspects of cholera toxin is the retrograde traffic mechanism that transports the toxin from the cell membrane back to the trans-Golgi network and the endoplasmic reticulum. Since both cholera toxin and GM1 species can be tagged with a fluorescent tags, the mechanism of retrograde traffic can be monitored. This opens up the potential to monitor the mechanism in real time. This may open up new discoveries on how intracellular transport works and how protein and lipid sorting work in the endocytotic pathway . There are currently two vaccines for cholera: Dukoral and Shanchol. Both vaccines use whole killed V. cholerae cells however, Dukoral also contains recombinant cholera toxin β (rCTB). Some studies suggest that the inclusion of rCTB may improve vaccine efficacy in young children (2-10) and increase the duration of protection. This is countered by the costs of protecting and storing rCTB against degradation. Another application of the CTB subunit may be as a vaccine adjuvant to other vaccines. It has been shown that coupling CTB and antigens improves the response of the vaccine. Currently the adjuvant potential of CTB has been shown in large animal models so further research is needed. This may allow for CTB to be used as an adjuvant for vaccinating against many kinds of diseases. This may include bacterial and viral infections, allergy and diabetes. Of note, as CTB has shown to induce mucosal humoral immune responses , vaccines against mucosal viruses such as HIV are a potential target. Since cholera toxin has been shown to preferentially bind to GM1 gangliosides, this characteristic can be utilized for membrane studies. Lipid rafts are difficult to study as they vary in size and lifetime, as well being part of an extremely dynamic component of cells. Using cholera toxin β as a marker, we can get a better understanding of the properties and functions of lipid rafts. Endocytosis is broadly divided into clathrin -dependent and clathrin-independent process, and the cholera toxin utilizes both pathways. Cholera toxin has been shown to enter cells via endocytosis in multiple pathways. These pathways include caveolae , clathrin-coated pits, clathrin-independent carriers (CLICs), and GPI -Enriched Endocytic Compartments ( GEECs ) pathway, ARF6 -mediated endocytosis and Fast Endophilin-Mediated Endocytosis (FEME). How cholera toxin triggers these endocytosis pathways is not fully understood, but the fact that cholera toxin triggers these pathways shows the use of the toxin as an important marker to investigate these mechanisms. One of the most important aspects of cholera toxin is the retrograde traffic mechanism that transports the toxin from the cell membrane back to the trans-Golgi network and the endoplasmic reticulum. Since both cholera toxin and GM1 species can be tagged with a fluorescent tags, the mechanism of retrograde traffic can be monitored. This opens up the potential to monitor the mechanism in real time. This may open up new discoveries on how intracellular transport works and how protein and lipid sorting work in the endocytotic pathway . Since cholera toxin has been shown to preferentially bind to GM1 gangliosides, this characteristic can be utilized for membrane studies. Lipid rafts are difficult to study as they vary in size and lifetime, as well being part of an extremely dynamic component of cells. Using cholera toxin β as a marker, we can get a better understanding of the properties and functions of lipid rafts. Endocytosis is broadly divided into clathrin -dependent and clathrin-independent process, and the cholera toxin utilizes both pathways. Cholera toxin has been shown to enter cells via endocytosis in multiple pathways. These pathways include caveolae , clathrin-coated pits, clathrin-independent carriers (CLICs), and GPI -Enriched Endocytic Compartments ( GEECs ) pathway, ARF6 -mediated endocytosis and Fast Endophilin-Mediated Endocytosis (FEME). How cholera toxin triggers these endocytosis pathways is not fully understood, but the fact that cholera toxin triggers these pathways shows the use of the toxin as an important marker to investigate these mechanisms. One of the most important aspects of cholera toxin is the retrograde traffic mechanism that transports the toxin from the cell membrane back to the trans-Golgi network and the endoplasmic reticulum. Since both cholera toxin and GM1 species can be tagged with a fluorescent tags, the mechanism of retrograde traffic can be monitored. This opens up the potential to monitor the mechanism in real time. This may open up new discoveries on how intracellular transport works and how protein and lipid sorting work in the endocytotic pathway .

Wiki

Cholera

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

Vibrio cholerae

Vibrio cholerae is a species of Gram-negative , facultative anaerobe and comma-shaped bacteria . The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin -containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera , which can be derived from the consumption of undercooked or raw marine life species or drinking contaminated water. V. cholerae was first described by Félix-Archimède Pouchet in 1849 as some kind of protozoa. Filippo Pacini correctly identified it as a bacterium and from him, the scientific name is adopted. The bacterium as the cause of cholera was discovered by Robert Koch in 1884. Sambhu Nath De isolated the cholera toxin and demonstrated the toxin as the cause of cholera in 1959. The bacterium has a flagellum (a tail like structure)at one pole and several pili throughout its cell surface. It undergoes respiratory and fermentative metabolism. Two serogroups called O1 and O139 are responsible for cholera outbreaks. Infection is mainly through drinking contaminated water or ingestion of food contaminated with faecal matter from an infected person, therefore is linked to sanitation and hygiene. When ingested, it invades the intestinal mucosa which can cause diarrhea and vomiting in a host within several hours to 2–3 days of ingestion. Ringers lactate and Oral rehydration solution combined with antibiotics such as fluoroquinolones and tetracyclines are the common treatment methods in severe cases. V. cholerae has two circular DNA. One DNA produces the cholera toxin (CT), a protein that causes profuse, watery diarrhea (known as "rice-water stool"). But the DNA does not directly code for the toxin as the genes for cholera toxin are carried by CTXphi (CTXφ), a temperate bacteriophage (virus). The virus only produces the toxin when inserted into the bacterial DNA. Quorum sensing in V. cholerae is well studied and it activates host immune signaling and prolongs host survival, by limiting the bacterial intake of nutrients, such as tryptophan , which further is converted to serotonin . As such, quorum sensing allows a commensal interaction between host and pathogenic bacteria. During the third global pandemic of cholera (1846–1860) , there was extensive scientific research to understand the etiology of the disease. The miasma theory , which posited that infections spread through contaminated air, was no longer a satisfactory explanation. The English physician John Snow was the first to give convincing evidence in London in 1854 that cholera was spread from drinking water – a contagion, not miasma. Yet he could not identify the pathogens, which made most people still believe in the miasma origin. V. cholerae was first observed and recognized under microscope by the French zoologist Félix-Archimède Pouchet . In 1849, Pouchet examined the stool samples of four people having cholera. His presentation before the French Academy of Sciences on 23 April was recorded as: "[Pouchet] could verify that there existed in these [cholera patients] dejecta an immense quantity of microscopic infusoria ." As summarised in the Gazette medicale de Paris (1849, p 327), in a letter read at the 23 April 1849 meeting of the Paris Academy of Sciences , Pouchet announced that the organisms were infusoria , a name then used for microscopic protists , naming them as the ' Vibrio rugula of Mueller and Shrank', a species of protozoa described by Danish naturalist Otto Friedrich Müller in 1786. An Italian physician, Filippo Pacini , while investigating cholera outbreak in Florence in the late 1854, identified the causative pathogen as a new type of bacterium. He performed autopsies of corpses and made meticulous microscopic examinations of the tissues and body fluids. From feces and intestinal mucosa , he identified many comma-shaped bacilli. Reporting his discovery before the Società Medico-Fisica Fiorentina (Medico-Physician Society of Florence) on 10 December, and published in the 12 December issue of the Gazzetta Medica Italiana ( Medical Gazette of Italy ), Pacini stated: Le poche materie del vomito che ho potuto esaminare nel secondo e terzo caso di cholera ... e di più trovai degli ammassi granulosi appianati, simili a quelli che si formano alla superficie delle acque corrotte, quando sono per svilupparsi dei vibrioni; dei quali di fatto ne trovai alcuni del genere Bacterium , mentre la massima parte, per la loro estrema piccolezza, erano stati eliminati con la decantazione del fluido. [From the few samples of vomit that I was able to examine in the second and third cases of cholera ... and in addition I found smoothed granular masses, similar to those which form on the surface of dirty waters, when they are about to develop vibrios; of which in fact I found some of the genus Bacterium , while the greatest part, because of their extreme smallness, had been eliminated with the removal of the liquid. ] Pacini thus introduced the name vibrioni (Latin vībro means "to move rapidly to and fro, to shake, to agitate"). A Catalan physician Joaquim Balcells i Pascual also reported such bacterium around the same time. The discovery of the new bacterium was not regarded as medically important as the bacterium was not directly attributed to cholera. Pacini also stated that there was no reason to say that the bacterium caused the disease since he failed to create a pure culture and perform experiments, which was necessary 'to attribute the quality of contagion to cholera'. The miasma theory was still not ruled out. The medical importance and relationship between the bacterium and the cholera disease was discovered by German physician Robert Koch . In August 1883, Koch, with a team of German physicians, went to Alexandria, Egypt, to investigate the cholera epidemic there. Koch found that the intestinal mucosa of people who died of cholera always had the bacterium, yet he could not confirm if it was the causative agent. He moved to Calcutta (now Kolkata), India, where the epidemic was more severe. It was from here that he isolated the bacterium in a pure culture on 7 January 1884. He subsequently confirmed that the bacterium was a new species, and described it as "a little bent, like a comma." He reported his discovery to the German Secretary of State for the Interior on 2 February, and it was published in the Deutsche Medizinische Wochenschrift ( German Medical Weekly ). Although Koch was convinced that the bacterium was the cholera pathogen, he could not entirely procure critical evidence that the bacterium produced the symptoms in healthy subjects (an important element in what was later known as Koch's postulates ). His experiment on animals using his pure bacteria culture did not lead to the appearance of the disease in any of the subjects, and he correctly deduced that animals are immune to the human pathogen. The bacterium was by then known as "the comma bacillus." It was only in 1959, in Calcutta, that Indian physician Sambhu Nath De isolated the cholera toxin and showed that it caused cholera in healthy subjects, hence fully proving the bacterium-cholera relationship. Pacini had used the name " vibrio cholera ", without proper binomial rendering, for the name of the bacterium. Following Koch's description, a scientific name Bacillus comma was popularised. But an Italian bacteriologist Vittore Trevisan published in 1884 that Koch's bacterium was the same as that of Pacini's and introduced the name Bacillus cholerae. A German physician Richard Friedrich Johannes Pfeiffer renamed it as Vibrio cholerae in 1896. The named was adopted by the Committee of the Society of American Bacteriologists on Characterization and Classification of Bacterial Types in 1920. In 1964, Rudolph Hugh of the George Washington University School of Medicine proposed to use the genus Vibrio with the type species V. cholerae (Pacini 1854) as a permanent name of the bacterium, regardless of the same name for protozoa. It was accepted by the Judicial Commission of the International Committee on Bacteriological Nomenclature in 1965, and the International Association of Microbiological Societies in 1966. During the third global pandemic of cholera (1846–1860) , there was extensive scientific research to understand the etiology of the disease. The miasma theory , which posited that infections spread through contaminated air, was no longer a satisfactory explanation. The English physician John Snow was the first to give convincing evidence in London in 1854 that cholera was spread from drinking water – a contagion, not miasma. Yet he could not identify the pathogens, which made most people still believe in the miasma origin. V. cholerae was first observed and recognized under microscope by the French zoologist Félix-Archimède Pouchet . In 1849, Pouchet examined the stool samples of four people having cholera. His presentation before the French Academy of Sciences on 23 April was recorded as: "[Pouchet] could verify that there existed in these [cholera patients] dejecta an immense quantity of microscopic infusoria ." As summarised in the Gazette medicale de Paris (1849, p 327), in a letter read at the 23 April 1849 meeting of the Paris Academy of Sciences , Pouchet announced that the organisms were infusoria , a name then used for microscopic protists , naming them as the ' Vibrio rugula of Mueller and Shrank', a species of protozoa described by Danish naturalist Otto Friedrich Müller in 1786. An Italian physician, Filippo Pacini , while investigating cholera outbreak in Florence in the late 1854, identified the causative pathogen as a new type of bacterium. He performed autopsies of corpses and made meticulous microscopic examinations of the tissues and body fluids. From feces and intestinal mucosa , he identified many comma-shaped bacilli. Reporting his discovery before the Società Medico-Fisica Fiorentina (Medico-Physician Society of Florence) on 10 December, and published in the 12 December issue of the Gazzetta Medica Italiana ( Medical Gazette of Italy ), Pacini stated: Le poche materie del vomito che ho potuto esaminare nel secondo e terzo caso di cholera ... e di più trovai degli ammassi granulosi appianati, simili a quelli che si formano alla superficie delle acque corrotte, quando sono per svilupparsi dei vibrioni; dei quali di fatto ne trovai alcuni del genere Bacterium , mentre la massima parte, per la loro estrema piccolezza, erano stati eliminati con la decantazione del fluido. [From the few samples of vomit that I was able to examine in the second and third cases of cholera ... and in addition I found smoothed granular masses, similar to those which form on the surface of dirty waters, when they are about to develop vibrios; of which in fact I found some of the genus Bacterium , while the greatest part, because of their extreme smallness, had been eliminated with the removal of the liquid. ] Pacini thus introduced the name vibrioni (Latin vībro means "to move rapidly to and fro, to shake, to agitate"). A Catalan physician Joaquim Balcells i Pascual also reported such bacterium around the same time. The discovery of the new bacterium was not regarded as medically important as the bacterium was not directly attributed to cholera. Pacini also stated that there was no reason to say that the bacterium caused the disease since he failed to create a pure culture and perform experiments, which was necessary 'to attribute the quality of contagion to cholera'. The miasma theory was still not ruled out. The medical importance and relationship between the bacterium and the cholera disease was discovered by German physician Robert Koch . In August 1883, Koch, with a team of German physicians, went to Alexandria, Egypt, to investigate the cholera epidemic there. Koch found that the intestinal mucosa of people who died of cholera always had the bacterium, yet he could not confirm if it was the causative agent. He moved to Calcutta (now Kolkata), India, where the epidemic was more severe. It was from here that he isolated the bacterium in a pure culture on 7 January 1884. He subsequently confirmed that the bacterium was a new species, and described it as "a little bent, like a comma." He reported his discovery to the German Secretary of State for the Interior on 2 February, and it was published in the Deutsche Medizinische Wochenschrift ( German Medical Weekly ). Although Koch was convinced that the bacterium was the cholera pathogen, he could not entirely procure critical evidence that the bacterium produced the symptoms in healthy subjects (an important element in what was later known as Koch's postulates ). His experiment on animals using his pure bacteria culture did not lead to the appearance of the disease in any of the subjects, and he correctly deduced that animals are immune to the human pathogen. The bacterium was by then known as "the comma bacillus." It was only in 1959, in Calcutta, that Indian physician Sambhu Nath De isolated the cholera toxin and showed that it caused cholera in healthy subjects, hence fully proving the bacterium-cholera relationship. Pacini had used the name " vibrio cholera ", without proper binomial rendering, for the name of the bacterium. Following Koch's description, a scientific name Bacillus comma was popularised. But an Italian bacteriologist Vittore Trevisan published in 1884 that Koch's bacterium was the same as that of Pacini's and introduced the name Bacillus cholerae. A German physician Richard Friedrich Johannes Pfeiffer renamed it as Vibrio cholerae in 1896. The named was adopted by the Committee of the Society of American Bacteriologists on Characterization and Classification of Bacterial Types in 1920. In 1964, Rudolph Hugh of the George Washington University School of Medicine proposed to use the genus Vibrio with the type species V. cholerae (Pacini 1854) as a permanent name of the bacterium, regardless of the same name for protozoa. It was accepted by the Judicial Commission of the International Committee on Bacteriological Nomenclature in 1965, and the International Association of Microbiological Societies in 1966. V. cholerae is a highly motile, comma shaped, gram-negative rod. The active movement of V. cholerae inspired the genus name because "vibrio" in Latin means "to quiver". Except for V. cholerae and V. mimicus , all other vibrio species are halophilic . Initial isolates are slightly curved, whereas they can appear as straight rods upon laboratory culturing. The bacterium has a flagellum at one cell pole as well as pili . It tolerates alkaline media that kill most intestinal commensals, but they are sensitive to acid. It is a aerobe while all other Vibrios are facultative anaerobes, and can undergo respiratory and fermentative metabolism. It measures 0.3 μm in diameter and 1.3 μm in length with average swimming velocity of around 75.4 μm/sec. V. cholerae pathogenicity genes code for proteins directly or indirectly involved in the virulence of the bacteria. To adapt the host intestinal environment and to avoid being attacked by bile acids and antimicrobial peptides , V. cholera uses its outer membrane vesicles (OMVs). Upon entry, the bacteria sheds its OMVs, containing all the membrane modifications that make it vulnerable for the host attack. During infection, V. cholerae secretes cholera toxin (CT), a protein that causes profuse, watery diarrhea (known as "rice-water stool"). This cholera toxin contains 5 B subunits that plays a role in attaching to the intestinal epithelial cells and 1 A subunit that plays a role in toxin activity . Colonization of the small intestine also requires the toxin coregulated pilus (TCP), a thin, flexible, filamentous appendage on the surface of bacterial cells. Expression of both CT and TCP is mediated by two component systems (TCS), which typically consist of a membrane-bound histidine kinase and an intracellular response element. TCS enable bacteria to respond to changing environments. In V. cholerae several TCS have been identified to be important in colonization, biofilm production and virulence. Quorum regulatory small RNAs ( Qrr RNA ) have been identified as targets of V. cholerae TCS. Here, the small RNA (sRNA) molecules bind to mRNA to block translation or induce degradation of inhibitors of expression of virulence or colonization genes. In V. cholerae the TCS EnvZ/OmpR alters gene expression via the sRNA coaR in response to changes in osmolarity and pH. An important target of coaR is tcpI , which negatively regulates expression of the major subunit of the TCP encoding gene ( tcpA ). When tcpI is bound by coaR it is no longer able to repress expression tcpA , leading to an increased colonization ability. Expression of coaR is upregulated by EnvZ/OmpR at a pH of 6,5, which is the normal pH of the intestinal lumen, but is low at higher pH values. V. cholerae in the intestinal lumen utilizes the TCP to attach to the intestinal mucosa, not invading the mucosa. After doing so it secretes cholerae toxin causing its symptoms. This then increases cyclic AMP or cAMP by binding (cholerae toxin) to adenylyl cyclase activating the GS pathway which leads to efflux of water and sodium into the intestinal lumen causing watery stools or rice watery stools. V. cholerae can cause syndromes ranging from asymptomatic to cholera gravis. In endemic areas, 75% of cases are asymptomatic, 20% are mild to moderate, and 2-5% are severe forms such as cholera gravis. Symptoms include abrupt onset of watery diarrhea (a grey and cloudy liquid), occasional vomiting , and abdominal cramps. Dehydration ensues, with symptoms and signs such as thirst, dry mucous membranes, decreased skin turgor, sunken eyes, hypotension , weak or absent radial pulse , tachycardia , tachypnea , hoarse voice, oliguria , cramps, kidney failure , seizures , somnolence , coma, and death. Death due to dehydration can occur in a few hours to days in untreated children. The disease is also particularly dangerous for pregnant women and their fetuses during late pregnancy, as it may cause premature labor and fetal death. A study done by the Centers for Disease Control (CDC) in Haiti found that in pregnant women who contracted the disease, 16% of 900 women had fetal death. Risk factors for these deaths include: third trimester, younger maternal age, severe dehydration, and vomiting Dehydration poses the biggest health risk to pregnant women in countries that there are high rates of cholera. In cases of cholera gravis involving severe dehydration, up to 60% of patients can die; however, less than 1% of cases treated with rehydration therapy are fatal. The disease typically lasts 4–6 days. Worldwide, diarrhoeal disease , caused by cholera and many other pathogens, is the second-leading cause of death for children under the age of 5 and at least 120,000 deaths are estimated to be caused by cholera each year. In 2002, the WHO deemed that the case fatality ratio for cholera was about 3.95%. V. cholerae infects the intestine and causes diarrhea, the hallmark symptom of cholera. Infection can be spread by eating contaminated food or drinking contaminated water. It also can spread through skin contact with contaminated human feces. Not all infection indicate symptoms, only about 1 in 10 people develop diarrhea. The major symptoms include: watery diarrhea, vomiting, rapid heart rate, loss of skin elasticity, low blood pressure, thirst, and muscle cramps. This illness can get serious as it can progress to kidney failure and possible coma. If diagnosed, it can be treated using medications. V. cholerae has an endemic or epidemic occurrence. In countries where the disease has been for the past three years and the cases confirmed are local (within the confines of the country) transmission is considered to be "endemic." Alternatively, an outbreak is declared when the occurrence of disease exceeds the normal occurrence for any given time or location. Epidemics can last several days or over a span of years. Additionally, countries that have an occurrence of an epidemic can also be endemic. The longest standing V. cholerae epidemic was recorded in Yemen. Yemen had two outbreaks, the first occurred between September 2016 and April 2017, and the second began later in April 2017 and recently was considered to be resolved in 2019. The epidemic in Yemen took over 2,500 lives and impacted over 1 million people of Yemen. More outbreaks have occurred in Africa, the Americas, and Haiti.When visiting areas with epidemic cholera, the following precautions should be observed: drink and use bottled water; frequently wash hands with soap and safe water; use chemical toilets or bury feces if no restroom is available; do not defecate in any body of water and cook food thoroughly. Supplying proper, safe water is important. A precaution to take is to properly sanitize. Hand hygiene is an essential in areas where soap and water is not available. When there is no sanitation available for hand washing, scrub hands with ash or sand and rinse with clean water. A single dose vaccine is available for those traveling to an area where cholera is common. There is a V. cholerae vaccine available to prevent disease spread. The vaccine is known as the, "oral cholera vaccine" (OCV). There are three types of OCV available for prevention: Dukoral®, Shanchol™, and Euvichol-Plus®. All three OCVs require two doses to be fully effective. Countries who are endemic or have an epidemic status are eligible to receive the vaccine based on several criteria: Risk of cholera, Severity of cholera, WASH conditions and capacity to improve, Healthcare conditions and capacity to improve, Capacity to implement OCV campaigns, Capacity to conduct M&E activities, Commitment at national and local level Since May the start of the OCV program to May 2018 over 25 million vaccines have been distributed to countries who meet the above criteria. The basic, overall treatment for Cholera is re-hydration, to replace the fluids that have been lost. Those with mild dehydration can be treated orally with an oral rehydration solution (ORS) . When patients are severely dehydrated and unable to take in the proper amount of ORS, IV fluid treatment is generally pursued. Antibiotics are used in some cases, typically fluoroquinolones and tetracyclines . V. cholerae (and Vibrionaceae in general) has two circular chromosomes , together totalling 4 million base pairs of DNA sequence and 3,885 predicted genes . The genes for cholera toxin are carried by CTXphi (CTXφ), a temperate bacteriophage inserted into the V. cholerae genome. CTXφ can transmit cholera toxin genes from one V. cholerae strain to another, one form of horizontal gene transfer . The genes for toxin coregulated pilus are coded by the Vibrio pathogenicity island (VPI), which is separate from the prophage. The larger first chromosome is 3 Mbp long with 2,770 open reading frames (ORFs). It contains the crucial genes for toxicity, regulation of toxicity, and important cellular functions, such as transcription and translation . The second chromosome is 1 Mbp long with 1115 ORFs. It is determined to be different from a plasmid or megaplasmid due to the inclusion of housekeeping and other essential genes in the genome, including essential genes for metabolism, heat-shock proteins, and 16S rRNA genes, which are ribosomal subunit genes used to track evolutionary relationships between bacteria. Also relevant in determining if the replicon is a chromosome is whether it represents a significant percentage of the genome, and chromosome 2 is 40% by size of the entire genome. And, unlike plasmids, chromosomes are not self-transmissible. However, the second chromosome may have once been a megaplasmid because it contains some genes usually found on plasmids, including a P1 plastid-like origin of replication . CTXφ (also called CTXphi) is a filamentous phage that contains the genes for cholera toxin . Infectious CTXφ particles are produced when V. cholerae infects humans. Phage particles are secreted from bacterial cells without lysis . When CTXφ infects V. cholerae cells, it integrates into specific sites on either chromosome. These sites often contain tandem arrays of integrated CTXφ prophage . In addition to the ctxA and ctxB genes encoding cholera toxin, CTXφ contains eight genes involved in phage reproduction, packaging, secretion, integration, and regulation. The CTXφ genome is 6.9 kb long. CTXφ (also called CTXphi) is a filamentous phage that contains the genes for cholera toxin . Infectious CTXφ particles are produced when V. cholerae infects humans. Phage particles are secreted from bacterial cells without lysis . When CTXφ infects V. cholerae cells, it integrates into specific sites on either chromosome. These sites often contain tandem arrays of integrated CTXφ prophage . In addition to the ctxA and ctxB genes encoding cholera toxin, CTXφ contains eight genes involved in phage reproduction, packaging, secretion, integration, and regulation. The CTXφ genome is 6.9 kb long. The main reservoirs of V. cholerae are aquatic sources such as rivers , brackish waters , and estuaries , often in association with copepods or other zooplankton , shellfish , and aquatic plants. Cholera infections are most commonly acquired from drinking water in which V. cholerae is found naturally or into which it has been introduced from the feces of an infected person. Cholera is most likely to be found and spread in places with inadequate water treatment, poor sanitation, and inadequate hygiene. Other common vehicles include raw or undercooked fish and shellfish. Transmission from person to person is very unlikely, and casual contact with an infected person is not a risk for becoming ill. V. cholerae thrives in an aquatic environment , particularly in surface water. The primary connection between humans and pathogenic strains is through water, particularly in economically reduced areas that do not have good water purification systems. Nonpathogenic strains are also present in water ecologies. The wide variety of pathogenic and nonpathogenic strains that co-exist in aquatic environments are thought to allow for so many genetic varieties. Gene transfer is fairly common amongst bacteria, and recombination of different V. cholerae genes can lead to new virulent strains. A symbiotic relationship between V. cholerae and Ruminococcus obeum has been determined. R. obeum autoinducer represses the expression of several V. cholerae virulence factors . This inhibitory mechanism is likely to be present in other gut microbiota species which opens the way to mine the gut microbiota of members in specific communities which may utilize autoinducers or other mechanisms in order to restrict colonization by V. cholerae or other enteropathogens . Outbreaks of Cholera cause an estimated 120,000 deaths annually worldwide. There has been roughly seven pandemics since 1817, the first. These pandemics first arose in the Indian subcontinent and spread. Two serogroups of V. cholerae , O1 and O139, cause outbreaks of cholera. O1 causes the majority of outbreaks, while O139 – first identified in Bangladesh in 1992 – is confined to Southeast Asia. Many other serogroups of V. cholerae , with or without the cholera toxin gene (including the nontoxigenic strains of the O1 and O139 serogroups), can cause a cholera-like illness. Only toxigenic strains of serogroups O1 and O139 have caused widespread epidemics. V. cholerae O1 has two biotypes, classical and El Tor , and each biotype has two distinct serotypes, Inaba and Ogawa. The symptoms of infection are indistinguishable, although more people infected with the El Tor biotype remain asymptomatic or have only a mild illness. In recent years, infections with the classical biotype of V. cholerae O1 have become rare and are limited to parts of Bangladesh and India . Recently, new variant strains have been detected in several parts of Asia and Africa. Observations suggest these strains cause more severe cholera with higher case fatality rates.V. cholerae can be induced to become competent for natural genetic transformation when grown on chitin , a biopolymer that is abundant in aquatic habitats (e.g. from crustacean exoskeletons). Natural genetic transformation is a sexual process involving DNA transfer from one bacterial cell to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination . Transformation competence in V. cholerae is stimulated by increasing cell density accompanied by nutrient limitation, a decline in growth rate, or stress. The V. cholerae uptake machinery involves a competence -induced pilus , and a conserved DNA binding protein that acts as a ratchet to reel DNA into the cytoplasm. There are two models of genetic transformation, sex hypothesis and competent bacteria.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1854_Broad_Street_cholera_outbreak/html

1854 Broad Street cholera outbreak

The Broad Street cholera outbreak (or Golden Square outbreak ) was a severe outbreak of cholera that occurred in 1854 near Broad Street (now Broadwick Street ) in Soho , London , England , and occurred during the 1846–1860 cholera pandemic happening worldwide. This outbreak, which killed 616 people, is best known for the physician John Snow 's study of its causes and his hypothesis that germ-contaminated water was the source of cholera, rather than particles in the air (referred to as " miasma "). This discovery came to influence public health and the construction of improved sanitation facilities beginning in the mid-19th century. Later, the term " focus of infection " started to be used to describe sites, such as the Broad Street pump, in which conditions are favourable for transmission of an infection. Snow's endeavour to find the cause of the transmission of cholera caused him to unknowingly create a double-blind experiment .In the mid-19th century, Soho in London had a serious problem with filth due to the large influx of people and a lack of proper sanitary services: the London sewer system had not reached Soho. Cowsheds, slaughter houses and grease-boiling dens lined the streets and contributed animal droppings, rotting fluids and other contaminants to the primitive Soho sewer system. Many cellars had cesspools underneath their floorboards, which formed from the sewers and filth seeping in from the outside. Since the cesspools were overrunning, the London government decided to dump the waste into the River Thames , contaminating the water supply. London had already suffered from a "series of debilitating cholera outbreaks". These included outbreaks in 1832 and 1849 which killed a total of 14,137 people. Preceding the 1854 Broad Street cholera outbreak, physicians and scientists held two competing theories on the causes of cholera in the human body: miasma theory and germ theory. The London medical community debated between these causes for the persistent cholera outbreaks in the city. The cholera-causing bacterium Vibrio cholerae was isolated in 1854, but the finding did not become well known and accepted until decades later. Miasma theorists concluded that cholera was caused by particles in the air, or "miasmata", which arose from decomposing matter or other dirty organic sources. "Miasma" particles were thought to travel through the air and infect individuals, and thus cause cholera. Dr William Farr , the commissioner for the 1851 London census and a member of the General Register's Office, believed that miasma arose from the soil surrounding the River Thames. It contained decaying organic matter which contained miasmatic particles and was released into the London air. Miasma theorists believed in "cleansing and scouring, rather than through the purer scientific approach of microbiology". Farr later agreed with Snow's germ theory following Snow's publications. In contrast, the germ theory held that the principal cause of cholera was a germ cell that had not yet been identified. Snow theorised that this unknown germ was transmitted from person to person by individuals ingesting water. John Simon , a pathologist and the lead medical officer for London, labelled Snow's germ theory as "peculiar". Excerpt from John Simon: This doctrine is, that cholera propagates itself by a 'morbid matter' which, passing from one patient in his evacuations, is accidentally swallowed by other persons as a pollution of food or water; that an increase of the swallowed germ of the disease takes place in the interior of the stomach and bowels, giving rise to the essential actions of cholera, as at first a local derangement; and that 'the morbid matter of cholera having the property of reproducing its own kind must necessarily have some sort of structure, most likely that of a cell. Even though Simon understood Snow's theory, he questioned its relation to the cause of cholera.Miasma theorists concluded that cholera was caused by particles in the air, or "miasmata", which arose from decomposing matter or other dirty organic sources. "Miasma" particles were thought to travel through the air and infect individuals, and thus cause cholera. Dr William Farr , the commissioner for the 1851 London census and a member of the General Register's Office, believed that miasma arose from the soil surrounding the River Thames. It contained decaying organic matter which contained miasmatic particles and was released into the London air. Miasma theorists believed in "cleansing and scouring, rather than through the purer scientific approach of microbiology". Farr later agreed with Snow's germ theory following Snow's publications. In contrast, the germ theory held that the principal cause of cholera was a germ cell that had not yet been identified. Snow theorised that this unknown germ was transmitted from person to person by individuals ingesting water. John Simon , a pathologist and the lead medical officer for London, labelled Snow's germ theory as "peculiar". Excerpt from John Simon: This doctrine is, that cholera propagates itself by a 'morbid matter' which, passing from one patient in his evacuations, is accidentally swallowed by other persons as a pollution of food or water; that an increase of the swallowed germ of the disease takes place in the interior of the stomach and bowels, giving rise to the essential actions of cholera, as at first a local derangement; and that 'the morbid matter of cholera having the property of reproducing its own kind must necessarily have some sort of structure, most likely that of a cell. Even though Simon understood Snow's theory, he questioned its relation to the cause of cholera.On 31 August 1854, after several other outbreaks had occurred elsewhere in the city, a major outbreak of cholera occurred in Soho. Snow later called it "the most terrible outbreak of cholera which ever occurred in this kingdom." Over the next three days, 127 people on or near Broad Street died. During the next week, three quarters of the residents had fled the area. By 10 September, more than 500 people had died and the mortality rate was 12.8 per thousand inhabitants in some parts of the city. By the end of the outbreak, 616 people had died. Many of the victims were taken to the Middlesex Hospital , where their treatment was superintended by Florence Nightingale , who briefly joined the hospital in early September in order to help with the outbreak. According to a letter from Elizabeth Gaskell , "She herself [Nightingale] was up night and day from Friday afternoon (Sept. 1) to Sunday afternoon, receiving the poor creatures (chiefly fallen women of that neighbourhood - they had it the worst) who were being constantly brought in - - undressing them - putting on turpentine stupes, et cetera, doing it herself to as many as she could manage". By talking to local residents (with the help of Reverend Henry Whitehead ), Snow identified the source of the outbreak as the public water pump on Broad Street (now Broadwick Street ) at Cambridge Street. Although Snow's chemical and microscope examination of a sample of the water from this Broad Street pump water did not conclusively prove its danger, his facts about the patterns of illness and death among residents in Soho persuaded the St James parish authorities to disable the well pump by removing its handle. [ citation needed ] Although this action has been popularly reported as ending the outbreak, the epidemic may have already been in rapid decline, as explained by Snow: There is no doubt that the mortality was much diminished, as I said before, by the flight of the population, which commenced soon after the outbreak; but the attacks had so far diminished before the use of the water was stopped, that it is impossible to decide whether the well still contained the cholera poison in an active state, or whether, from some cause, the water had become free from it. Snow later used a dot map to illustrate how cases of cholera occurred around this pump. Snow's efforts to connect the incidence of cholera with potential geographic sources was based on creating what is now known as a Voronoi diagram . He mapped the locations of individual water pumps and generated cells which represented all the points on his map which were closest to each pump. The section of Snow's map representing areas in the city where the closest available source of water was the Broad Street pump included the highest incidence of cholera cases. Snow also performed a statistical comparison between the Southwark and Vauxhall Waterworks Company , and a waterworks at Seething Wells (owned by the Lambeth Waterworks Company ) that was further upriver and hence had cleaner water; he showed that houses supplied by the former had a cholera mortality rate 14 times that of those supplied by the latter. Regarding the decline in cases related to the Broad Street pump, Snow said: It will be observed that the deaths either very much diminished, or ceased altogether, at every point where it becomes decidedly nearer to send to another pump than to the one in Broad street. It may also be noticed that the deaths are most numerous near to the pump where the water could be more readily obtained. There was one significant anomaly—none of the workers in the nearby Broad Street brewery contracted cholera. As they were given a daily allowance of beer, they did not consume water from the nearby well. During the brewing process, the wort (or un-fermented beer) is boiled in part so that hops can be added. This step killed the cholera bacteria in the water they had used to brew with, making it safe to drink. Snow showed that the Southwark and Vauxhall Waterworks Company was taking water from sewage-polluted sections of the Thames and delivering it to homes, resulting in an increased incidence of cholera among its customers. Snow's study is part of the history of public health and health geography . It is regarded as the founding event of epidemiology . [ citation needed ] In Snow's own words: On proceeding to the spot, I found that nearly all the deaths had taken place within a short distance of the [Broad Street] pump. There were only ten deaths in houses situated decidedly nearer to another street-pump. In five of these cases the families of the deceased persons informed me that they always sent to the pump in Broad Street, as they preferred the water to that of the pumps which were nearer. In three other cases, the deceased were children who went to school near the pump in Broad Street ... With regard to the deaths occurring in the locality belonging to the pump, there were 61 instances in which I was informed that the deceased persons used to drink the pump-water from Broad Street, either constantly or occasionally ... The result of the inquiry then was, that there had been no particular outbreak or prevalence of cholera in this part of London except among the persons who were in the habit of drinking the water of the above-mentioned pump-well. I had an interview with the Board of Guardians of St. James's parish, on the evening of Thursday, the 7th September, and represented the above circumstances to them. In consequence of what I said, the handle of the pump was removed on the following day. It was discovered later that this public well had been dug 3 feet (0.9 m) from an old cesspit that had begun to leak faecal bacteria. Waste water from washing nappies , used by a baby who had contracted cholera from another source, drained into this cesspit. Its opening was under a nearby house that had been rebuilt further away after a fire and a street widening. At the time there were cesspits under most homes. Most families tried to have their raw sewage collected and dumped in the Thames to prevent their cesspit from filling faster than the sewage could decompose into the soil. [ citation needed ] At the same time, an investigation of cholera transmission was being conducted in Deptford . Around 90 people died within a few days in that town, where the water was known to be clean, and there had been no previous outbreaks of cholera. Snow was informed that the water had recently turned impure. Residents were forced to let the water run for a while before using it, in order to let the sudsy, sewer-like water run until it was clear. Snow, finding that the water the residents were using was not different from the usual water from their pump, determined that the outbreak must be caused by a leak in the pipes that allowed surrounding sewage and its contaminants to seep in to the water supply. This scenario was similar to that of the Broad Street outbreak. The incoming water was being contaminated by the increasing levels of sewage, coupled with the lack of proper and safe plumbing. After the cholera epidemic had subsided, government officials replaced the Broad Street pump handle. They had responded only to the urgent threat posed to the population, and afterwards they rejected Snow's theory. To accept his proposal would have meant indirectly accepting the oral-faecal method of transmission of disease, which was too unpleasant for most of the public to contemplate. The Broad Street outbreak was an effect rather than a cause of the epidemic. Snow's conclusions were not predominantly based on the Broad Street outbreak, as he noted that he hesitated to come to a conclusion based on a population that had predominantly fled the neighbourhood and redistributed itself. He feared throwing off results of the study. From a mathematics perspective, John Snow's innovation was focusing on death rates in areas served by two water companies which drew water from the River Thames, rather than basing it on data from victims of the Broad Street pump (which drew water from a well). Snow's work also led to a far greater health and safety impact than the removal of the Broad Street pump handle. Deactivating the pump "hardly made a dent in the citywide cholera epidemic, which went on to claim nearly 3,000 lives". Snow was sceptical of the prevailing miasma theory , which held that diseases such as cholera or the Black Death were caused by pollution or a noxious form of "bad air". The germ theory was not established at this point ( Louis Pasteur did not propose it until 1861). Snow did not understand the mechanism by which disease was transmitted, but the evidence led him to believe that it was not due to breathing foul air. Based on the pattern of illness among residents, Snow hypothesized that cholera was spread by an agent in contaminated water. He first published his theory in 1849, in an essay titled "On the Mode of Communication of Cholera". In 1855 he published a second edition, including a more elaborate investigation of the effect of the water supply in the 1854 Soho outbreak. The cholera epidemic of 1849–1854 was also related to the water supplied by companies in London at the time. The main players were the Southwark and Vauxhall Waterworks Company , and the Lambeth Waterworks Company . Both companies provided water to their customers that was drawn from the River Thames, which was highly contaminated with visible and invisible products and bacteria. Dr Hassall examined the filtered water and found it contained animal hair, among other foul substances. He made the remark that: It will be observed, that the water of the companies of the Surrey Side of London, viz., the Southwark, Vauxhall, and Lambeth, is by far the worst of all those who take their supply from the Thames Other companies, such as the New River Company and Chelsea Waterworks Company , were observed to have better filtered water; few deaths occurred in the neighbourhoods which they supplied. These two companies not only obtained their water from cleaner sources than the Thames, but they filtered the water and treated it until there were no obvious contaminants. As mentioned above, Snow is known for his influence on public health, which arose after his studies of the cholera epidemic. In attempting to figure out who was receiving impure water in each neighbourhood, what is now known as a double-blind experiment fell right into his lap. He describes the conditions of the situation in his essays: In many cases a single house has a supply different from that on either side. Each company supplies both rich and poor, both large houses and small; there is no difference in the condition or occupation of the persons receiving the water of the different companies...As there is no difference whatever either in the houses or the people receiving the supply of the two Water Companies, or in any of the physical conditions with which they are surrounded, it is obvious that no experiment could have been devised which would more thoroughly test the effect of water supply on the progress of Cholera than this, which circumstances placed ready made before the observer. The experiment too, was on the grandest scale. No fewer than three hundred thousand people of both sexes, of every age and occupation, and of every rank and station, from gentlefolks down to the very poor, were divided into two groups without their choice, and, in most cases, without their knowledge; one group being supplied water containing the sewage of London, and amongst it, whatever might have come from the cholera patients, the other group having water quite free from such impurity. Snow went on to study the water contents from each home through a test performed on each sample. In this way, it could be deduced from which supplier the home was receiving their water. He concluded that it was indeed impure water from the big companies that allowed the spread of cholera to progress rapidly. He went on to prove his theory through the observation of prisons in London, finding that cholera ceased in these places only a few days after switching to cleaner water sources. Snow's analysis of cholera and cholera outbreaks extended past the closure of the Broad Street pump. He concluded that cholera was transmitted through and affected the alimentary canal within the human body. Cholera did not affect either the circulatory or the nervous system and there was no "poison in the blood...in the consecutive fever...the blood became poisoned from urea getting into the circulation". According to Snow, this "urea" entered the blood through kidney failure. (Acute kidney failure is a complication of cholera.) Therefore, the fever was caused by kidney failure, not by a poison already present in the subject's bloodstream. Popular medical practices, such as bloodletting, could not be effective in such a case. Snow also argued that cholera was not a product of Miasma. "There was nothing in the air to account for the spread of cholera". According to Snow, cholera was spread by persons ingesting a substance, not through atmospheric transmittal. Snow cited a case of two sailors, one with cholera and one without. Eventually the second became sick as well from accidentally ingesting bodily fluids of the first. [ citation needed ]The Reverend Henry Whitehead was an assistant curate at St. Luke's church in Soho during the 1854 cholera outbreak. [ citation needed ] A former believer in the miasma theory of disease , Whitehead worked to disprove false theories. He was influenced by Snow's theory that cholera spreads by consumption of water contaminated by human waste. Snow's work, particularly his maps of the Soho area cholera victims, convinced Whitehead that the Broad Street pump was the source of the local infections. Whitehead joined Snow in tracking the contamination to a faulty cesspool and the outbreak's index case (the baby with cholera). Whitehead's work with Snow combined demographic study with scientific observation, setting an important precedent for epidemiology. The Board of Health in London had several committees, of which the Committee for Scientific Inquiries was placed in charge of investigating the cholera outbreak. They were to study the atmospheric environment in London; however, they were also to examine samples of water from several water companies in London. The committee found that the most contaminated water supply came from the South London water companies, Southwark and Vauxhall. As part of the Committee for Scientific Inquiries, Richard Dundas Thomson and Arthur Hill Hassall examined what Thomson referred to as "vibriones". Thomson examined the occurrence of vibriones in air samples from various cholera wards and Hassall observed vibriones in water samples. Neither identified vibriones as the cause of cholera. As part of their investigation of the cholera epidemic, the Board of Health sent physicians to examine in detail the conditions of the Golden Square neighbourhood and its inhabitants. The Board of Health ultimately attributed the 1854 epidemic to miasma. Dr Edwin Lankester was a physician on the local research conglomerate that studied the 1854 Broad Street Cholera Epidemic. In 1866, Lankester wrote about Snow's conclusion that the pump itself was the cause of the cholera outbreak. He agreed with Snow at the time; however, his opinion, like Snow's, was not publicly supported. Lankester subsequently closed the pump due to Snow's theory and data on the pattern of infection, and infection rates dropped significantly. Lankester eventually was named the first medical officer of health for St James's parish in London, the same area where the pump was located. A replica pump was installed in 1992 at the site of the 1854 pump. Every year the John Snow Society holds "Pumphandle Lectures" on subjects of public health. Until August 2015, when the pump was removed due to redevelopment, they also held a ceremony here in which they removed and reattached the pump handle to pay tribute to Snow's historic discovery. The original location of the historic pump is marked by a red granite paver. In addition, plaques on the John Snow pub at the corner describe the significance of Snow's findings at this site.

Wiki

Cholera

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

Love in the Time of Cholera

Love in the Time of Cholera ( Spanish : El amor en los tiempos del cólera ) is a novel written in Spanish by Colombian Nobel Prize -winning author Gabriel García Márquez and published in 1985. Edith Grossman 's English translation was published by Alfred A. Knopf in 1988.The main characters of the novel are Florentino Ariza and Fermina Daza. Florentino and Fermina fall in love in their youth. A secret relationship blossoms between the two with the help of Fermina's Aunt Escolástica. They exchange love letters. But once Fermina's father, Lorenzo Daza, finds out about the two, he forces his daughter to stop seeing Florentino immediately. When she refuses, he and his daughter move in with his deceased wife's family in another city. Regardless of the distance, Fermina and Florentino continue to communicate via telegraph. Upon her return, Fermina realizes that her relationship with Florentino was nothing but a dream since they are practically strangers; she breaks off her engagement to Florentino and returns all his letters. A young and accomplished national hero, Dr. Juvenal Urbino, meets Fermina and begins to court her. Despite her initial dislike of Urbino, Fermina gives in to her father's persuasion and the security and wealth Urbino offers, and they wed. Urbino is a physician devoted to science, modernity, and "order and progress". He is committed to the eradication of cholera and to the promotion of public works. He is a rational man whose life is organized precisely and who greatly values his importance and reputation in society. He is a herald of progress and modernization. Even after Fermina's engagement and marriage, Florentino swore to stay faithful and wait for her; but his promiscuity gets the better of him and he has hundreds of affairs. Even with all the women he is with, he makes sure that Fermina will never find out. Meanwhile, Fermina and Urbino grow old together, going through happy years and unhappy ones and experiencing all the reality of marriage. Urbino proves in the end not to have been an entirely faithful husband, confessing one affair to Fermina many years into their marriage. Though the novel seems to suggest that Urbino's love for Fermina was never as spiritually chaste as Florentino's was, it also complicates Florentino's devotion by cataloging his many trysts as well as a few potentially genuine loves. As an elderly man, Urbino attempts to get his pet parrot out of his mango tree, only to fall off the ladder he was standing on and die. After the funeral Florentino proclaims his love for Fermina once again and tells her he has stayed faithful to her all these years. Hesitant at first because she is only recently widowed, and finding his advances untoward, Fermina comes to recognize Florentino's wisdom and maturity. She eventually gives him a second chance, and their love is allowed to blossom during their old age. They go on a steamship cruise up the river together.Fermina Daza – Florentino Ariza's object of affection, and wife of Dr. Urbino, very beautiful and intelligent. Dr. Juvenal Urbino – highly respected, wealthy doctor and husband of Fermina Daza. Florentino Ariza – businessman who is in love with Fermina Daza. Lorenzo Daza – Fermina Daza's father, a mule driver; he despised Florentino and forced him to stop meeting Fermina. He is revealed to have been involved in some illicit businesses to build his fortune. Jeremiah de Saint-Amour – The man whose suicide is introduced as the opening to the novel; a photographer and chess-player. Aunt Escolástica – The woman who attempts to aid Fermina in her early romance with Florentino by delivering their letters for them. She is ultimately sent away by Lorenzo Daza for this. Tránsito Ariza – Florentino's mother. Hildebranda Sánchez – Fermina's cousin. Miss Barbara Lynch – The woman with whom Urbino confesses having had an affair, the only one during his long marriage. Leona Cassiani – She starts out as the "personal assistant" to Uncle Leo XII at the R.C.C., the company which Florentino eventually controls. At one point, it is revealed that the two share a deep respect, possibly even love, for each other, but will never actually be together. She has a maternal love for him as a result of his "charity" in rescuing her from the streets and giving her a job. Diego Samaritano – The captain of the riverboat on which Fermina and Florentino ride at the end of the novel. América Vicuña – The 14-year-old girl who toward the end of the novel is sent to live with the elderly Florentino; he is her guardian while she is in school. They have a sexual relationship, and after being rejected by Florentino and failing her exams, she kills herself. Her grooming and subsequent suicide provides a counterpoint to the novel's grand romantic themes.The story occurs mainly in an unnamed port city somewhere near the Caribbean Sea and the Magdalena River in Colombia. While the city remains unnamed throughout the novel, descriptions and names of places suggest it is based on an amalgam of Cartagena and the nearby city of Barranquilla . The fictional city is divided into such sections as "The District of the Viceroys" and "The Arcade of the Scribes". The novel takes place approximately between 1880 and the early 1930s. The city's "steamy and sleepy streets, rat-infested sewers, old slave quarter, decaying colonial architecture, and multifarious inhabitants" are mentioned variously in the text and mingle in the lives of the characters. Some critics choose to consider Love in the Time of Cholera as a sentimental story about the enduring power of true love. Others criticize this opinion as being too simple. This is manifested by Ariza's excessively romantic attitude toward life, and his gullibility in trying to retrieve the sunken treasure of a shipwreck . It is also made evident by the fact that society in the story believes that Fermina and Juvenal Urbino are perfectly happy in their marriage, while the reality of the situation is not so ideal. Critic Keith Booker compares Ariza's position to that of Humbert Humbert in Vladimir Nabokov 's Lolita , saying that just as Nabokov's Humbert, despite being a "pervert, a rapist, and a murderer," is able to charm the reader into sympathizing with his situation with his first-person account, Márquez's Ariza is able to garner the reader's sympathy, even though the reader is reminded repeatedly of his more sinister exploits through the charming third-person narration. The term cholera as it is used in Spanish, cólera , can also denote passion or human rage and ire in its feminine form. (The English adjective choleric has the same meaning.) Considering this meaning, the title is a pun: cholera as the disease, and cholera as passion, which raises the central question of the book: is love helped or hindered by extreme passion? The two men can be contrasted as the extremes of passion: one having too much, one too little; the central question of which is more conducive to love and happiness becomes the specific, personal choice that Fermina faces through her life. Florentino's passionate pursuit of nearly countless women stands in contrast to Urbino's clinical discussion of male anatomy on their wedding night. Urbino's eradication of cholera in the town takes on the additional symbolic meaning of ridding Fermina's life of rage, but also the passion. [ citation needed ] It is this second meaning to the title that manifests itself in Florentino's hatred for Urbino's marriage to Fermina, as well as in the social strife and warfare that serves as a backdrop to the entire story. [ citation needed ] Jeremiah Saint-Amour's death inspires Urbino to meditate on his own death, and especially on the infirmities that precede it. It is necessary for Fermina and Florentino to transcend not only the difficulties of love but also the societal opinion that love is a young person's prerogative (not to mention the physical difficulties of love when one is older). Some critics choose to consider Love in the Time of Cholera as a sentimental story about the enduring power of true love. Others criticize this opinion as being too simple. This is manifested by Ariza's excessively romantic attitude toward life, and his gullibility in trying to retrieve the sunken treasure of a shipwreck . It is also made evident by the fact that society in the story believes that Fermina and Juvenal Urbino are perfectly happy in their marriage, while the reality of the situation is not so ideal. Critic Keith Booker compares Ariza's position to that of Humbert Humbert in Vladimir Nabokov 's Lolita , saying that just as Nabokov's Humbert, despite being a "pervert, a rapist, and a murderer," is able to charm the reader into sympathizing with his situation with his first-person account, Márquez's Ariza is able to garner the reader's sympathy, even though the reader is reminded repeatedly of his more sinister exploits through the charming third-person narration. The term cholera as it is used in Spanish, cólera , can also denote passion or human rage and ire in its feminine form. (The English adjective choleric has the same meaning.) Considering this meaning, the title is a pun: cholera as the disease, and cholera as passion, which raises the central question of the book: is love helped or hindered by extreme passion? The two men can be contrasted as the extremes of passion: one having too much, one too little; the central question of which is more conducive to love and happiness becomes the specific, personal choice that Fermina faces through her life. Florentino's passionate pursuit of nearly countless women stands in contrast to Urbino's clinical discussion of male anatomy on their wedding night. Urbino's eradication of cholera in the town takes on the additional symbolic meaning of ridding Fermina's life of rage, but also the passion. [ citation needed ] It is this second meaning to the title that manifests itself in Florentino's hatred for Urbino's marriage to Fermina, as well as in the social strife and warfare that serves as a backdrop to the entire story. [ citation needed ]Jeremiah Saint-Amour's death inspires Urbino to meditate on his own death, and especially on the infirmities that precede it. It is necessary for Fermina and Florentino to transcend not only the difficulties of love but also the societal opinion that love is a young person's prerogative (not to mention the physical difficulties of love when one is older). The novel received critical acclaim. The literary critic Michiko Kakutani praised the book in a review for The New York Times , saying: "Instead of using myths and dreams to illuminate the imaginative life of a people as he's done so often in the past, Mr. Garcia Marquez has revealed how the extraordinary is contained in the ordinary ... The result is a rich, commodious novel, a novel whose narrative power is matched only by its generosity of vision." The writer Thomas Pynchon , also for The New York Times , argued: "This novel is also revolutionary in daring to suggest that vows of love made under a presumption of immortality – youthful idiocy, to some – may yet be honored, much later in life when we ought to know better, in the face of the undeniable. ... There is nothing I have read quite like this astonishing final chapter, symphonic, sure in its dynamics and tempo, moving like a riverboat too ... at the very best it results in works that can even return our worn souls to us, among which most certainly belongs Love in the Time of Cholera , this shining and heartbreaking novel." Stone Village Pictures bought the movie rights from the author for US$3 million, and Mike Newell was chosen to direct it, with Ronald Harwood writing the script. Filming started in Cartagena, Colombia , during September 2006. The $50 million film, the first major foreign production filmed in the scenic walled city in twenty years, was released on November 16, 2007, by New Line Cinema . On his own initiative, García Márquez persuaded singer Shakira , who is from the nearby city of Barranquilla , to provide two songs for the film.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2022–2024_Southern_Africa_cholera_outbreak/html

2022–2024 Southern Africa cholera outbreak

The 2022–2024 Southern Africa cholera outbreak is an outbreak that has spread across Southern Africa. It started in Machinga District in Malawi in March 2022. The cholera outbreak in Malawi linked to cases in South Africa , the strains belong to the seventh cholera pandemic . Rather than being a resurgence of a previously circulating strain in Africa, these cases likely resulted from the introduction of a new cholera agent from South Asia into Africa. In March 2022, Malawi recorded its first cases of cholera . In January 2024, it was reported that around 300 people had died following a cholera outbreak in Zambia . Source:

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1846–1860_cholera_pandemic/html

1846–1860 cholera pandemic

The third cholera pandemic (1846–1860) was the third major outbreak of cholera originating in India in the 19th century that reached far beyond its borders, which researchers at University of California, Los Angeles (UCLA) believe may have started as early as 1837 and lasted until 1863. In the Russian Empire , more than one million people died of cholera . In 1853–1854, the epidemic in London claimed over 10,000 lives, and there were 23,000 deaths for all of Great Britain . This pandemic was considered to have the highest fatalities of the 19th-century epidemics. It had high fatalities among populations in Asia, Europe, Africa and North America. In 1854, which was considered the worst year, 23,000 people died in Great Britain. That year, the British physician John Snow , who was working in a poor area of London, identified contaminated water as the means of transmission of the disease. After the 1854 Broad Street cholera outbreak he had mapped the cases of cholera in the Soho area in London, and noted a cluster of cases near a water pump in one neighborhood. To test his theory, he convinced officials to remove the pump handle, and the number of cholera cases in the area immediately declined. His breakthrough helped eventually bring the epidemic under control. Snow was a founding member of the Epidemiological Society of London , formed in response to a cholera outbreak in 1849, and he is considered one of the fathers of epidemiology . The second cholera pandemic spread from India, surging outward to all of Europe and northern Africa, then crossing the Atlantic to Canada and the United States, spreading to Mexico and the Caribbean. Many sources differ regarding when the second pandemic ended, and the third pandemic began. There are sources that maintain that the third cholera pandemic started with a surge from Bengal in 1839. Over 15,000 people died of cholera in Mecca in 1846. In Russia , between 1847 and 1851, more than one million people died in the country's epidemic. A two-year outbreak began in England and Wales in 1848, and claimed 52,000 lives. In London, it was the worst outbreak in the city's history, claiming 14,137 lives, over twice as many as the 1832 outbreak. Cholera hit Ireland in 1849 and killed many of the Irish Famine survivors, already weakened by starvation and fever. In 1849, cholera claimed 5,308 lives in the major port city of Liverpool , England , an embarkation point for immigrants to North America, and 1,834 in Hull , England. In 1849, a second major outbreak occurred in Paris. Cholera, believed spread from Irish immigrant ship(s) from England to the United States , spread throughout the Mississippi river system , killing over 4,500 in St. Louis and over 3,000 in New Orleans . Thousands died in New York , a major destination for Irish immigrants. The outbreak that struck Nashville in 1849–1850 took the life of former U.S. President James K. Polk . During the California Gold Rush , cholera was transmitted along the California , Mormon and Oregon Trails as 6,000 to 12,000 are believed to have died on their way to Utah and Oregon in the cholera years of 1849–1855. It is believed cholera claimed more than 150,000 victims in the United States during the two pandemics between 1832 and 1849, and also claimed 200,000 victims in Mexico . In Vietnam, cholera outbreak in 1849 killed estimatedly from 800,000 to one million people (8–10% of the kingdom's 1847 population). In Siam, cholera outbreak which started from Penang before passing to Pattani, Songkla, Samut Prakarn, Bangkok, Pathum Thani, Phitsanuloke and Ang Sila from June to July 1849 had killed at least 5,457 people in Bangkok and the estimated number of death from cholera outbreak varied from 15000 to 40000 people. The cholera epidemic in Russia that started in 1847 lasted until 1851, killing over one million people. In 1851, a ship coming from Cuba carried the disease to Gran Canaria . It is considered that more than 6,000 people died in the island during summer, out of a population of 58,000. In 1852, cholera spread east to Indonesia, and later was carried to China and Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal contributed to transmission of the disease by travelers and troops to Iran , Iraq , Arabia and Russia. Japan suffered at least seven major outbreaks of cholera between 1858 and 1902. Between 100,000 and 200,000 people died of cholera in Tokyo in an outbreak in 1858–60. In 1854, an outbreak of cholera in Chicago took the lives of 5.5 percent of the population (about 3,500 people). Providence, Rhode Island suffered an outbreak so widespread that for the next thirty years, 1854 was known there as "The Year of Cholera." In 1853–54, London's epidemic claimed 10,739 lives. In Spain , over 236,000 died of cholera in the epidemic of 1854–55 . The disease reached South America in 1854 and 1855, with victims in Venezuela and Brazil. During the third pandemic, Tunisia, which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. Some United States scientists began to believe that cholera was somehow associated with African Americans, as the disease was prevalent in the South in areas of black populations. Current researchers note their populations were underserved in terms of sanitation infrastructure, and health care, and they lived near the waterways by which travelers and ships carried the disease. The events surrounding the cholera pandemic in Bologna in 1855 were described by the city's Sanitation Department or Delegation, published in 1857. The treatise also describes prior plagues afflicting the city. The 1854 Broad Street cholera outbreak was a severe outbreak of cholera that occurred in 1854 near Broad Street (now Broadwick Street ) in the Soho district of London , England , and occurred during the third cholera pandemic. This outbreak, which killed 616 people, is best known for the physician John Snow 's study of its causes and his hypothesis that germ-contaminated water was the source of cholera , rather than particles in the air (referred to as " miasma "). Snow identified the source of an 1854 cholera outbreak as the public water pump on Broad Street (now Broadwick Street ). Although his studies were not entirely conclusive, his advocacy convinced the local council to disable the Broad Street pump by removing its handle. Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases, showing that water was being delivered to the outbreak area from sewage-polluted sections of the Thames , leading to an increased incidence of cholera. Snow's study was a major event in the history of public health and geography. It is regarded as one of the founding events of the science of epidemiology . This discovery came to influence public health and the construction of improved sanitation facilities beginning in the mid-19th century. Later, the term " focus of infection " would be used to describe sites, such as the Broad Street pump, in which conditions are good for transmission of an infection. John Snow's endeavor to find the cause of the transmission of cholera caused him to unknowingly create a double-blind experiment .The 1854 Broad Street cholera outbreak was a severe outbreak of cholera that occurred in 1854 near Broad Street (now Broadwick Street ) in the Soho district of London , England , and occurred during the third cholera pandemic. This outbreak, which killed 616 people, is best known for the physician John Snow 's study of its causes and his hypothesis that germ-contaminated water was the source of cholera , rather than particles in the air (referred to as " miasma "). Snow identified the source of an 1854 cholera outbreak as the public water pump on Broad Street (now Broadwick Street ). Although his studies were not entirely conclusive, his advocacy convinced the local council to disable the Broad Street pump by removing its handle. Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases, showing that water was being delivered to the outbreak area from sewage-polluted sections of the Thames , leading to an increased incidence of cholera. Snow's study was a major event in the history of public health and geography. It is regarded as one of the founding events of the science of epidemiology . This discovery came to influence public health and the construction of improved sanitation facilities beginning in the mid-19th century. Later, the term " focus of infection " would be used to describe sites, such as the Broad Street pump, in which conditions are good for transmission of an infection. John Snow's endeavor to find the cause of the transmission of cholera caused him to unknowingly create a double-blind experiment .

Wiki

Cholera

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

Seventh cholera pandemic

The seventh cholera pandemic is the seventh major outbreak of cholera beginning in 1961 and continuing to the present. Cholera has become endemic in many countries. In 2017, WHO announced a global strategy aiming to end the pandemic by 2030. This pandemic is based on the strain called El Tor ; it started in Indonesia in 1961 and spread to East Pakistan (now Bangladesh ), by 1963. It went to India in 1964, and into the Soviet Union by 1966. In July 1970, there was an outbreak in Odessa (now Ukraine) and in 1972 there were reports of outbreaks in Baku , but the Soviet Union suppressed this information. Cholera reached Italy in 1973 from North Africa . Japan and the South Pacific saw a few outbreaks by the late 1970s. In 1971, the number of cases reported worldwide was 155,000. But in 1991, it reached 570,000. The spread of the disease was helped by modern transportation and mass migrations. Mortality rates, however, dropped markedly as governments began modern curative and preventive measures. The usual mortality rate of 50% dropped to 10% by the 1980s and less than 3% by the 1990s. In 1991, the strain made a comeback in Latin America . It began in Peru, where it killed roughly 10,000 people. Research has traced the origin of the strain to the seventh cholera pandemic. Researchers initially suspected the strain came to Latin America through Asia from contaminated water, but samples from Latin America and samples from Africa were found to be identical. This rapid transmission of the pathogen around the globe in the 20th century can be attributed chiefly to the major hub, the Bay of Bengal , from where the disease spread. Cholera is caused by eating food or drinking water that is contaminated with the bacteria V. cholerae . It affects both children and adults, causing severe watery diarrhea with dehydration . But, as noted, the El Tor strain has persisted for decades to the present, causing repeated epidemics in varied locations, with 570,000 cases in 1991 alone. WHO and other authorities believe that the seventh pandemic continues.Cholera is an acute diarrhoeal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae . Most commonly the contamination of food or water occurs via faecal matter , and the infection is spread through the faecal-oral route . Cholera has also been found to be caused by eating raw shellfish . Symptoms of the disease appear between 12 hours and 5 days of infection; however, only 10% of infected people show severe symptoms of watery diarrhoea, vomiting and leg cramps. Cholera is diagnosed through a stool test or rectal swab, and today treatment takes the form of an oral rehydration solution (ORS). The ORS uses equimolar concentrations of sodium and glucose to maximise sodium uptake in the small intestine , and carefully replaces fluid losses. In severe cases, the rapid loss of bodily fluids leads to dehydration and patients are at risk of shock . This requires administration of intravenous fluids and antibiotics . The transmission of cholera is closely linked to inadequate access to clean water and sanitation facilities and hence, people at risk largely live in slums and poor communities. The 7th pandemic is traced to early 1961 and is ongoing. The evolution of the classical cholera strain known from the first six pandemics was revealed through genetic analysis . The first observation of the new lineage came from a laboratory in El Tor, Egypt , in 1897. By this time, the 'El Tor' strain differed from its relatives by 30%. It originated in South-Asia , then transitioned to its non-pathogenic form in the Middle East in 1900. Sometime between 1903 and 1908, the El Tor strain picked up DNA that triggered its ability to cause disease in humans. Hence, it had mutated into the El Tor pandemic strain. Makassar, South Sulawesi was the source of a 1960 outbreak of the El Tor strain, where it gained new genes that likely increased transmissibility. Cholera spread overseas in 1961, indicating a pandemic strain. Many studies point to Indonesia as the source of the seventh cholera pandemic; however, research has indicated that outbreaks in China between 1960 and 1990 were associated with the same sub-lineages. These strains spread globally from the Bay of Bengal on multiple occasions. China has been classified as both a sink and source during the pandemic spread of cholera throughout the 1960s and 1970s. The suggestion that the pandemic spread of cholera may have been augmented by Chinese cases, in addition to China being identified as an origin for bordering countries, contrasts with the view that the pandemic began in Indonesia. The El Tor cholera outbreak was first reported in Java , a seaside community near Kendal which was visited by travellers from Makassar in May 1961. Shortly after, Semarang and Djakarta became infected in June. [ citation needed ] The disease was carried into Kuching , Sarawak when boats from Celebes participated in a regatta in Kuching; the first cholera cases appeared on 1 July. This outbreak lasted two weeks, infecting 582 persons with 79 deaths (17% mortality). By August, the outbreak had reached Kalimantan and Macau (13 patients and six deaths). The first case in Hong Kong appeared on 15 August in a community near Kwangtung, a fishing area. The second case was from a boat-dwelling population located between Kwangtung and Hong Kong. Hong Kong had 72 cases with 15 deaths (20.8% mortality). By February 1, 1962, 4,107 people were infected with cholera, with 897 deaths (21.8% mortality). By September, despite a massive vaccination campaign, cholera had rapidly moved through the Philippines , where the number of infected people reached 15,000 by March 1962, with 2,005 deaths. In the Philippines alone, mortality reached 1,682 in 1962. It was reintroduced into British Borneo , supposedly by an asymptomatic traveller from Jolo Island . Outbreaks subsequently occurred in Cambodia , Thailand , Singapore and India . In 1963, WHO declared that cholera remained the number-one killer in diseases subject to international quarantine , having been reported in Taiwan , Pakistan , Afghanistan , Iran , Southern Russia , Iraq , Korea , Burma, Cambodia , South Vietnam , Malaysia , Singapore , Nepal , Thailand , Uzbekistan and Hong Kong . The mid-60s saw cholera infiltrate Southeast Asia, with outbreaks in Chittagong , Bangladesh, Cambodia, Thailand and Malaysia, and India in 1964. The El Tor strain moved further westward, invading South Asia in 1965, including Pakistan , Nepal , Afghanistan , Iran and part of Uzbek SSR . Iran, which had been free from cholera since 1939, reported 2,704 cases by mid-October. When these outbreaks occurred in Iran, the Pasteur Institute of Iran produced 9.5 million cholera vaccines to protect the population of the eastern regions of Iran. In 1966 Iraq reported its first case. The cholera strain reached the Middle East and Africa in 1970 and spread rapidly. It is thought that a traveler returning from Asia or the Middle East introduced the disease into Africa. The Arabian Peninsula, Syria and Jordan became infected, followed by Guinea in August 1970. Cholera was first thought to have spread along waterways along the coast and into the interior along the rivers . In November 1970 infected individuals seemed to travel by modernised rapid transport. This allowed cholera to extend 1,000 km, when it appeared in Mopti, Mali . Subsequently, customary large gatherings of people facilitated the outward radiation of cholera. From 1970 to 1971, Sierra Leone, Liberia, Côte d'Ivoire, Ghana, Togo, Benin, Nigeria and southern Cameroon, experienced outbreaks. The west-African outbreak of cholera during 1970–1971 infected more than 400,000 persons. Africa had a high cholera fatality rate of 16% by 1962. 25 countries were infected by the end of 1971 and, between 1972 and 1991, cholera spread throughout much of the remainder of Africa. An international campaign began in 1970, including the research laboratory in Dhaka , Bangladesh; the Southeast Asia Treaty Organisation (SEATO), the United Kingdom, Australia, and various American agencies. Human volunteers took part in an NIH -sponsored series of tests to develop an effective cholera vaccine. At this time, new outbreaks of cholera were occurring in Egypt, South Korea, and the Soviet Union. The 1964 invention of use of oral rehydration salts (ORS) to treat cholera was endorsed by WHO in the 1980s. This practice of replacing fluids and electrolytes is estimated to have saved the lives of 40 million individuals infected with cholera. As a result of the success of ORS treatment, the past 30 years have seen changes to cholera response that centred on treating affected individuals in the short term, and attempting to provide safe water and improved hygiene in the long term. The cholera pandemic beginning in 1962 is identified through the 'El Tor' biotype, and considerable research has been undertaken into this specific strain of cholera. The El Tor biotype has been demonstrated to have increased resistance to the environment. This has heightened the risk of unknowing transmission from asymptomatic carriage in humans, as opposed to the classical biotype that caused the first six cholera pandemics. [ citation needed ] Previously, health workers who were against the administration of the cholera vaccine based their opinion on the view that always limited resources should be directed at immediate rehydration and improved practices, and longer-term investment to provide safe water and improved sanitation. Such practices as appropriately cooking food before consumption, using sterilised water, following general personal hygiene, and sanitising environments, decrease the spread of cholera. In the 21st century, cholera control activities have typically still been focused on emergency responses to outbreaks, with limited attention to the underlying causes that can prevent recurrence. But, the development of new and improved cholera vaccines has allowed this practice of emergency responses to be revised. In addition, recent research has advanced understanding of cholera, its transmission and the immune response . Subsequently, these advances have resulted in the development of experimental cholera vaccines derived from non-living and attenuated live strains. By 2017 the FDA had approved a single-dose, live, oral cholera vaccine called Vaxchora for adults aged 18–64 who are travelling to an area of active cholera transmission. A study in Haiti has shown lasting protection from a two-dose cholera vaccine. During the 2010–2017 cholera outbreak in Haiti, those who received the two doses of the vaccine were 76% less likely to become sick. This protection lasted 4 years. [ citation needed ] The clinical severity of the El Tor biotype causing pandemic cholera in 1962, also resulted in modern research assessing administration of antimicrobials in the initial phase of an outbreak. This was tested in the 1970s with tetracycline but was found not to be useful due to resistance against this antibiotic . Questions have been raised alluding to newer drugs, and whether the administration of these will be more useful than such previous attempts. The ongoing seventh pandemic has affirmed that cholera is still prevalent in society and can cause high mortality. In 1992 the Global Task Force on Cholera Control (GTFCC) was organized to coordinate activities and support countries after a severe cholera outbreak in Peru. Today it consists of more than 30 collaborating institutions, including NGOs, academic institutions, and UN agencies supporting affected countries. In 2017 they convened a high-level meeting with officials from cholera-affected countries, donors, and technical partners to announce their strategy "The Global Roadmap to 2030", an initiative to end cholera as a threat to public health by 2030. The three components of the strategy are: "early detection and quick response to contain the outbreaks; a multi-sectorial {sic} approach to prevent cholera recurrence, and, coordination of technical support and advocacy, resource mobilisation and partnership at the global level.

Wiki

Cholera

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

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.

Wiki

Cholera

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

Cholera riots

Cholera riots are civil disturbances associated with an outbreak or epidemic of cholera .Cholera riots ( Холерные бунты in Russian ) broke out among the urban population, peasants and soldiers in 1830–1831 when the second cholera pandemic reached Russia . The riots were caused by the anti-cholera measures, undertaken by the tsarist government, such as quarantine , armed cordons and migratory restrictions. Influenced by rumors of deliberate contamination of ordinary people by government officials and doctors, agitated mobs started raiding police departments and state hospitals, killing hated functionaries, officers, landowners and gentry. In November 1830, the citizens of Tambov attacked their governor , but they were soon suppressed by the regular army . In June 1831, there was a riot on the Sennaya Square in St.Petersburg , but the agitated workers, artisans and house-serfs were dispersed by the army, reinforced with artillery . The riots went especially out of control in Sevastopol and in military settlements of the Novgorod guberniya . The rebels established their own court , electoral committees out of soldiers and non-commissioned officers and conducted propaganda among the serfs. Further cholera riots in 1892 were aggressively suppressed by the tsarist government. On August 29, 1909 The New York Times reported more cholera riots in Russia. Asiatic cholera reached Britain in 1831 from Russia, beginning in Sunderland and heading north to Aberdeen . A major riot took place in Aberdeen on 26 December 1831, when a dog dug up a dead body in the city. 20,000 Aberdonians (two-thirds of the city's population, although this number has been criticised as an exaggeration) protested against the medical establishment, which they believed were using the epidemic as a body-snatching scheme similar to the Burke and Hare murders of 1828: A cry was raised of 'Burn the house; down with the burking shop'. Shavings, fir, tar, barrels and staves, were quickly procured and lighted, and within five minutes the back wall fell down with a tremendous crash. The building was completely destroyed, and had not the mob been kept in check by the sight of the military ... other acts of violence would, no doubt, have been committed. Three men were brought to trial for riotous behaviour, and sentenced to jail in Aberdeen for twelve months, with the judge placing blame on the medical profession for its gross negligence in dealing with the disease. The main epidemic in Britain occurred a year later. There was widespread public fear, and the political and medical response to the disease was variable and inadequate. In the summer of 1832, a series of cholera riots occurred in various towns and cities throughout Britain, frequently directed against the authorities, doctors, or both. 72 cholera riots occurred throughout the British Isles , 14 of which made reference to body-snatchers ("Burkers"). Anatomical schools were not specifically targeted, although individual physicians and hospitals were, as they saw the medical authorities as acting in coordination with the state to purposefully kill and reduce the population of the poor and "[weed] out the weak"; a doctor in Ballyshannon said that the crowds believed that "the doctors ... were to have 10 guineas a day: £5 of every one they killed; and to poison without mercy." The city of Liverpool experienced more riots than elsewhere. Between 29 May and 10 June 1832, eight major street riots occurred, with several other minor disturbances. The object of the crowd's anger was the local medical fraternity. The public perception was that cholera victims were being removed to the hospital to be killed by doctors in order to use them for anatomical dissection. "Bring out the Burkers" was one cry of the Liverpool mobs. This issue was of special concern to the Liverpool citizenry because in 1826, thirty-three bodies had been discovered on the Liverpool docks, about to be shipped to Scotland for dissection. Two years later a local surgeon, William Gill, was tried and found guilty of running an extensive local grave robbing system to supply corpses for his dissection rooms. The widespread cholera rioting in Liverpool was thus as much related to local anatomical issues as it was to the national epidemic. The riots ended relatively abruptly, largely in response to an appeal by the Roman Catholic clergy read from church pulpits, and also published in the local press. In addition, a respected local doctor, James Collins, published a passionate appeal for calm. The Liverpool Cholera Riots of 1832 demonstrate the complex social responses to epidemic disease, as well as the fragile interface between the public and the medical profession. In the same year, riots were reported in Exeter as people objected to the burial of cholera-infected bodies in local graveyards. Gravediggers were attacked. The local authorities had instituted regulations for the disposal of cholera-infected corpses and their clothes and bedding. Even the collection of clothing could result in riot or disorder as family and friends argued over the amount of compensation to be paid.In July 1831, a cholera uprising [ sk ] of 40,000 peasants broke out in the territory of Upper Hungary (today's eastern Slovakia ) in more than 150 villages and small towns. In 1893 fatal riots broke out in Hamburg , Germany during the fifth cholera pandemic , because the public objected to sanitary officers trying to enforce regulations for the prevention of spread of the disease. The crowd beat to death a sanitary officer and one of the policemen sent to protect them. Troops were called out and dispersed the crowd with fixed bayonets.In December 2008, baton-wielding riot police broke up protests in Harare and detained dozens, as the death toll of a cholera epidemic neared 600 in Zimbabwe 's worsening health and economic crises. Trade unionists protesting against limits on cash withdrawals were beaten by security forces in Harare, while police also dispersed doctors and nurses who tried to hand in a petition against the collapse of the health system.

Wiki

Cholera

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

Cholera pit

A cholera pit was a burial place used in a time of emergency when the disease was prevalent. Such mass graves were often unmarked and were placed in remote or specially selected locations. Public fears of contagion, lack of space within existing churchyards and restrictions placed on the movements of people from location to location also contributed to their establishment and use. Many of the victims were poor and lacked the funds for memorial stones, however memorials were sometimes added at a later date. Often the bodies of cholera victims were wrapped in cotton or linen and doused in coal-tar or pitch before placing into a coffin. Each burial was in a pit 8 feet (2.4 m) deep and liberally sprinkled with quicklime . The bodies were sometimes burnt before interment. It is considered that the cholera risk posed through disturbance of cholera pits from the 19th century is non-existent as transmission is through contaminated water or food. An early 19th century incidence of asiatic cholera in Europe was recorded in Russia and other continental countries in the spring of 1831. The first occurrence in England was in the Autumn of 1831 when it reached Sunderland , by 1832 it was at Exeter, and it spread rapidly through the British Isles, reaching Kilmarnock in July 1832. Other less severe outbreaks were recorded in 1849 and 1853. In the United States of America, outbreaks of cholera took place in 1834, 1849, and 1861. At Barrmill in North Ayrshire the tradition is that the disease was passed on from a group of gypsies camped on Whin Hill that local boys had gone out to meet. Troops were regularly placed to prevent entry or exit during cholera outbreaks and normal burial in Beith was impossible and impractical, given the number of deaths. The burial site was fenced off and bordered by trees, kept in order by the Crawford Bros. from the factory until they died. It has been neglected since then. In 1834 cholera broke out in Beith and although 'clothes were burned, bedding fumigated, stairs and closes whitewashed, a nurse who was a veteran of the Dalry outbreak was engaged and a ban placed on entertainments at funerals.' There were 100 cases in September 1834, 205 people were eventually affected with 105 deaths. Some of the people were buried in the parish churchyard, but others were buried in a field, close to what became Spier's School, on the little common south-west of where the Geilsland Road meets the Powgree Burn. Robert Spier, the father of John Spier, was a member of the local Health Board. The burial at Cleeves Cove is said to that of a member of the family who lived at Cleeves Farm. Tradition has it that "A prediction was uttered many long ages ago, that Cleaves [ sic ] , on three successive occasions, would be the first place in the parish visited by the pestilence. The cholera of 1832 was called the fulfillment of the second visitation : accordingly, many of the older inhabitants talk of one still being in reserve." When attempting to create a burial pit in Little Bury Meadow near Exeter , the locals attacked the grave-digger when he arrived to break the ground. In Kilmarnock a patch of ground was purchased in Howard's Park "partly because the common-burying ground of the town was considered too small to meet the necessities of the case, and partly to prevent apprehended infection, as the graves in the new locality might remain in an undisturbed condition for a longer period." The construction of the proposed rail link to Glasgow Airport involved disturbance of the Paisley cholera pit; however, the project was cancelled. Nottingham - A cholera pit is located at Bellar Gate Rest Garden, at the corner of Bellar Gate and Barker Gate, commemorated with a plaque on the wall. The plaque reads: "This rest garden is on the site of an ancient burial ground associated with St. Mary's Church, and was granted to the parish for the sum of 10 shillings by Evelyn, Duke of Kingstone on 17th March 1742. In the 1830's it was used to accommodate the victims of a Cholera epidemic which struck Nottingham, and was finally closed in 1887." There is a cholera pit in Upton-upon-Severn , see York - a mass grave was located near the main railway station.Nottingham - A cholera pit is located at Bellar Gate Rest Garden, at the corner of Bellar Gate and Barker Gate, commemorated with a plaque on the wall. The plaque reads: "This rest garden is on the site of an ancient burial ground associated with St. Mary's Church, and was granted to the parish for the sum of 10 shillings by Evelyn, Duke of Kingstone on 17th March 1742. In the 1830's it was used to accommodate the victims of a Cholera epidemic which struck Nottingham, and was finally closed in 1887." There is a cholera pit in Upton-upon-Severn , see York - a mass grave was located near the main railway station.Nottingham - A cholera pit is located at Bellar Gate Rest Garden, at the corner of Bellar Gate and Barker Gate, commemorated with a plaque on the wall. The plaque reads: "This rest garden is on the site of an ancient burial ground associated with St. Mary's Church, and was granted to the parish for the sum of 10 shillings by Evelyn, Duke of Kingstone on 17th March 1742. In the 1830's it was used to accommodate the victims of a Cholera epidemic which struck Nottingham, and was finally closed in 1887."There is a cholera pit in Upton-upon-Severn , see York - a mass grave was located near the main railway station.

Wiki

Cholera

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

Gastroenteritis

Gastroenteritis , also known as infectious diarrhea or simply as gastro , is an inflammation of the gastrointestinal tract including the stomach and intestine . Symptoms may include diarrhea , vomiting , and abdominal pain . Fever , lack of energy, and dehydration may also occur. This typically lasts less than two weeks. Although it is not related to influenza , in the U.S. and U.K., it is sometimes called the " stomach flu ". Gastroenteritis is usually caused by viruses ; however, gut bacteria , parasites , and fungi can also cause gastroenteritis. In children, rotavirus is the most common cause of severe disease. In adults, norovirus and Campylobacter are common causes. Eating improperly prepared food, drinking contaminated water or close contact with a person who is infected can spread the disease . Treatment is generally the same with or without a definitive diagnosis, so testing to confirm is usually not needed. For young children in impoverished countries, prevention includes hand washing with soap, drinking clean water , breastfeeding babies instead of using formula , and proper disposal of human waste . The rotavirus vaccine is recommended as a prevention for children. Treatment involves getting enough fluids. For mild or moderate cases, this can typically be achieved by drinking oral rehydration solution (a combination of water, salts and sugar). In those who are breastfed, continued breastfeeding is recommended. For more severe cases, intravenous fluids may be needed. Fluids may also be given by a nasogastric tube . Zinc supplementation is recommended in children. Antibiotics are generally not needed. However, antibiotics are recommended for young children with a fever and bloody diarrhea. In 2015, there were two billion cases of gastroenteritis, resulting in 1.3 million deaths globally. Children and those in the developing world are affected the most. In 2011, there were about 1.7 billion cases, resulting in about 700,000 deaths of children under the age of five. In the developing world, children less than two years of age frequently get six or more infections a year. It is less common in adults, partly due to the development of immunity . Gastroenteritis usually involves both diarrhea and vomiting . Sometimes, only one or the other is present. This may be accompanied by abdominal cramps. Signs and symptoms usually begin 12–72 hours after contracting the infectious agent. If due to a virus, the condition usually resolves within one week. Some viral infections also involve fever , fatigue, headache and muscle pain . If the stool is bloody , the cause is less likely to be viral and more likely to be bacterial. Some bacterial infections cause severe abdominal pain and may persist for several weeks. Children infected with rotavirus usually make a full recovery within three to eight days. However, in poor countries treatment for severe infections is often out of reach and persistent diarrhea is common. Dehydration is a common complication of diarrhea . Severe dehydration in children may be recognized if the skin color and position returns slowly when pressed. This is called "prolonged capillary refill " and "poor skin turgor ". Abnormal breathing is another sign of severe dehydration. Repeat infections are typically seen in areas with poor sanitation, and malnutrition . Stunted growth and long-term cognitive delays can result. Reactive arthritis occurs in 1% of people following infections with Campylobacter species. Guillain–Barré syndrome occurs in 0.1%. Hemolytic uremic syndrome (HUS) may occur due to infection with Shiga toxin -producing Escherichia coli or Shigella species. HUS causes low platelet counts , poor kidney function , and low red blood cell count (due to their breakdown) . Children are more predisposed to getting HUS than adults. Some viral infections may produce benign infantile seizures . Viruses (particularly rotavirus (in children) and norovirus (in adults)) and the bacteria Escherichia coli and Campylobacter species are the primary causes of gastroenteritis. There are, however, many other infectious agents that can cause this syndrome including parasites and fungus . Non-infectious causes are seen on occasion, but they are less likely than a viral or bacterial cause. Risk of infection is higher in children due to their lack of immunity . Children are also at higher risk because they are less likely to practice good hygiene habits. Children living in areas without easy access to water and soap are especially vulnerable. Rotaviruses , noroviruses , adenoviruses , and astroviruses are known to cause viral gastroenteritis. Rotavirus is the most common cause of gastroenteritis in children, and produces similar rates in both the developed and developing world . Viruses cause about 70% of episodes of infectious diarrhea in the pediatric age group. Rotavirus is a less common cause in adults due to acquired immunity. Norovirus is the cause in about 18% of all cases. Generally speaking, viral gastroenteritis accounts for 21–40% of the cases of infectious diarrhea in developed countries. Norovirus is the leading cause of gastroenteritis among adults in America accounting for about 90% of viral gastroenteritis outbreaks. These localized epidemics typically occur when groups of people spend time proximate to each other, such as on cruise ships , in hospitals, or in restaurants. People may remain infectious even after their diarrhea has ended. Norovirus is the cause of about 10% of cases in children. In some countries, Campylobacter jejuni is the primary cause of bacterial gastroenteritis, with half of these cases associated with exposure to poultry . In children, bacteria are the cause in about 15% of cases, with the most common types being Escherichia coli , Salmonella , Shigella , and Campylobacter species. If food becomes contaminated with bacteria and remains at room temperature for a period of several hours, the bacteria multiply and increase the risk of infection in those who consume the food. Some foods commonly associated with illness include raw or undercooked meat, poultry, seafood, and eggs; raw sprouts; unpasteurized milk and soft cheeses; and fruit and vegetable juices. In the developing world, especially sub-Saharan Africa and Asia, cholera is a common cause of gastroenteritis. This infection is usually transmitted by contaminated water or food. Toxigenic Clostridium difficile is an important cause of diarrhea that occurs more often in the elderly. Infants can carry these bacteria without developing symptoms. It is a common cause of diarrhea in those who are hospitalized and is frequently associated with antibiotic use. Staphylococcus aureus infectious diarrhea may also occur in those who have used antibiotics. Acute " traveler's diarrhea " is usually a type of bacterial gastroenteritis, while the persistent form is usually parasitic. Acid-suppressing medication appears to increase the risk of significant infection after exposure to a number of organisms, including Clostridium difficile , Salmonella , and Campylobacter species. The risk is greater in those taking proton pump inhibitors than with H 2 antagonists . A number of parasites can cause gastroenteritis. Giardia lamblia is most common, but Entamoeba histolytica , Cryptosporidium spp., and other species have also been implicated. As a group, these agents comprise about 10% of cases in children. Giardia occurs more commonly in the developing world, but this type of illness can occur nearly everywhere. It occurs more commonly in persons who have traveled to areas with high prevalence, children who attend day care , men who have sex with men , and following disasters . Transmission may occur from drinking contaminated water or when people share personal objects. Water quality typically worsens during the rainy season and outbreaks are more common at this time. In areas with four seasons , infections are more common in the winter. Worldwide, bottle-feeding of babies with improperly sanitized bottles is a significant cause. Transmission rates are also related to poor hygiene, (especially among children), in crowded households, and in those with poor nutritional status. Adults who have developed immunities might still carry certain organisms without exhibiting symptoms. Thus, adults can become natural reservoirs of certain diseases. While some agents (such as Shigella ) only occur in primates , others (such as Giardia ) may occur in a wide variety of animals. There are a number of non-infectious causes of inflammation of the gastrointestinal tract. Some of the more common include medications (like NSAIDs ), certain foods such as lactose (in those who are intolerant), and gluten (in those with celiac disease ). Crohn's disease is also a non-infectious cause of (often severe) gastroenteritis. Disease secondary to toxins may also occur. Some food-related conditions associated with nausea, vomiting, and diarrhea include: ciguatera poisoning due to consumption of contaminated predatory fish, scombroid associated with the consumption of certain types of spoiled fish, tetrodotoxin poisoning from the consumption of puffer fish among others, and botulism typically due to improperly preserved food. In the United States, rates of emergency department use for noninfectious gastroenteritis dropped 30% from 2006 until 2011. Of the twenty most common conditions seen in the emergency department, rates of noninfectious gastroenteritis had the largest decrease in visits in that time period. Rotaviruses , noroviruses , adenoviruses , and astroviruses are known to cause viral gastroenteritis. Rotavirus is the most common cause of gastroenteritis in children, and produces similar rates in both the developed and developing world . Viruses cause about 70% of episodes of infectious diarrhea in the pediatric age group. Rotavirus is a less common cause in adults due to acquired immunity. Norovirus is the cause in about 18% of all cases. Generally speaking, viral gastroenteritis accounts for 21–40% of the cases of infectious diarrhea in developed countries. Norovirus is the leading cause of gastroenteritis among adults in America accounting for about 90% of viral gastroenteritis outbreaks. These localized epidemics typically occur when groups of people spend time proximate to each other, such as on cruise ships , in hospitals, or in restaurants. People may remain infectious even after their diarrhea has ended. Norovirus is the cause of about 10% of cases in children. In some countries, Campylobacter jejuni is the primary cause of bacterial gastroenteritis, with half of these cases associated with exposure to poultry . In children, bacteria are the cause in about 15% of cases, with the most common types being Escherichia coli , Salmonella , Shigella , and Campylobacter species. If food becomes contaminated with bacteria and remains at room temperature for a period of several hours, the bacteria multiply and increase the risk of infection in those who consume the food. Some foods commonly associated with illness include raw or undercooked meat, poultry, seafood, and eggs; raw sprouts; unpasteurized milk and soft cheeses; and fruit and vegetable juices. In the developing world, especially sub-Saharan Africa and Asia, cholera is a common cause of gastroenteritis. This infection is usually transmitted by contaminated water or food. Toxigenic Clostridium difficile is an important cause of diarrhea that occurs more often in the elderly. Infants can carry these bacteria without developing symptoms. It is a common cause of diarrhea in those who are hospitalized and is frequently associated with antibiotic use. Staphylococcus aureus infectious diarrhea may also occur in those who have used antibiotics. Acute " traveler's diarrhea " is usually a type of bacterial gastroenteritis, while the persistent form is usually parasitic. Acid-suppressing medication appears to increase the risk of significant infection after exposure to a number of organisms, including Clostridium difficile , Salmonella , and Campylobacter species. The risk is greater in those taking proton pump inhibitors than with H 2 antagonists . A number of parasites can cause gastroenteritis. Giardia lamblia is most common, but Entamoeba histolytica , Cryptosporidium spp., and other species have also been implicated. As a group, these agents comprise about 10% of cases in children. Giardia occurs more commonly in the developing world, but this type of illness can occur nearly everywhere. It occurs more commonly in persons who have traveled to areas with high prevalence, children who attend day care , men who have sex with men , and following disasters . Transmission may occur from drinking contaminated water or when people share personal objects. Water quality typically worsens during the rainy season and outbreaks are more common at this time. In areas with four seasons , infections are more common in the winter. Worldwide, bottle-feeding of babies with improperly sanitized bottles is a significant cause. Transmission rates are also related to poor hygiene, (especially among children), in crowded households, and in those with poor nutritional status. Adults who have developed immunities might still carry certain organisms without exhibiting symptoms. Thus, adults can become natural reservoirs of certain diseases. While some agents (such as Shigella ) only occur in primates , others (such as Giardia ) may occur in a wide variety of animals. There are a number of non-infectious causes of inflammation of the gastrointestinal tract. Some of the more common include medications (like NSAIDs ), certain foods such as lactose (in those who are intolerant), and gluten (in those with celiac disease ). Crohn's disease is also a non-infectious cause of (often severe) gastroenteritis. Disease secondary to toxins may also occur. Some food-related conditions associated with nausea, vomiting, and diarrhea include: ciguatera poisoning due to consumption of contaminated predatory fish, scombroid associated with the consumption of certain types of spoiled fish, tetrodotoxin poisoning from the consumption of puffer fish among others, and botulism typically due to improperly preserved food. In the United States, rates of emergency department use for noninfectious gastroenteritis dropped 30% from 2006 until 2011. Of the twenty most common conditions seen in the emergency department, rates of noninfectious gastroenteritis had the largest decrease in visits in that time period. Gastroenteritis is defined as vomiting or diarrhea due to inflammation of the small or large bowel , often due to infection. The changes in the small bowel are typically noninflammatory, while the ones in the large bowel are inflammatory. The number of pathogens required to cause an infection varies from as few as one (for Cryptosporidium ) to as many as 10 8 (for Vibrio cholerae ). Gastroenteritis is typically diagnosed clinically, based on a person's signs and symptoms. Determining the exact cause is usually not needed as it does not alter the management of the condition. However, stool cultures should be performed in those with blood in the stool, those who might have been exposed to food poisoning , and those who have recently traveled to the developing world. It may also be appropriate in children younger than 5, old people, and those with poor immune function. Diagnostic testing may also be done for surveillance. As hypoglycemia occurs in approximately 10% of infants and young children, measuring serum glucose in this population is recommended. Electrolytes and kidney function should also be checked when there is a concern about severe dehydration. A determination of whether or not the person has dehydration is an important part of the assessment, with dehydration typically divided into mild (3–5%), moderate (6–9%), and severe (≥10%) cases. In children, the most accurate signs of moderate or severe dehydration are a prolonged capillary refill , poor skin turgor , and abnormal breathing. Other useful findings (when used in combination) include sunken eyes, decreased activity, a lack of tears, and a dry mouth. A normal urinary output and oral fluid intake is reassuring. Laboratory testing is of little clinical benefit in determining the degree of dehydration. Thus the use of urine testing or ultrasounds is generally not needed. Other potential causes of signs and symptoms that mimic those seen in gastroenteritis that need to be ruled out include appendicitis , volvulus , inflammatory bowel disease , urinary tract infections , and diabetes mellitus . Pancreatic insufficiency , short bowel syndrome , Whipple's disease , coeliac disease , and laxative abuse should also be considered. The differential diagnosis can be complicated somewhat if the person exhibits only vomiting or diarrhea (rather than both). Appendicitis may present with vomiting, abdominal pain, and a small amount of diarrhea in up to 33% of cases. This is in contrast to the large amount of diarrhea that is typical of gastroenteritis. Infections of the lungs or urinary tract in children may also cause vomiting or diarrhea. Classical diabetic ketoacidosis (DKA) presents with abdominal pain, nausea, and vomiting, but without diarrhea. One study found that 17% of children with DKA were initially diagnosed as having gastroenteritis. A determination of whether or not the person has dehydration is an important part of the assessment, with dehydration typically divided into mild (3–5%), moderate (6–9%), and severe (≥10%) cases. In children, the most accurate signs of moderate or severe dehydration are a prolonged capillary refill , poor skin turgor , and abnormal breathing. Other useful findings (when used in combination) include sunken eyes, decreased activity, a lack of tears, and a dry mouth. A normal urinary output and oral fluid intake is reassuring. Laboratory testing is of little clinical benefit in determining the degree of dehydration. Thus the use of urine testing or ultrasounds is generally not needed. Other potential causes of signs and symptoms that mimic those seen in gastroenteritis that need to be ruled out include appendicitis , volvulus , inflammatory bowel disease , urinary tract infections , and diabetes mellitus . Pancreatic insufficiency , short bowel syndrome , Whipple's disease , coeliac disease , and laxative abuse should also be considered. The differential diagnosis can be complicated somewhat if the person exhibits only vomiting or diarrhea (rather than both). Appendicitis may present with vomiting, abdominal pain, and a small amount of diarrhea in up to 33% of cases. This is in contrast to the large amount of diarrhea that is typical of gastroenteritis. Infections of the lungs or urinary tract in children may also cause vomiting or diarrhea. Classical diabetic ketoacidosis (DKA) presents with abdominal pain, nausea, and vomiting, but without diarrhea. One study found that 17% of children with DKA were initially diagnosed as having gastroenteritis. A supply of easily accessible uncontaminated water and good sanitation practices are important for reducing rates of infection and clinically significant gastroenteritis. Personal hygiene measures (such as hand washing with soap) have been found to decrease rates of gastroenteritis in both the developing and developed world by as much as 30%. Alcohol-based gels may also be effective. Food or drink that is thought to be contaminated should be avoided. Breastfeeding is important, especially in places with poor hygiene, as is improvement of hygiene generally. Breast milk reduces both the frequency of infections and their duration. Due to both its effectiveness and safety, in 2009 the World Health Organization recommended that the rotavirus vaccine be offered to all children globally. Two commercial rotavirus vaccines exist and several more are in development. In Africa and Asia these vaccines reduced severe disease among infants and countries that have put in place national immunization programs have seen a decline in the rates and severity of disease. This vaccine may also prevent illness in non-vaccinated children by reducing the number of circulating infections. Since 2000, the implementation of a rotavirus vaccination program in the United States has substantially decreased the number of cases of diarrhea by as much as 80 percent. The first dose of vaccine should be given to infants between 6 and 15 weeks of age. The oral cholera vaccine has been found to be 50–60% effective over two years. There are a number of vaccines against gastroenteritis in development. For example, vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), which are two of the leading bacterial causes of gastroenteritis worldwide. A supply of easily accessible uncontaminated water and good sanitation practices are important for reducing rates of infection and clinically significant gastroenteritis. Personal hygiene measures (such as hand washing with soap) have been found to decrease rates of gastroenteritis in both the developing and developed world by as much as 30%. Alcohol-based gels may also be effective. Food or drink that is thought to be contaminated should be avoided. Breastfeeding is important, especially in places with poor hygiene, as is improvement of hygiene generally. Breast milk reduces both the frequency of infections and their duration. Due to both its effectiveness and safety, in 2009 the World Health Organization recommended that the rotavirus vaccine be offered to all children globally. Two commercial rotavirus vaccines exist and several more are in development. In Africa and Asia these vaccines reduced severe disease among infants and countries that have put in place national immunization programs have seen a decline in the rates and severity of disease. This vaccine may also prevent illness in non-vaccinated children by reducing the number of circulating infections. Since 2000, the implementation of a rotavirus vaccination program in the United States has substantially decreased the number of cases of diarrhea by as much as 80 percent. The first dose of vaccine should be given to infants between 6 and 15 weeks of age. The oral cholera vaccine has been found to be 50–60% effective over two years. There are a number of vaccines against gastroenteritis in development. For example, vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), which are two of the leading bacterial causes of gastroenteritis worldwide. Gastroenteritis is usually an acute and self-limiting disease that does not require medication. The preferred treatment in those with mild to moderate dehydration is oral rehydration therapy (ORT). For children at risk of dehydration from vomiting, taking a single dose of the anti vomiting medication metoclopramide or ondansetron , may be helpful, and butylscopolamine is useful in treating abdominal pain . The primary treatment of gastroenteritis in both children and adults is rehydration . This is preferably achieved by drinking rehydration solution, although intravenous delivery may be required if there is a decreased level of consciousness or if dehydration is severe. Drinking replacement therapy products made with complex carbohydrates (i.e. those made from wheat or rice) may be superior to those based on simple sugars. Drinks especially high in simple sugars, such as soft drinks and fruit juices, are not recommended in children under five years of age as they may increase diarrhea. Plain water may be used if more specific ORT preparations are unavailable or the person is not willing to drink them. A nasogastric tube can be used in young children to administer fluids if warranted. In those who require intravenous fluids, one to four hours' worth is often sufficient. It is recommended that breast-fed infants continue to be nursed in the usual fashion, and that formula-fed infants continue their formula immediately after rehydration with ORT. Lactose-free or lactose-reduced formulas usually are not necessary. Children should continue their usual diet during episodes of diarrhea with the exception that foods high in simple sugars should be avoided. The BRAT diet (bananas, rice, applesauce, toast and tea) is no longer recommended, as it contains insufficient nutrients and has no benefit over normal feeding. A Cochrane Review from 2020 concludes that probiotics make little or no difference to people who have diarrhea lasting 2 days or longer and that there is no proof that they reduce its duration. They may be useful in preventing and treating antibiotic associated diarrhea . Fermented milk products (such as yogurt ) are similarly beneficial. Zinc supplementation appears to be effective in both treating and preventing diarrhea among children in the developing world. Antiemetic medications may be helpful for treating vomiting in children. Ondansetron has some utility, with a single dose being associated with less need for intravenous fluids, fewer hospitalizations, and decreased vomiting. Metoclopramide might also be helpful. However, the use of ondansetron might possibly be linked to an increased rate of return to hospital in children. The intravenous preparation of ondansetron may be given orally if clinical judgment warrants. Dimenhydrinate , while reducing vomiting, does not appear to have a significant clinical benefit. Antibiotics are not usually used for gastroenteritis, although they are sometimes recommended if symptoms are particularly severe or if a susceptible bacterial cause is isolated or suspected. If antibiotics are to be employed, a macrolide (such as azithromycin ) is preferred over a fluoroquinolone due to higher rates of resistance to the latter. Pseudomembranous colitis , usually caused by antibiotic use, is managed by discontinuing the causative agent and treating it with either metronidazole or vancomycin . Bacteria and protozoans that are amenable to treatment include Shigella Salmonella typhi , and Giardia species. In those with Giardia species or Entamoeba histolytica , tinidazole treatment is recommended and superior to metronidazole. The World Health Organization (WHO) recommends the use of antibiotics in young children who have both bloody diarrhea and fever. Antimotility medication has a theoretical risk of causing complications, and although clinical experience has shown this to be unlikely, these drugs are discouraged in people with bloody diarrhea or diarrhea that is complicated by fever. Loperamide , an opioid analogue, is commonly used for the symptomatic treatment of diarrhea. Loperamide is not recommended in children, however, as it may cross the immature blood–brain barrier and cause toxicity. Bismuth subsalicylate , an insoluble complex of trivalent bismuth and salicylate, can be used in mild to moderate cases, but salicylate toxicity is theoretically possible. The primary treatment of gastroenteritis in both children and adults is rehydration . This is preferably achieved by drinking rehydration solution, although intravenous delivery may be required if there is a decreased level of consciousness or if dehydration is severe. Drinking replacement therapy products made with complex carbohydrates (i.e. those made from wheat or rice) may be superior to those based on simple sugars. Drinks especially high in simple sugars, such as soft drinks and fruit juices, are not recommended in children under five years of age as they may increase diarrhea. Plain water may be used if more specific ORT preparations are unavailable or the person is not willing to drink them. A nasogastric tube can be used in young children to administer fluids if warranted. In those who require intravenous fluids, one to four hours' worth is often sufficient. It is recommended that breast-fed infants continue to be nursed in the usual fashion, and that formula-fed infants continue their formula immediately after rehydration with ORT. Lactose-free or lactose-reduced formulas usually are not necessary. Children should continue their usual diet during episodes of diarrhea with the exception that foods high in simple sugars should be avoided. The BRAT diet (bananas, rice, applesauce, toast and tea) is no longer recommended, as it contains insufficient nutrients and has no benefit over normal feeding. A Cochrane Review from 2020 concludes that probiotics make little or no difference to people who have diarrhea lasting 2 days or longer and that there is no proof that they reduce its duration. They may be useful in preventing and treating antibiotic associated diarrhea . Fermented milk products (such as yogurt ) are similarly beneficial. Zinc supplementation appears to be effective in both treating and preventing diarrhea among children in the developing world. Antiemetic medications may be helpful for treating vomiting in children. Ondansetron has some utility, with a single dose being associated with less need for intravenous fluids, fewer hospitalizations, and decreased vomiting. Metoclopramide might also be helpful. However, the use of ondansetron might possibly be linked to an increased rate of return to hospital in children. The intravenous preparation of ondansetron may be given orally if clinical judgment warrants. Dimenhydrinate , while reducing vomiting, does not appear to have a significant clinical benefit. Antibiotics are not usually used for gastroenteritis, although they are sometimes recommended if symptoms are particularly severe or if a susceptible bacterial cause is isolated or suspected. If antibiotics are to be employed, a macrolide (such as azithromycin ) is preferred over a fluoroquinolone due to higher rates of resistance to the latter. Pseudomembranous colitis , usually caused by antibiotic use, is managed by discontinuing the causative agent and treating it with either metronidazole or vancomycin . Bacteria and protozoans that are amenable to treatment include Shigella Salmonella typhi , and Giardia species. In those with Giardia species or Entamoeba histolytica , tinidazole treatment is recommended and superior to metronidazole. The World Health Organization (WHO) recommends the use of antibiotics in young children who have both bloody diarrhea and fever. Antimotility medication has a theoretical risk of causing complications, and although clinical experience has shown this to be unlikely, these drugs are discouraged in people with bloody diarrhea or diarrhea that is complicated by fever. Loperamide , an opioid analogue, is commonly used for the symptomatic treatment of diarrhea. Loperamide is not recommended in children, however, as it may cross the immature blood–brain barrier and cause toxicity. Bismuth subsalicylate , an insoluble complex of trivalent bismuth and salicylate, can be used in mild to moderate cases, but salicylate toxicity is theoretically possible. It is estimated that there were two billion cases of gastroenteritis that resulted in 1.3 million deaths globally in 2015. Children and those in the developing world are most commonly affected. As of 2011, in those younger than five, there were about 1.7 billion cases resulting in 0.7 million deaths, with most of these occurring in the world's poorest nations. More than 450,000 of these fatalities are due to rotavirus in children under five years of age. Cholera causes about three to five million cases of disease and kills approximately 100,000 people yearly. In the developing world, children less than two years of age frequently get six or more infections a year that result in significant gastroenteritis. It is less common in adults, partly due to the development of acquired immunity . In 1980, gastroenteritis from all causes caused 4.6 million deaths in children, with the majority occurring in the developing world. Death rates were reduced significantly (to approximately 1.5 million deaths annually) by 2000, largely due to the introduction and widespread use of oral rehydration therapy . In the US, infections causing gastroenteritis are the second most common infection (after the common cold ), and they result in between 200 and 375 million cases of acute diarrhea and approximately ten thousand deaths annually, with 150 to 300 of these deaths in children less than five years of age. Gastroenteritis is associated with many colloquial names, including " Montezuma's revenge ", "Delhi belly", "la turista", and "back door sprint", among others. It has played a role in many military campaigns and is believed to be the origin of the term "no guts no glory". Gastroenteritis is the main reason for 3.7 million visits to physicians a year in the United States and 3 million visits in France. In the United States gastroenteritis as a whole is believed to result in costs of US$23 billion per year, with rotavirus alone resulting in estimated costs of US$1 billion a year. The first usage of "gastroenteritis" was in 1825. Before this time it was commonly known as typhoid fever or "cholera morbus", among others, or less specifically as "griping of the guts", "surfeit", "flux", "colic", "bowel complaint", or any one of a number of other archaic names for acute diarrhea. Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically cholera . Many of the same agents cause gastroenteritis in cats and dogs as in humans. The most common organisms are Campylobacter , Clostridium difficile , Clostridium perfringens , and Salmonella . A large number of toxic plants may also cause symptoms. Some agents are more specific to a certain species. Transmissible gastroenteritis coronavirus (TGEV) occurs in pigs resulting in vomiting, diarrhea, and dehydration. It is believed to be introduced to pigs by wild birds and there is no specific treatment available. It is not transmissible to humans.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/Love_in_the_Time_of_Cholera_(film)/html

Love in the Time of Cholera (film)

November 16, 2007 ( 2007-11-16 ) Love in the Time of Cholera is a 2007 American romantic drama film directed by Mike Newell . Based on the 1985 novel of the same name by the Colombian Nobel Prize -winning author Gabriel García Márquez , it tells the story of a love triangle between Fermina Daza (played by Giovanna Mezzogiorno ) and her two suitors, Florentino Ariza ( Javier Bardem ) and Doctor Juvenal Urbino ( Benjamin Bratt ) which spans 50 years, from 1880 to 1930. It is the first filming of a García Márquez novel by a Hollywood studio, rather than by Latin American or Italian directors. It is also the first English-language work of Academy Award -nominated Brazilian actress Fernanda Montenegro , who portrays Tránsito Ariza. Shakira wrote two original songs " Hay Amores " and " Despedida " for the film.In late 19th-century Cartagena , a river port in Colombia, Florentino Ariza falls in love at first sight with Fermina Daza. They secretly correspond, and she eventually agrees to marry him, but her father discovers their relationship and sends her to stay with distant relatives (mainly her grandmother and niece). When she returns some years later, Fermina agrees to marry Dr. Juvenal Urbino, her father's choice. Their 50-year marriage is outwardly loving but inwardly marred by darker emotions. Fermina's marriage devastates Florentino, who vows to remain a virgin, but his self-denial is thwarted by a tryst. To help Florentino get over Fermina, his mother throws a willing widow into his bed, and Florentino discovers that sex is a very good pain reliever, one he uses to replace the opium that he had habitually smoked. Florentino begins to record and describe each of his sexual encounters, beginning with the widow, and eventually compiles over 600 entries. Now a lowly clerk, Florentino plods resolutely over many years to approach the wealth and social standing of Dr. Urbino. When the now-elderly doctor dies suddenly, Florentino immediately and impertinently resumes courting Fermina.Much of the film takes place in the historic, walled city of Cartagena in Colombia . Some screen shots showed the Magdalena River and the Sierra Nevada de Santa Marta mountain range. The London-based animation studio VooDooDog created the title and end sequences, which draw inspiration from the colors and atmosphere of South America. We put a lot of effort into the line test stage, studying time-lapse flowers footage and getting the twisting feeling of the tendrils and flowers opening before committing to the hand painting stage. I am sure no one other than fussy designers notice, but we think it was worth the effort rather than just making a straight computerised sequence.Much of the film takes place in the historic, walled city of Cartagena in Colombia . Some screen shots showed the Magdalena River and the Sierra Nevada de Santa Marta mountain range. The London-based animation studio VooDooDog created the title and end sequences, which draw inspiration from the colors and atmosphere of South America. We put a lot of effort into the line test stage, studying time-lapse flowers footage and getting the twisting feeling of the tendrils and flowers opening before committing to the hand painting stage. I am sure no one other than fussy designers notice, but we think it was worth the effort rather than just making a straight computerised sequence.According to an interview by Colombian magazine Revista Semana , Scott Steindorff , producer of the film, showed an unreleased final edition of the film to Gabriel García Márquez in Mexico who, at the end of the film, is said to have exclaimed "Bravo!" with a smile on his face. On Rotten Tomatoes , the film has an approval rating of 25% based on reviews from 110 critics, with an average rating of 4.7/10. The website's critical consensus reads, "Though beautifully filmed, the makers of Love in the Time of Cholera fail to transfer the novel's magic to the screen." On Metacritic , the film had an average score of 43 out of 100, based on 29 reviews, indicating "mixed or average reviews". Time rated it "D" and described it as "a serious contender [for] the worst movie ever made from a great novel ... Skip the film; reread the book." Lisa Schwarzbaum of Entertainment Weekly , gave it a "D" rating and called it a "turgid and lifeless movie adaptation", opining that "those who have read Gabriel García Márquez's glowing and sexy 1988 novel about one man's grand love for a woman who marries another are bound to be peevishly disappointed ... those who haven't read the book will now never understand the ardor of those who have — at least not based on all the hammy traipsing and coupling and scene-hopping thrown together here." In the Los Angeles Times , Carina Chocano stated, "the novel has made it to the screen in the form of a plodding, tone-deaf, overripe, overheated Oscar baiting telenovela ... Doubtless it's an enormously daunting task to adapt a book at once so sweeping and internal, so swooningly romantic and philosophical, but it takes a lighter touch and a more expansive view than Newell and Harwood seem to bring." Despedida, written for the film by Shakira and Antonio Pinto , was nominated for a Golden Globe for Best Song. In its opening weekend in the United States and Canada, the film ranked #10 at the box office, grossing $1.9 million in 852 theaters. According to an interview by Colombian magazine Revista Semana , Scott Steindorff , producer of the film, showed an unreleased final edition of the film to Gabriel García Márquez in Mexico who, at the end of the film, is said to have exclaimed "Bravo!" with a smile on his face. On Rotten Tomatoes , the film has an approval rating of 25% based on reviews from 110 critics, with an average rating of 4.7/10. The website's critical consensus reads, "Though beautifully filmed, the makers of Love in the Time of Cholera fail to transfer the novel's magic to the screen." On Metacritic , the film had an average score of 43 out of 100, based on 29 reviews, indicating "mixed or average reviews". Time rated it "D" and described it as "a serious contender [for] the worst movie ever made from a great novel ... Skip the film; reread the book." Lisa Schwarzbaum of Entertainment Weekly , gave it a "D" rating and called it a "turgid and lifeless movie adaptation", opining that "those who have read Gabriel García Márquez's glowing and sexy 1988 novel about one man's grand love for a woman who marries another are bound to be peevishly disappointed ... those who haven't read the book will now never understand the ardor of those who have — at least not based on all the hammy traipsing and coupling and scene-hopping thrown together here." In the Los Angeles Times , Carina Chocano stated, "the novel has made it to the screen in the form of a plodding, tone-deaf, overripe, overheated Oscar baiting telenovela ... Doubtless it's an enormously daunting task to adapt a book at once so sweeping and internal, so swooningly romantic and philosophical, but it takes a lighter touch and a more expansive view than Newell and Harwood seem to bring." Despedida, written for the film by Shakira and Antonio Pinto , was nominated for a Golden Globe for Best Song. In its opening weekend in the United States and Canada, the film ranked #10 at the box office, grossing $1.9 million in 852 theaters.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/Cholera_(food)/html

Cholera (food)

A cholera is a pastry filled with potatoes , vegetables , fruits and cheese , originated from the Valais region of Switzerland. Originally, the local ingredients for such a dish were apples , pears , potatoes , onions , leeks , raclette cheese (usually Gomser) and bacon . The dish is mostly known in the region of Valais within Switzerland.The origin of the unusual name for the dish remains unclear. A folk etymological explanation purports that during an epidemic of the disease cholera in 1836, people in the region improvised a dish involving pastry and whatever food they had at hand, as normal trade was disrupted. After the epidemic subsided, chefs returned to the concept of putting regional ingredients in a savoury tart, and the "cholera" dish has lasted since. However, various other linguistic theories try to link the origin of the name to Chola or Cholu (Valais German for coal ) as the pastry would be baked on coals. Alternatively, Cholära is also the Valais German term for a specific room within a bakery where coal would be gathered.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/Diseases_and_epidemics_of_the_19th_century/html

Diseases and epidemics of the 19th century

Diseases and epidemics of the 19th century included long-standing epidemic threats such as smallpox , typhus , yellow fever , and scarlet fever . In addition, cholera emerged as an epidemic threat and spread worldwide in six pandemics in the nineteenth century.Epidemics of the 19th century were faced without the medical advances that made 20th-century epidemics much rarer and less lethal. Micro-organisms (viruses and bacteria) had been discovered in the 18th century, but it was not until the late 19th century that the experiments of Lazzaro Spallanzani and Louis Pasteur disproved spontaneous generation conclusively, allowing germ theory and Robert Koch 's discovery of micro-organisms as the cause of disease transmission . Thus throughout the majority of the 19th century, there was only the most basic, common-sense understanding of the causes, amelioration, and treatment of epidemic disease. [ citation needed ] The 19th century did, however, mark a transformation period in medicine. This included the first uses of chloroform and nitrous dioxides as anesthesia, important discoveries in regards of pathology and the perfection of the autopsy , and advances in our understanding of the human body. Medical institutions were also transitioning to new hospital styles to try to prevent the spread of disease and stop over crowding with the mixing of the poor and the sick which had been a common practice. With the increasing rise in urban population, disease and epidemic crisis became much more prevalent and was seen as a consequence of urban living. Problems arose as both governments and the medical professionals at the time tried to get a handle on the spread of disease. They had yet to figure out what actually causes disease. So as those in authority scrambled to make leaps and bounds in science and track down what may be the cause of these epidemics, entire communities would be lost to the grips of terrible ailments. During these many outbreaks, members of the medical profession rapidly began trying different cures to treat their patients. During the cholera epidemic of 1832 , a doctor in London, Thomas Latta , discovered that he could greatly increase the survival rate of his patients by injecting saline solutions into their arms. However, due to the wide range of medicines being touted as cures and treatments, his technique failed to gain widespread adoption. Many other medical discoveries made in the 19th century failed to gain traction for similar reasons. With the increasing circulation of mass media and little content review in medical journals , almost anyone with or without proper education could publish a potential cure for disease. Actual practicing medical professionals also had to compete with the ever expanding pharmacy companies that were all too ready to provide new elixirs and promising treatments for the epidemics of the time. Emerging from the medical chaos were legitimate and life changing treatments. The late 19th century was the beginning of widespread use of vaccines . The cholera bacterium was isolated in 1854 by Italian anatomist Filippo Pacini , and a vaccine, the first to immunize humans against a bacterial disease, was developed by Spanish physician Jaume Ferran i Clua in 1885, and by Russian–Jewish bacteriologist Waldemar Haffkine in July 1892. Antibiotic drugs did not appear until the middle of the 20th century. Sulfonamides did not appear until 1935 , and penicillin , discovered in 1928, was not available as a treatment until 1950. [ citation needed ] A big response and potential cure to these epidemics were better sanitation in the cities. Sanitation prior to this was very poor and sometimes attempts to get better sanitation often exacerbated the diseases, especially during the cholera epidemics because their understanding of diseases relied on the miasma (bad air) theory . During the first cholera epidemic, Edwin Chadwick made an inquiry into sanitation and used quantitative data to link poor living conditions and disease and low life expectancy. As a result, the Board of Health in London took measure to improve drainage and ventilation around the city. Unfortunately, the measures helped clean the city but it further contaminated the River Thames (the primary drinking water for the city) and the epidemic got worse. During the second cholera pandemic of 1816–1837, the scientific community varied in its beliefs about its causes. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious and quarantined their citizens. The United States believed that cholera was brought by recent immigrants, specifically the Irish. Lastly, some British thought the disease might arise from divine intervention. During the third pandemic , Tunisia, which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. The prevalence of the disease in the South in areas of black populations convinced United States scientists that cholera was associated with African Americans. Current researchers note they lived near the waterways by which travelers and ships carried the disease and their populations were underserved with sanitation infrastructure and health care. The Soho outbreak in London in 1854 ended after the physician John Snow identified a neighborhood Broad Street pump as contaminated and convinced officials to remove its handle. Snow believed that germ-contaminated water was the source of cholera , rather than particles in the air (referred to as "miasmata"). His study proved contaminated water was the main agent spreading cholera, although he did not identify the contaminant. Though Filippo Pacini had isolated Vibrio cholerae as the causative agent for cholera that year, it would be many years before miasma theory would fall out of favor. [ citation needed ] In London, in June 1866 ), a localized epidemic in the East End claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems. William Farr , using the work of John Snow, et al. , as to contaminated drinking water being the likely source of the disease, relatively quickly identified the East London Water Company as the source of the contaminated water. Quick action prevented further deaths. During the fifth cholera pandemic , Robert Koch isolated Vibrio cholerae and proposed postulates to explain how bacteria caused disease. His work helped to establish the germ theory of disease . Prior to this time, many physicians believed that microorganisms were spontaneously generated, and disease was caused by direct exposure to filth and decay. Koch helped establish that the disease was more specifically contagious and was transmittable through the contaminated water supply. The fifth was the last serious European cholera outbreak, as cities improved their sanitation and water systems. [ citation needed ]Epidemics of the 19th century were faced without the medical advances that made 20th-century epidemics much rarer and less lethal. Micro-organisms (viruses and bacteria) had been discovered in the 18th century, but it was not until the late 19th century that the experiments of Lazzaro Spallanzani and Louis Pasteur disproved spontaneous generation conclusively, allowing germ theory and Robert Koch 's discovery of micro-organisms as the cause of disease transmission . Thus throughout the majority of the 19th century, there was only the most basic, common-sense understanding of the causes, amelioration, and treatment of epidemic disease. [ citation needed ] The 19th century did, however, mark a transformation period in medicine. This included the first uses of chloroform and nitrous dioxides as anesthesia, important discoveries in regards of pathology and the perfection of the autopsy , and advances in our understanding of the human body. Medical institutions were also transitioning to new hospital styles to try to prevent the spread of disease and stop over crowding with the mixing of the poor and the sick which had been a common practice. With the increasing rise in urban population, disease and epidemic crisis became much more prevalent and was seen as a consequence of urban living. Problems arose as both governments and the medical professionals at the time tried to get a handle on the spread of disease. They had yet to figure out what actually causes disease. So as those in authority scrambled to make leaps and bounds in science and track down what may be the cause of these epidemics, entire communities would be lost to the grips of terrible ailments. During these many outbreaks, members of the medical profession rapidly began trying different cures to treat their patients. During the cholera epidemic of 1832 , a doctor in London, Thomas Latta , discovered that he could greatly increase the survival rate of his patients by injecting saline solutions into their arms. However, due to the wide range of medicines being touted as cures and treatments, his technique failed to gain widespread adoption. Many other medical discoveries made in the 19th century failed to gain traction for similar reasons. With the increasing circulation of mass media and little content review in medical journals , almost anyone with or without proper education could publish a potential cure for disease. Actual practicing medical professionals also had to compete with the ever expanding pharmacy companies that were all too ready to provide new elixirs and promising treatments for the epidemics of the time. Emerging from the medical chaos were legitimate and life changing treatments. The late 19th century was the beginning of widespread use of vaccines . The cholera bacterium was isolated in 1854 by Italian anatomist Filippo Pacini , and a vaccine, the first to immunize humans against a bacterial disease, was developed by Spanish physician Jaume Ferran i Clua in 1885, and by Russian–Jewish bacteriologist Waldemar Haffkine in July 1892. Antibiotic drugs did not appear until the middle of the 20th century. Sulfonamides did not appear until 1935 , and penicillin , discovered in 1928, was not available as a treatment until 1950. [ citation needed ] A big response and potential cure to these epidemics were better sanitation in the cities. Sanitation prior to this was very poor and sometimes attempts to get better sanitation often exacerbated the diseases, especially during the cholera epidemics because their understanding of diseases relied on the miasma (bad air) theory . During the first cholera epidemic, Edwin Chadwick made an inquiry into sanitation and used quantitative data to link poor living conditions and disease and low life expectancy. As a result, the Board of Health in London took measure to improve drainage and ventilation around the city. Unfortunately, the measures helped clean the city but it further contaminated the River Thames (the primary drinking water for the city) and the epidemic got worse. During the second cholera pandemic of 1816–1837, the scientific community varied in its beliefs about its causes. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious and quarantined their citizens. The United States believed that cholera was brought by recent immigrants, specifically the Irish. Lastly, some British thought the disease might arise from divine intervention. During the third pandemic , Tunisia, which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. The prevalence of the disease in the South in areas of black populations convinced United States scientists that cholera was associated with African Americans. Current researchers note they lived near the waterways by which travelers and ships carried the disease and their populations were underserved with sanitation infrastructure and health care. The Soho outbreak in London in 1854 ended after the physician John Snow identified a neighborhood Broad Street pump as contaminated and convinced officials to remove its handle. Snow believed that germ-contaminated water was the source of cholera , rather than particles in the air (referred to as "miasmata"). His study proved contaminated water was the main agent spreading cholera, although he did not identify the contaminant. Though Filippo Pacini had isolated Vibrio cholerae as the causative agent for cholera that year, it would be many years before miasma theory would fall out of favor. [ citation needed ] In London, in June 1866 ), a localized epidemic in the East End claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems. William Farr , using the work of John Snow, et al. , as to contaminated drinking water being the likely source of the disease, relatively quickly identified the East London Water Company as the source of the contaminated water. Quick action prevented further deaths. During the fifth cholera pandemic , Robert Koch isolated Vibrio cholerae and proposed postulates to explain how bacteria caused disease. His work helped to establish the germ theory of disease . Prior to this time, many physicians believed that microorganisms were spontaneously generated, and disease was caused by direct exposure to filth and decay. Koch helped establish that the disease was more specifically contagious and was transmittable through the contaminated water supply. The fifth was the last serious European cholera outbreak, as cities improved their sanitation and water systems. [ citation needed ]Cholera is an infection of the small intestine caused by the bacterium Vibrio cholerae . Cholera is transmitted primarily by drinking water or eating food that has been contaminated by the cholera bacterium. The bacteria multiply in the small intestine; the feces (waste product) of an infected person, including one with no apparent symptoms, can pass on the disease if it contacts the water supply by any means. History does not recount any incidents of cholera until the 19th century . Cholera came in seven waves, the last two of which occurred in the 20th century. [ citation needed ] The first cholera pandemic started in 1816, spread across India by 1820, and extended to Southeast Asia and Central Europe, lasting until 1826. A second cholera pandemic began in 1829, reached Russia, causing the Cholera riots . It spread to Hungary , Germany and Egypt in 1831, and London, Paris, Quebec , Ontario and New York City the following year. Cholera reached the Pacific coast of North America by 1834, reaching into the center of the country by steamboat and other river traffic. The third cholera pandemic began in 1846 and lasted until 1860. It hit Russia hardest, with over one million deaths. In 1846, cholera struck Mecca , killing over 15,000. A two-year outbreak began in England and Wales in 1848, and claimed 52,000 lives. In 1849, outbreak occurred again in Paris, and in London, killing 14,137, over twice as many as the 1832 outbreak. Cholera hit Ireland in 1849 and killed many of the Irish Famine survivors, already weakened by starvation and fever. In 1849, cholera claimed 5,308 lives in the major port city of Liverpool , England, an embarkation point for immigrants to North America, and 1,834 in Hull , England. Cholera spread throughout the Mississippi River system. Thousands died in New York City, a major destination for Irish immigrants. Cholera killed 200,000 people in Mexico. That year, cholera was transmitted along the California , Mormon and Oregon Trails , killing people that are believed to have died on their way to the California Gold Rush , Utah and Oregon in the cholera years of 1849–1855. In 1851, a ship coming from Cuba carried the disease to Gran Canaria , killing up to 6,000 people. The pandemic spread east to Indonesia by 1852, and China and Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal contributed to transmission of the disease by travelers and troops to Iran , Iraq , Arabia and Russia. Japan suffered at least seven major outbreaks of cholera between 1858 and 1902. The Ansei outbreak of 1858–60, for example, is believed to have killed between 100,000 and 200,000 people in Tokyo alone. An outbreak of cholera in Chicago in 1854 took the lives of 5.5% of the population (about 3,500 people). In 1853–4, London's epidemic claimed 10,738 lives. Throughout Spain , cholera caused more than 236,000 deaths in 1854–55. In 1854, it entered Venezuela; Brazil also suffered in 1855. The fourth cholera pandemic (1863–1875) spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims died from the disease. Cholera ravaged northern Africa in 1865 and southeastward to Zanzibar , killing 70,000 in 1869–70. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have killed 165,000 people in the Austrian Empire . In 1867, 113,000 died from cholera in Italy. and 80,000 in Algeria . Outbreaks in North America in 1866–1873 killed some 50,000 Americans. In 1866, localized epidemics occurred in the East End of London, in southern Wales , and Amsterdam . In the 1870s, cholera spread in the U.S. as an epidemic from New Orleans along the Mississippi River and to ports on its tributaries. [ citation needed ] In the fifth cholera pandemic (1881–1896), according to Dr A. J. Wall, the 1883–1887 part of the epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas. Cholera claimed 267,890 lives in Russia (1892); 120,000 in Spain ; 90,000 in Japan and over 60,000 in Persia . In Egypt , cholera claimed more than 58,000 lives. The 1892 outbreak in Hamburg killed 8,600 people. [ citation needed ]Smallpox is caused by either of the two viruses, Variola major and Variola minor. Smallpox vaccine was available in Europe, the United States, and the Spanish Colonies during the last part of the century. The Latin names of this disease are Variola Vera. The words come from various (spotted) or varus (pimple). In England, this disease was first known as the "pox" or the "red plague". Smallpox settles itself in small blood vessels of the skin and in the mouth and throat. The symptoms of smallpox are rash on the skin and blisters filled with raised liquid. [ citation needed ] The disease killed an estimated 400,000 Europeans annually during the 19th century and one-third of all the blindness of that time was caused by smallpox. 20 to 60% of all the people that were infected died and 80% of all the children with the infection also died. It caused also many deaths in the 20th century, over 300–500 million. Wolfgang Amadeus Mozart also had smallpox when he was only 11 years old. He survived the smallpox outbreak in Austria. [ citation needed ]Epidemic typhus is caused by the bacteria Rickettsia Prowazekii; it comes from lice . Murine typhus is caused by the Rickettsia Typhi bacteria, from the fleas on rats. Scrub typhus is caused by the Orientia Tsutsugamushi bacteria, from the harvest mites on humans and rodents. Queensland tick typhus is caused by the Rickettsia Australis bacteria, from ticks . [ citation needed ] During Napoleon 's retreat from Moscow in 1812, more French soldiers died of typhus than were killed by the Russians. A major epidemic occurred in Ireland between 1816 and 1819, during the Year Without a Summer ; an estimated 100,000 Irish perished. Typhus appeared again in the late 1830s, and between 1846 and 1849 during the Great Irish Famine . Spreading to England, and called "Irish fever", it was noted for its virulence. It killed people of all social classes, as lice were endemic and inescapable, but it hit particularly hard in the lower or "unwashed" social strata. In Canada alone, the typhus epidemic of 1847 killed more than 20,000 people from 1847 to 1848, mainly Irish immigrants in fever sheds and other forms of quarantine, who had contracted the disease aboard coffin ships . In the United States, epidemics occurred in Baltimore , Memphis and Washington DC between 1865 and 1873, and during the US Civil War . [ citation needed ]This disease is transmitted by the bite of female mosquito; the higher prevalence of transmission by Aedes aegypti has led to it being known as the Yellow Fever Mosquito. The transmission of yellow fever is entirely a matter of available habitat for vector mosquito and prevention such as mosquito netting. They mostly infect other primates, but humans can be infected. The symptoms of the fever are: Headaches, back and muscle pain, chills and vomiting, bleeding in the eyes and mouth, and vomit containing blood. [ citation needed ] Yellow fever accounted for the largest number of the 19th-century's individual epidemic outbreaks, and most of the recorded serious outbreaks of yellow fever occurred in the 19th century. It is most prevalent in tropical-like climates, but the United States was not exempted from the fever. New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853. At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Santo Domingo in 1803 and Memphis in 1878 . Major outbreaks occurred repeatedly in Gibraltar ; outbreaks in 1804, 1814, and again in 1828. Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans . The third plague pandemic was a major bubonic plague pandemic that began in Yunnan , China in 1855. This episode of bubonic plague spread to all inhabited continents in the 1890s and first years of the 1900s, and ultimately led to more than 12,000,000 deaths in India and China, with about 10,000,000 killed in India alone. A natural reservoir of plague is located in western Yunnan and is an ongoing health risk today. The third pandemic of plague originated in this area after a rapid influx of Han Chinese to exploit the demand for minerals, primarily copper, in the latter half of the 19th century. By 1850, the population had exploded to over 7,000,000 people. Increasing transportation throughout the region brought people in contact with plague-infected fleas , the primary vector between the yellow-breasted rat ( Rattus flavipectus ) and humans. The spread of European empires and the development of new forms of transport such as the steam engine made it easier for both humans and rats to spread the disease along existing trade routes. [ citation needed ]Haemolytic streptococcus, which was identified in the 1880s, causes scarlet fever , which is a bacterial disease. Scarlet fever spreads through respiratory droplets and children between the ages of 5 and 15 years were most affected by scarlet fever. Scarlet fever had several epidemic phases, and around 1825 to 1885 outbreaks began to recur cyclically and often highly fatal. In the mid-19th century, the mortality caused by scarlet fever rose in England and Wales . The major outbreak in England and Wales took place during 1825–1885 with high mortality marking this as remarkable. There were several other notable outbreaks across Europe, South America, and the United States in the 19th century. In the UK, scarlet fever was considered benign for two centuries, but fatal epidemics were seen in the 1700s. Scarlet fever broke out in England in the 19th century and was responsible for an enormous number of deaths in the 60-year period from 1825 to 1885; decades that followed had lower levels of annual mortality from scarlet fever. In NW England there was heavy mortality in Liverpool . Babies born in Liverpool with a birthday in 1861 were only expected to live 26 years, and in larger cities, life expectancy was less than 35 years. Over time, the life expectancy changed as well as the number of fatalities from scarlet fever. There was a reduction in child mortality from scarlet fever when you compare the decades, 1851–60 and 1891–1900. The decline of mortality seen for scarlet fever was noticed after the identification of streptococcus , but the decline was not associated with a treatment. A treatment would not be available until the introduction of sulphonamides in the 1930s, and the decline in mortality was due to the quality of air, food, and water improving. Outbreaks of scarlet fever also took place in Dublin in 1896 with 1,354 cases and 149 deaths, Norway from 1862 to 1884, Scotland in 1861, and in the rest of United Kingdom. The United Kingdom saw cases in Canterbury from 1839 to 1865 with 305 deaths, Bristol in 1870 with 106 deaths and in 1875, and Manchester in 1886 with six cases. Chile reported scarlet fever the first time in 1827 and highest rates were seen during winter months. The disease spread from Valparaiso to Santiago from 1831 to 1832 and claimed 7,000 lives. There were multiple outbreaks in different locations of Chile, including Copaipo in 1875 and Caldera in 1876. Similarly to Europe, America considered scarlet fever to be benign for two centuries. In the early 19th century the scarlet fever impact drastically changed and lethal epidemics started to arise in the United States. The United States had a notable outbreak of scarlet fever in Minnesota in 1847 and Augusta, Georgia had a lethal epidemic in 1832–1833. Scarlet fever had low mortality rates in New York for many years before 1828, but remained high for long after. Cases of scarlet fever were also seen in Boston during a period of decreasing severity after 1885. Boston City Hospital opened a scarlet fever pavilion in 1887 to house patients with infectious diseases and saw nearly 25,000 patients during 1895–1905. In the mid-1800s, more specific epidemiological information was emerging and incidence in infants were found to be low. In 1870, the US census showed a decrease in scarlet fever mortality in children below the age of one. In the UK, scarlet fever was considered benign for two centuries, but fatal epidemics were seen in the 1700s. Scarlet fever broke out in England in the 19th century and was responsible for an enormous number of deaths in the 60-year period from 1825 to 1885; decades that followed had lower levels of annual mortality from scarlet fever. In NW England there was heavy mortality in Liverpool . Babies born in Liverpool with a birthday in 1861 were only expected to live 26 years, and in larger cities, life expectancy was less than 35 years. Over time, the life expectancy changed as well as the number of fatalities from scarlet fever. There was a reduction in child mortality from scarlet fever when you compare the decades, 1851–60 and 1891–1900. The decline of mortality seen for scarlet fever was noticed after the identification of streptococcus , but the decline was not associated with a treatment. A treatment would not be available until the introduction of sulphonamides in the 1930s, and the decline in mortality was due to the quality of air, food, and water improving. Outbreaks of scarlet fever also took place in Dublin in 1896 with 1,354 cases and 149 deaths, Norway from 1862 to 1884, Scotland in 1861, and in the rest of United Kingdom. The United Kingdom saw cases in Canterbury from 1839 to 1865 with 305 deaths, Bristol in 1870 with 106 deaths and in 1875, and Manchester in 1886 with six cases. Chile reported scarlet fever the first time in 1827 and highest rates were seen during winter months. The disease spread from Valparaiso to Santiago from 1831 to 1832 and claimed 7,000 lives. There were multiple outbreaks in different locations of Chile, including Copaipo in 1875 and Caldera in 1876. Similarly to Europe, America considered scarlet fever to be benign for two centuries. In the early 19th century the scarlet fever impact drastically changed and lethal epidemics started to arise in the United States. The United States had a notable outbreak of scarlet fever in Minnesota in 1847 and Augusta, Georgia had a lethal epidemic in 1832–1833. Scarlet fever had low mortality rates in New York for many years before 1828, but remained high for long after. Cases of scarlet fever were also seen in Boston during a period of decreasing severity after 1885. Boston City Hospital opened a scarlet fever pavilion in 1887 to house patients with infectious diseases and saw nearly 25,000 patients during 1895–1905. In the mid-1800s, more specific epidemiological information was emerging and incidence in infants were found to be low. In 1870, the US census showed a decrease in scarlet fever mortality in children below the age of one.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1881–1896_cholera_pandemic/html

1881–1896 cholera pandemic

The fifth cholera pandemic (1881–1896) was the fifth major international outbreak of cholera in the 19th century. The endemic origin of the pandemic, as had its predecessors, was in the Ganges Delta in West Bengal . While the Vibrio cholerae bacteria had not been able to spread to western Europe until the 19th century, faster and improved modes of modern transportation, such as steamships and railways, reduced the duration of the journey considerably and facilitated the transmission of cholera and other infectious diseases . During the fourth 1863–1875 cholera pandemic , the third International Sanitary Conference convened in 1866 in Constantinople had identified religious pilgrimages to be "the most powerful of all causes" of cholera and again Hindu and Muslim pilgrimages were an important factor in the spread of the disease. In addition, the growing colonial rule of the British in India, and France's colonial war in Indo-China , with its increased military presence and economic exchanges multiplied the connections both inside Asia and between Asia and Europe. Therefore, cholera for the first time could spread significantly outside its original source habitat on the Indian subcontinent, where it had been home for centuries. The fifth cholera pandemic would be known in Europe as the 'eastern plague'. A better insight in the disease and improved sanitation limited mortality largely in Europe and North America, although some substantial outbreaks in Europe did happen. During this pandemic, there were significant scientific advances that improved the control of the disease. German microbiologist Robert Koch isolated Vibrio cholerae and proposed postulates to explain how bacteria caused disease. His work helped to establish the germ theory of disease . In 1892, the Russian-French bacteriologist Waldemar Haffkine , developed a cholera vaccine . (See: Scientific advances )In 1881, the cholera bacterium spread both East and West, and eventually reached Europe and Latin America. From its endemic origin in the Ganges Delta in West Bengal, there was a virulent outbreak in the Punjab and Lahore in northwest India in the years 1881–82, with a very serious death rate. Other early outbreaks occurred in Korea in 1881, and in Thailand in 1882. The Islamic holy city Mecca (Arabia), with its yearly influx of Muslim pilgrims a notorious transmission hub for cholera, was hit during both these years. Further eastward outbreaks occurred in China (also in 1883), and in Japan, followed by the Philippines in 1882–83. In the following years cholera in Asia hit China in 1888, 1890, and 1895; Japan in 1885, 1886, 1890, 1891, and 1895; Korea in 1888, 1890, 1891, and 1895; and the Philippines in 1888–89. In 1883 it reached Egypt and in the course of a few months, tens of thousands of victims died. (Seeː 1883 outbreak in Egypt ) Further westward cholera outbreaks occurred in April 1884 in the naval base Toulon , France, with smaller outbreaks in Marseilles , Paris , and other cities, affecting 10,000 people all over France. In 1885, some of the same areas were again infected. Italian migrant workers brought cholera from France to Italy, with a serious outbreak in the city of Naples in August–September 1884. There were minor outbreaks in Italy in 1886-87 without causing epidemics. The outbreak provoked a poisoning " phobia " directed primarily against Gypsies . The pandemic also spread to Spain , with a minor outbreak starting in Alicante on the Mediterranean coast. But with a more virulent one at the end of 1885, with 160,000 cases and about 60,000 deaths. In 1890 there was another smaller outbreak. According to The New York Times in 1890, cholera had swept away about 120,000 of the inhabitants in the country. Quarantine measures for ships and immigrants based on the findings of the British physician, John Snow , prevented cholera outbreaks in Great Britain and the United States. However, the disease reached Latin America with serious outbreaks in 1886 (Argentina), 1887 (Chile), and 1888 (Argentina and Chile). The pandemic reappeared in 1891 and originated in Bengal when 60,000 Hindu pilgrims arrived at a small village to celebrate a bathing festival unknown to the authorities. The pilgrims caused new immense cholera outbreaks in northern India during 1891, with more than 580,000 cholera deaths in Assam , Bengal, and Uttar Pradesh . The disease continued westward in 1892, across the Punjab (with 75,000 cholera deaths), and raged on through Afghanistan and claimed 60,000 lives in Persia , and then reached Imperial Russia which suffered a staggering morbidity rate, exacerbated by the Russian famine of 1891–1892 . Cholera's penetration in Russia began at Baku , a port on the Caspian Sea . The disease spread upstream along the Volga to reach Moscow and St. Petersburg , where morbidity was relatively minor. The official death toll for 1892 was 300,321. The epidemic faded during the winter and 42,250 cholera deaths were recorded in 1893. The busy ports of Hamburg in Germany (Seeː 1892 outbreak in Hamburg ), and New York City , the main exit and entry points for cross Atlantic emigration from Europe to the United States, were hit by serious cholera outbreaks in 1892. New York, the busiest port of the U.S. was hit by a combination of typhus fever and cholera in 1892 through Hamburg. The main source of those epidemics were East European Jews, mainly from Imperial Russia, that tried to escape the appalling conditions, the 1891–1892 famine, and antisemitic restrictions (such as the expulsion of Jews from Moscow early in 1892) in their home country. In Europe in 1892, the disease was alo prevalent in France. Germany and France were reinfected in 1893-94 but outbreaks did not reach epidemic levels. Latin America again suffered attacks several times in the 1890s. Brazil was hit with cholera in 1893–95, mainly along the railway in the Paraíba Valley , through ships carrying immigrants from Europe, Argentina in 1894–95, and Uruguay in 1895. The pandemic also reached the African continent, with outbreaks in 1893 ( Tripolitania , Tunisia , Algeria , Morocco , and French West Africa ), 1894 ( Sudan , Tripolitania, and French West Africa), 1895 (Morocco and Egypt), and 1896 (Egypt). In the following years there were no new cholera outbreaks, but in 1899 it broke out again in many regions, leading to the 1899–1923 cholera pandemic . In late June 1883, the first cases of cholera in Egypt, recently occupied by the British Empire in 1882, occurred in the port city of Damietta on the Mediterranean coast and rapidly spread in the Nile Delta and throughout the country in the summer and autumn, "notwithstanding cordons maintained with a degree of severity and cruelty almost unexampled". In the course of a few months, according to different estimates between 50,000 and 60,000 people died. The sources of the contamination most likely were Muslim pilgrims returning from Mecca and Indian troops serving in the British army. French and German bacteriologists were sent to Alexandria in 1883 to study the disease and determine its cause. (See: Scientific advances ) The approach of the British administration in Egypt was determined more by concerns that trade out of Indian ports towards Britain risked to be quarantined, as well as economic concerns about spending on public health. The rapid spread of the disease and the perceived incompetence of the population were used to justify British control of Egypt, despite that Egypt's established pre-colonial national health system had been talked about with appreciation by European observers. However, the imposed anti-contagionist policies by the British administration, favouring British shareholders in Egyptian and Indian companies and shipping lines, contributed to the lack of effective measures to combat the 1883 epidemic. Containing the epidemic was further complicated by European prejudices influenced by Orientalism that discredited the understanding by "Orientals" of health, science, and hygiene. From mid-August to mid-September 1892 the city of Hamburg , Germany, was hit by a cholera epidemic. The main source of the outbreak were East European Jews, mainly from Imperial Russia, that were on their way to cross the Atlantic Ocean, trying to escape the appalling conditions, the 1891–1892 famine and cholera epidemic, and antisemitic restrictions (such as the expulsion of Jews from Moscow early in 1892) in their home country. Before they boarded, the emigrants were housed in special barracks, jointly financed by the city and the Hamburg America Line shipping company, that were built in the harbour. Conditions were often inadequate and communal latrines discharged their untreated excrement directly into the Elbe river flowing through the city. In just two months, 8,594 people died. According to other estimates nearly 10,000 people died and many more suffered the appalling symptoms of the disease. No other city in western Europe was as seriously affected in this wave of the pandemic, with an average of 140 per day. Although at the time it was fiercely contested, the infection of the city's water-supply was the main reason for the rapid spread of the cholera. Of those infected the case-mortality was about 50 per cent. The death rate of Hamburg's total population of approximately 66,000 was 13.4 per cent according to the official statistics, but it may have even been higher. In 1893 violent riots broke out, because the public objected to sanitary officers trying to enforce regulations for the prevention of spread of the disease. The crowd beat to death a sanitary officer and one of the policemen sent to protect them. Troops were called out and dispersed the crowd with fixed bayonets. American author Mark Twain visited Hamburg during the outbreak. In a piece dated 1891–1892, he points out the insufficient information in local newspapers about the outbreak, particularly regarding death figures. Twain criticizes how impoverished individuals were forcefully moved to pest houses where many perished unrecognized and unceremoniously buried. Twain said that people were "snatched from their homes to the pest houses", where "a good many of them ... die unknown and are buried so". He expresses disappointment at the global, and specifically American, lack of awareness concerning cholera. In late June 1883, the first cases of cholera in Egypt, recently occupied by the British Empire in 1882, occurred in the port city of Damietta on the Mediterranean coast and rapidly spread in the Nile Delta and throughout the country in the summer and autumn, "notwithstanding cordons maintained with a degree of severity and cruelty almost unexampled". In the course of a few months, according to different estimates between 50,000 and 60,000 people died. The sources of the contamination most likely were Muslim pilgrims returning from Mecca and Indian troops serving in the British army. French and German bacteriologists were sent to Alexandria in 1883 to study the disease and determine its cause. (See: Scientific advances ) The approach of the British administration in Egypt was determined more by concerns that trade out of Indian ports towards Britain risked to be quarantined, as well as economic concerns about spending on public health. The rapid spread of the disease and the perceived incompetence of the population were used to justify British control of Egypt, despite that Egypt's established pre-colonial national health system had been talked about with appreciation by European observers. However, the imposed anti-contagionist policies by the British administration, favouring British shareholders in Egyptian and Indian companies and shipping lines, contributed to the lack of effective measures to combat the 1883 epidemic. Containing the epidemic was further complicated by European prejudices influenced by Orientalism that discredited the understanding by "Orientals" of health, science, and hygiene. From mid-August to mid-September 1892 the city of Hamburg , Germany, was hit by a cholera epidemic. The main source of the outbreak were East European Jews, mainly from Imperial Russia, that were on their way to cross the Atlantic Ocean, trying to escape the appalling conditions, the 1891–1892 famine and cholera epidemic, and antisemitic restrictions (such as the expulsion of Jews from Moscow early in 1892) in their home country. Before they boarded, the emigrants were housed in special barracks, jointly financed by the city and the Hamburg America Line shipping company, that were built in the harbour. Conditions were often inadequate and communal latrines discharged their untreated excrement directly into the Elbe river flowing through the city. In just two months, 8,594 people died. According to other estimates nearly 10,000 people died and many more suffered the appalling symptoms of the disease. No other city in western Europe was as seriously affected in this wave of the pandemic, with an average of 140 per day. Although at the time it was fiercely contested, the infection of the city's water-supply was the main reason for the rapid spread of the cholera. Of those infected the case-mortality was about 50 per cent. The death rate of Hamburg's total population of approximately 66,000 was 13.4 per cent according to the official statistics, but it may have even been higher. In 1893 violent riots broke out, because the public objected to sanitary officers trying to enforce regulations for the prevention of spread of the disease. The crowd beat to death a sanitary officer and one of the policemen sent to protect them. Troops were called out and dispersed the crowd with fixed bayonets. American author Mark Twain visited Hamburg during the outbreak. In a piece dated 1891–1892, he points out the insufficient information in local newspapers about the outbreak, particularly regarding death figures. Twain criticizes how impoverished individuals were forcefully moved to pest houses where many perished unrecognized and unceremoniously buried. Twain said that people were "snatched from their homes to the pest houses", where "a good many of them ... die unknown and are buried so". He expresses disappointment at the global, and specifically American, lack of awareness concerning cholera. French and German bacteriologists were sent to Alexandria, Egypt in 1883 to study the cholera epidemic and determine its cause. In August 1883, the German government sent a medical team led by Robert Koch . As the outbreak in Egypt declined, he was transferred to Calcutta (now Kolkata ) India, where there was a more severe outbreak. He soon found that the river Ganges was the source of cholera. He performed autopsies of almost 100 bodies, and found in each bacterial infection. He identified the same bacteria from water tanks, linking the source of the infection. Koch isolated Vibrio cholerae and proposed postulates to explain how bacteria caused disease. His work helped to establish the germ theory of disease . Not everyone agreed with Koch's findings. On 20 May 1885, the sixth International Sanitary Conference was convened in Rome by the Italian government following the reappearance of cholera. At the conference, with 28 government delegations present, the British delegation successfully blocked any "theoretical discussion on the etiology of cholera," despite Koch himself being one of the German delegates. Due to the failures in containing the disease, the conference reaffirmed the futility of a cordon sanitaire in the fight against cholera. Prior to this time, many physicians believed the disease was caused by direct exposure to the products of filth and decay. Koch helped establish that the disease was more specifically contagious and was transmitted by exposure to the feces of an infected person, including through contaminated water supply. Koch's discoveries led to extensive research into water and wastewater treatment. The germ theory of cholera introduced new methods of protection against the disease, such as the use of chemical disinfectants and heat to kill the bacillus (by boiling water, for instance). Better ways of treating patients were also developed to prevent cholera from spreading further. Waldemar Haffkine , a Russian-French bacteriologist , focused his research on developing a cholera vaccine, and produced an attenuated form of the bacterium. Risking his own life, on 18 July 1892, Haffkine performed the first human test on himself. To definitively test the vaccine, he needed an area where cholera was common to conduct large trials on humans and moved to India in 1894. After Haffkine's experiments in Calcutta showed promising results, he was asked by the owners of tea plantations in Assam to vaccinate their workers.

Wiki

Cholera

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

Miasma theory

The miasma theory (also called the miasmic theory ) is an abandoned medical theory that held that diseases —such as cholera , chlamydia , or the Black Death —were caused by a miasma ( μίασμα , Ancient Greek for 'pollution'), a noxious form of "bad air", also known as night air . The theory held that epidemics were caused by miasma, emanating from rotting organic matter. Though miasma theory is typically associated with the spread of contagious diseases, some academics in the early nineteenth century suggested that the theory extended to other conditions as well, e.g. one could become obese by inhaling the odor of food. The miasma theory was advanced by Hippocrates in the fourth century B.C. and accepted from ancient times in Europe and China . The theory was eventually abandoned by scientists and physicians after 1880, replaced by the germ theory of disease : specific germs, not miasma, caused specific diseases. However, cultural beliefs about getting rid of odor made the clean-up of waste a high priority for cities. It also encouraged the construction of well-ventilated hospital facilities, schools and other buildings. The word miasma comes from ancient Greek and though conceptually, there is no word in English that has the same exact meaning, it can be loosely translated as 'stain' or 'pollution'. The idea also gave rise to the name malaria (literally 'bad air') through medieval Italian.Miasma was considered to be a poisonous vapor or mist filled with particles from decomposed matter (miasmata) that caused illnesses. The miasmatic position was that diseases were the product of environmental factors such as contaminated water, foul air, and poor hygienic conditions. Such infection was not passed between individuals but would affect individuals within the locale that gave rise to such vapors. It was identifiable by its foul smell. It was also initially believed that miasmas were propagated through worms from ulcers within those affected by a plague. In the fifth or fourth century BC, Hippocrates wrote about the effects of the environs over the human diseases: Whoever wishes to investigate medicine properly, should proceed thus: in the first place to consider the seasons of the year, and what effects each of them produces for they are not at all alike, but differ much from themselves in regard to their changes. Then the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality. We must also consider the qualities of the waters, for as they differ from one another in taste and weight, so also do they differ much in their qualities. In the same manner, when one comes into a city to which he is a stranger, he ought to consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or the south, to the rising or to the setting sun. These things one ought to consider most attentively, and concerning the waters which the inhabitants use, whether they be marshy and soft, or hard, and running from elevated and rocky situations, and then if saltish and unfit for cooking; and the ground, whether it be naked and deficient in water, or wooded and well watered, and whether it lies in a hollow, confined situation, or is elevated and cold; and the mode in which the inhabitants live, and what are their pursuits, whether they are fond of drinking and eating to excess, and given to indolence, or are fond of exercise and labor, and not given to excess in eating and drinking. In the 1st century BC, the Roman architectural writer Vitruvius described the potential effects of miasma ( Latin nebula ) from fetid swamplands when visiting a city: For when the morning breezes blow toward the town at sunrise, if they bring with them mist from marshes and, mingled with the mist, the poisonous breath of creatures of the marshes to be wafted into the bodies of the inhabitants, they will make the site unhealthy. The miasmatic theory of disease remained popular in the Middle Ages and a sense of effluvia contributed to Robert Boyle's Suspicions about the Hidden Realities of the Air . In the 1850s, miasma was used to explain the spread of cholera in London and in Paris , partly justifying Haussmann's later renovation of the French capital . The disease was said to be preventable by cleansing and scouring of the body and items. Dr. William Farr , the assistant commissioner for the 1851 London census, was an important supporter of the miasma theory. He believed that cholera was transmitted by air, and that there was a deadly concentration of miasmata near the River Thames ' banks. Such a belief was in part accepted because of the general lack of air quality in urbanized areas. The wide acceptance of miasma theory during the cholera outbreaks overshadowed the partially correct theory brought forth by John Snow that cholera was spread through water. This slowed the response to the major outbreaks in the Soho district of London and other areas. The Crimean War nurse Florence Nightingale (1820–1910) was a proponent of the theory and worked to make hospitals sanitary and fresh-smelling. It was stated in 'Notes on Nursing for the Labouring Classes' (1860) that Nightingale would "keep the air [the patient] breathes as pure as the external air." Fear of miasma registered in many early nineteenth-century warnings concerning what was termed "unhealthy fog". The presence of fog was thought to strongly indicate the presence of miasma. The miasmas were thought to behave like smoke or mist, blown with air currents, wafted by winds. It was thought that miasma didn't simply travel on air but changed the air through which it propagated; the atmosphere was infected by miasma, as diseased people were. In China, miasma ( Chinese : 瘴氣 ; pinyin : Zhà ngqì ; alternative names 瘴毒 , 瘴癘 ) is an old concept of illness, used extensively by ancient Chinese local chronicles and works of literature. Miasma has different names in Chinese culture. Most of the explanations of miasma refer to it as a kind of sickness, or poison gas. The ancient Chinese thought that miasma was related to the environment of parts of Southern China. The miasma was thought to be caused by the heat, moisture and the dead air in the Southern Chinese mountains. They thought that insects' waste polluted the air, the fog, and the water, and the virgin forest harbored a great environment for miasma to occur. In descriptions by ancient travelers, soldiers, or local officials (most of them are men of letters) of the phenomenon of miasma, fog, haze, dust, gas, or poison geological gassing were always mentioned. The miasma was thought to have caused a lot of diseases such as the cold, influenza, heat strokes, malaria , or dysentery. In the medical history of China, malaria had been referred to by different names in different dynasty periods. Poisoning and psittacosis were also called miasma in ancient China because they did not accurately understand the cause of disease. In the Sui dynasty , doctor Chao Yuanfang mentioned miasma in his book On Pathogen and Syndromes ( è«¸ç— æºå€™è«– ). He thought that miasma in Southern China was similar to typhoid fever in Northern China. However, in his opinion, miasma was different from malaria and dysentery . In his book, he discussed dysentery in another chapter, and malaria in a single chapter. He also claimed that miasma caused various diseases, so he suggested that one should find apt and specific ways to resolve problems. The concept of miasma developed in several stages. First, before the Western Jin dynasty , the concept of miasma was gradually forming; at least, in the Eastern Han dynasty , there was no description of miasma. During the Eastern Jin, large numbers of northern people moved south, and miasma was then recognized by men of letters and nobility. After the Sui and the Tang dynasty , scholars-bureaucrats sent to be the local officials recorded and investigated miasma. As a result, the government became concerned about the severe cases and the causes of miasma by sending doctors to the areas of epidemic to research the disease and heal the patients. In the Ming dynasty and Qing dynasty , versions of local chronicles record different miasma in different places. However, Southern China was highly developed in the Ming and Qing dynasties. The environment changed rapidly, and after the 19th century, western science and medical knowledge were introduced into China, and people knew how to distinguish and deal with the disease. The concept of miasma therefore faded out due to the progress of medicine in China. The terrifying miasma diseases in the southern regions of China made it the primary location for relegating officials and sending criminals to exile since the Qin-Han dynasty. Poet Han Yu ( 韓愈 ) of the Tang dynasty , for example, wrote to his nephew who came to see him off after his banishment to the Chao Prefecture in his poem, En Route ( 左遷至藍關示姪孫湘 ): At dawn I sent a single warning to the throne of the Nine Steps; At evening I was banished to Chao Yang, eight thousand leagues. Striving on behalf of a noble dynasty to expel an ignoble government, How should I, withered and worn, deplore my future lot? The clouds gather on Ch'in Mountains, I cannot see my home; The snow bars the passes of Lan, my horse cannot go forward. But I know that you will come from afar, to fulfil your set purpose, And lovingly gather my bones, on the banks of that plague-stricken river. The prevalent belief and predominant fear of the southern region with its "poisonous air and gases" is evident in historical documents. Similar topics and feelings toward the miasma-infected south are often reflected in early Chinese poetry and records. Most scholars of the time agreed that the geological environments in the south had a direct impact on the population composition and growth. Many historical records reflect that females were less prone to miasma infection, and mortality rates were much higher in the south, especially for the men. This directly influenced agriculture cultivation and the southern economy, as men were the engine of agriculture production. Zhou Qufei ( 周去非 ), a local magistrate from the Southern Song dynasty , described in his treatise Representative Answers from the South : "... The men are short and tan, while the women were plump and seldom came down with illness," and exclaimed at the populous female population in the Guangxi region. This inherent environmental threat also prevented immigration from other regions. Hence, development in the damp and sultry south was much slower than in the north, where the dynasties' political power resided for much of early Chinese history. In India , there was also a miasma theory. Gambir was considered the first antimiasmatic application. This gambir tree is found in Southern India and Sri Lanka. [ better source needed ]In the fifth or fourth century BC, Hippocrates wrote about the effects of the environs over the human diseases: Whoever wishes to investigate medicine properly, should proceed thus: in the first place to consider the seasons of the year, and what effects each of them produces for they are not at all alike, but differ much from themselves in regard to their changes. Then the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality. We must also consider the qualities of the waters, for as they differ from one another in taste and weight, so also do they differ much in their qualities. In the same manner, when one comes into a city to which he is a stranger, he ought to consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or the south, to the rising or to the setting sun. These things one ought to consider most attentively, and concerning the waters which the inhabitants use, whether they be marshy and soft, or hard, and running from elevated and rocky situations, and then if saltish and unfit for cooking; and the ground, whether it be naked and deficient in water, or wooded and well watered, and whether it lies in a hollow, confined situation, or is elevated and cold; and the mode in which the inhabitants live, and what are their pursuits, whether they are fond of drinking and eating to excess, and given to indolence, or are fond of exercise and labor, and not given to excess in eating and drinking. In the 1st century BC, the Roman architectural writer Vitruvius described the potential effects of miasma ( Latin nebula ) from fetid swamplands when visiting a city: For when the morning breezes blow toward the town at sunrise, if they bring with them mist from marshes and, mingled with the mist, the poisonous breath of creatures of the marshes to be wafted into the bodies of the inhabitants, they will make the site unhealthy. The miasmatic theory of disease remained popular in the Middle Ages and a sense of effluvia contributed to Robert Boyle's Suspicions about the Hidden Realities of the Air . In the 1850s, miasma was used to explain the spread of cholera in London and in Paris , partly justifying Haussmann's later renovation of the French capital . The disease was said to be preventable by cleansing and scouring of the body and items. Dr. William Farr , the assistant commissioner for the 1851 London census, was an important supporter of the miasma theory. He believed that cholera was transmitted by air, and that there was a deadly concentration of miasmata near the River Thames ' banks. Such a belief was in part accepted because of the general lack of air quality in urbanized areas. The wide acceptance of miasma theory during the cholera outbreaks overshadowed the partially correct theory brought forth by John Snow that cholera was spread through water. This slowed the response to the major outbreaks in the Soho district of London and other areas. The Crimean War nurse Florence Nightingale (1820–1910) was a proponent of the theory and worked to make hospitals sanitary and fresh-smelling. It was stated in 'Notes on Nursing for the Labouring Classes' (1860) that Nightingale would "keep the air [the patient] breathes as pure as the external air." Fear of miasma registered in many early nineteenth-century warnings concerning what was termed "unhealthy fog". The presence of fog was thought to strongly indicate the presence of miasma. The miasmas were thought to behave like smoke or mist, blown with air currents, wafted by winds. It was thought that miasma didn't simply travel on air but changed the air through which it propagated; the atmosphere was infected by miasma, as diseased people were. In China, miasma ( Chinese : 瘴氣 ; pinyin : Zhà ngqì ; alternative names 瘴毒 , 瘴癘 ) is an old concept of illness, used extensively by ancient Chinese local chronicles and works of literature. Miasma has different names in Chinese culture. Most of the explanations of miasma refer to it as a kind of sickness, or poison gas. The ancient Chinese thought that miasma was related to the environment of parts of Southern China. The miasma was thought to be caused by the heat, moisture and the dead air in the Southern Chinese mountains. They thought that insects' waste polluted the air, the fog, and the water, and the virgin forest harbored a great environment for miasma to occur. In descriptions by ancient travelers, soldiers, or local officials (most of them are men of letters) of the phenomenon of miasma, fog, haze, dust, gas, or poison geological gassing were always mentioned. The miasma was thought to have caused a lot of diseases such as the cold, influenza, heat strokes, malaria , or dysentery. In the medical history of China, malaria had been referred to by different names in different dynasty periods. Poisoning and psittacosis were also called miasma in ancient China because they did not accurately understand the cause of disease. In the Sui dynasty , doctor Chao Yuanfang mentioned miasma in his book On Pathogen and Syndromes ( è«¸ç— æºå€™è«– ). He thought that miasma in Southern China was similar to typhoid fever in Northern China. However, in his opinion, miasma was different from malaria and dysentery . In his book, he discussed dysentery in another chapter, and malaria in a single chapter. He also claimed that miasma caused various diseases, so he suggested that one should find apt and specific ways to resolve problems. The concept of miasma developed in several stages. First, before the Western Jin dynasty , the concept of miasma was gradually forming; at least, in the Eastern Han dynasty , there was no description of miasma. During the Eastern Jin, large numbers of northern people moved south, and miasma was then recognized by men of letters and nobility. After the Sui and the Tang dynasty , scholars-bureaucrats sent to be the local officials recorded and investigated miasma. As a result, the government became concerned about the severe cases and the causes of miasma by sending doctors to the areas of epidemic to research the disease and heal the patients. In the Ming dynasty and Qing dynasty , versions of local chronicles record different miasma in different places. However, Southern China was highly developed in the Ming and Qing dynasties. The environment changed rapidly, and after the 19th century, western science and medical knowledge were introduced into China, and people knew how to distinguish and deal with the disease. The concept of miasma therefore faded out due to the progress of medicine in China. The terrifying miasma diseases in the southern regions of China made it the primary location for relegating officials and sending criminals to exile since the Qin-Han dynasty. Poet Han Yu ( 韓愈 ) of the Tang dynasty , for example, wrote to his nephew who came to see him off after his banishment to the Chao Prefecture in his poem, En Route ( 左遷至藍關示姪孫湘 ): At dawn I sent a single warning to the throne of the Nine Steps; At evening I was banished to Chao Yang, eight thousand leagues. Striving on behalf of a noble dynasty to expel an ignoble government, How should I, withered and worn, deplore my future lot? The clouds gather on Ch'in Mountains, I cannot see my home; The snow bars the passes of Lan, my horse cannot go forward. But I know that you will come from afar, to fulfil your set purpose, And lovingly gather my bones, on the banks of that plague-stricken river. The prevalent belief and predominant fear of the southern region with its "poisonous air and gases" is evident in historical documents. Similar topics and feelings toward the miasma-infected south are often reflected in early Chinese poetry and records. Most scholars of the time agreed that the geological environments in the south had a direct impact on the population composition and growth. Many historical records reflect that females were less prone to miasma infection, and mortality rates were much higher in the south, especially for the men. This directly influenced agriculture cultivation and the southern economy, as men were the engine of agriculture production. Zhou Qufei ( 周去非 ), a local magistrate from the Southern Song dynasty , described in his treatise Representative Answers from the South : "... The men are short and tan, while the women were plump and seldom came down with illness," and exclaimed at the populous female population in the Guangxi region. This inherent environmental threat also prevented immigration from other regions. Hence, development in the damp and sultry south was much slower than in the north, where the dynasties' political power resided for much of early Chinese history. The terrifying miasma diseases in the southern regions of China made it the primary location for relegating officials and sending criminals to exile since the Qin-Han dynasty. Poet Han Yu ( 韓愈 ) of the Tang dynasty , for example, wrote to his nephew who came to see him off after his banishment to the Chao Prefecture in his poem, En Route ( 左遷至藍關示姪孫湘 ): At dawn I sent a single warning to the throne of the Nine Steps; At evening I was banished to Chao Yang, eight thousand leagues. Striving on behalf of a noble dynasty to expel an ignoble government, How should I, withered and worn, deplore my future lot? The clouds gather on Ch'in Mountains, I cannot see my home; The snow bars the passes of Lan, my horse cannot go forward. But I know that you will come from afar, to fulfil your set purpose, And lovingly gather my bones, on the banks of that plague-stricken river. The prevalent belief and predominant fear of the southern region with its "poisonous air and gases" is evident in historical documents. Similar topics and feelings toward the miasma-infected south are often reflected in early Chinese poetry and records. Most scholars of the time agreed that the geological environments in the south had a direct impact on the population composition and growth. Many historical records reflect that females were less prone to miasma infection, and mortality rates were much higher in the south, especially for the men. This directly influenced agriculture cultivation and the southern economy, as men were the engine of agriculture production. Zhou Qufei ( 周去非 ), a local magistrate from the Southern Song dynasty , described in his treatise Representative Answers from the South : "... The men are short and tan, while the women were plump and seldom came down with illness," and exclaimed at the populous female population in the Guangxi region. This inherent environmental threat also prevented immigration from other regions. Hence, development in the damp and sultry south was much slower than in the north, where the dynasties' political power resided for much of early Chinese history. In India , there was also a miasma theory. Gambir was considered the first antimiasmatic application. This gambir tree is found in Southern India and Sri Lanka. [ better source needed ]Based on zymotic theory, people believed vapors called miasmata (singular: miasma ) rose from the soil and spread diseases. Miasmata were believed to come from rotting vegetation and foul water—especially in swamps and urban ghettos . Many people, especially the weak or infirm, avoided breathing night air by going indoors and keeping windows and doors shut. In addition to ideas associated with zymotic theory, there was also a general fear that cold or cool air spread disease. The fear of night air gradually disappeared as understanding about disease increased as well as with improvements in home heating and ventilation. Particularly important was the understanding that the agent spreading malaria was the mosquito (active at night) rather than miasmata. Prior to the late 19th century, night air was considered dangerous in most Western cultures. Throughout the 19th century, the medical community was divided on the explanation for disease proliferation. On one side were the contagionists, believing disease was passed through physical contact, while others believed disease was present in the air in the form of miasma, and thus could proliferate without physical contact. Two members of the latter group were Dr. Thomas S. Smith and Florence Nightingale. Thomas Southwood Smith spent many years comparing the miasmatic theory to contagionism. To assume the method of propagation by touch, whether by the person or of infected articles, and to overlook that by the corruption of the air, is at once to increase the real danger, from exposure to noxious effluvia, and to divert attention from the true means of remedy and prevention. Florence Nightingale : The idea of "contagion", as explaining the spread of disease, appears to have been adopted at a time when, from the neglect of sanitary arrangements, epidemics attacked whole masses of people, and when men had ceased to consider that nature had any laws for her guidance. Beginning with the poets and historians, the word finally made its way into scientific nomenclature, where it has remained ever since [...] a satisfactory explanation for pestilence and an adequate excuse for non-exertion to prevent its recurrence. The current germ theory accounts for disease proliferation by both direct and indirect physical contact. In the early 19th century, the living conditions in industrialized cities in Britain were increasingly unsanitary. The population was growing at a much faster rate than the infrastructure could support. For example, the population of Manchester doubled within a single decade, leading to overcrowding and a significant increase in waste accumulation. The miasma theory of disease made sense to the sanitary reformers of the mid-19th century. Miasmas explained why cholera and other diseases were epidemic in places where the water was stagnant and foul-smelling. A leading sanitary reformer, London's Edwin Chadwick , asserted that "all smell is disease", and maintained that a fundamental change in the structure of sanitation systems was needed to combat increasing urban mortality rates. Chadwick saw the problem of cholera and typhoid epidemics as being directly related to urbanization, and he proposed that new, independent sewerage systems should be connected to homes. Chadwick supported his proposal with reports from the London Statistical Society which showed dramatic increases in both morbidity and mortality rates since the beginning of urbanization in the early 19th century. Though Chadwick proposed reform on the basis of the miasma theory, his proposals did contribute to improvements in sanitation , such as preventing the reflux of noxious air from sewers back into houses by using separate drainage systems in the design of sanitation. That led, incidentally, to decreased outbreaks of cholera and thus helped to support the theory. The miasma theory was consistent with the observation that disease was associated with poor sanitation, and hence foul odours, and that sanitary improvements reduced disease. However, it was inconsistent with the findings arising from microbiology and bacteriology in the later 19th century, which eventually led to the adoption of the germ theory of disease , although consensus was not reached immediately. Concerns over sewer gas , which was a major component of the miasma theory developed by Galen , and brought to prominence by the " Great Stink " in London in the summer of 1858, led proponents of the theory to observe that sewers enclosed the refuse of the human bowel, which medical science had discovered could teem with typhoid , cholera, and other microbes . In 1846, the Nuisances Removal and Diseases Prevention Act was passed to identify whether the transmission of cholera was by air or by water. The act was used to encourage owners to clean their dwellings and connect them to sewers. [ citation needed ] Even though eventually disproved by the understanding of bacteria and the discovery of viruses , the miasma theory helped establish the connection between poor sanitation and disease. That encouraged cleanliness and spurred public health reforms which, in Britain, led to the Public Health Acts of 1848 and 1858, and the Local Government Act of 1858. The latter of those enabled the instituting of investigations into the health and sanitary regulations of any town or place, upon the petition of residents or as a result of death rates exceeding the norm. Early medical and sanitary engineering reformers included Henry Austin, Joseph Bazalgette , Edwin Chadwick , Frank Forster, Thomas Hawksley , William Haywood , Henry Letheby , Robert Rawlinson , John Simon , John Snow and Thomas Wicksteed . Their efforts, and associated British regulatory improvements, were reported in the United States as early as 1865. Particularly notable in 19th century sanitation reform is the work of Joseph Bazalgette, chief engineer to London's Metropolitan Board of Works . Encouraged by the Great Stink, Parliament sanctioned Bazalgette to design and construct a comprehensive system of sewers, which intercepted London's sewage and diverted it away from its water supply. The system helped purify London's water and saved the city from epidemics. In 1866, the last of the three great British cholera epidemics took hold in a small area of Whitechapel . However, the area was not yet connected to Bazalgette's system, and the confined area of the epidemic acted as testament to the efficiency of the system's design. Years later, the influence of those sanitary reforms on Britain was described by Richard Rogers : London was the first city to create a complex civic administration which could coordinate modern urban services, from public transport to housing, clean water to education. London's County Council was acknowledged as the most progressive metropolitan government in the world. Fifty years earlier, London had been the worst slum city of the industrialized world: over-crowded, congested, polluted and ridden with disease... The miasma theory did contribute to containing disease in urban settlements, but did not allow the adoption of a suitable approach to the reuse of excreta in agriculture. It was a major factor in the practice of collecting human excreta from urban settlements and reusing them in the surrounding farmland. That type of resource recovery scheme was common in major cities in the 19th century before the introduction of sewer-based sanitation systems. Nowadays, the reuse of excreta, when done in a hygienic manner, is known as ecological sanitation , and is promoted as a way of "closing the loop". Throughout the 19th century, concern about public health and sanitation, along with the influence of the miasma theory, were reasons for the advocacy of the then-controversial practice of cremation . If infectious diseases were spread by noxious gases emitted from decaying organic matter, that included decaying corpses. The public health argument for cremation faded with the eclipsing of the miasma theory of disease. Based on zymotic theory, people believed vapors called miasmata (singular: miasma ) rose from the soil and spread diseases. Miasmata were believed to come from rotting vegetation and foul water—especially in swamps and urban ghettos . Many people, especially the weak or infirm, avoided breathing night air by going indoors and keeping windows and doors shut. In addition to ideas associated with zymotic theory, there was also a general fear that cold or cool air spread disease. The fear of night air gradually disappeared as understanding about disease increased as well as with improvements in home heating and ventilation. Particularly important was the understanding that the agent spreading malaria was the mosquito (active at night) rather than miasmata. Prior to the late 19th century, night air was considered dangerous in most Western cultures. Throughout the 19th century, the medical community was divided on the explanation for disease proliferation. On one side were the contagionists, believing disease was passed through physical contact, while others believed disease was present in the air in the form of miasma, and thus could proliferate without physical contact. Two members of the latter group were Dr. Thomas S. Smith and Florence Nightingale. Thomas Southwood Smith spent many years comparing the miasmatic theory to contagionism. To assume the method of propagation by touch, whether by the person or of infected articles, and to overlook that by the corruption of the air, is at once to increase the real danger, from exposure to noxious effluvia, and to divert attention from the true means of remedy and prevention. Florence Nightingale : The idea of "contagion", as explaining the spread of disease, appears to have been adopted at a time when, from the neglect of sanitary arrangements, epidemics attacked whole masses of people, and when men had ceased to consider that nature had any laws for her guidance. Beginning with the poets and historians, the word finally made its way into scientific nomenclature, where it has remained ever since [...] a satisfactory explanation for pestilence and an adequate excuse for non-exertion to prevent its recurrence. The current germ theory accounts for disease proliferation by both direct and indirect physical contact.In the early 19th century, the living conditions in industrialized cities in Britain were increasingly unsanitary. The population was growing at a much faster rate than the infrastructure could support. For example, the population of Manchester doubled within a single decade, leading to overcrowding and a significant increase in waste accumulation. The miasma theory of disease made sense to the sanitary reformers of the mid-19th century. Miasmas explained why cholera and other diseases were epidemic in places where the water was stagnant and foul-smelling. A leading sanitary reformer, London's Edwin Chadwick , asserted that "all smell is disease", and maintained that a fundamental change in the structure of sanitation systems was needed to combat increasing urban mortality rates. Chadwick saw the problem of cholera and typhoid epidemics as being directly related to urbanization, and he proposed that new, independent sewerage systems should be connected to homes. Chadwick supported his proposal with reports from the London Statistical Society which showed dramatic increases in both morbidity and mortality rates since the beginning of urbanization in the early 19th century. Though Chadwick proposed reform on the basis of the miasma theory, his proposals did contribute to improvements in sanitation , such as preventing the reflux of noxious air from sewers back into houses by using separate drainage systems in the design of sanitation. That led, incidentally, to decreased outbreaks of cholera and thus helped to support the theory. The miasma theory was consistent with the observation that disease was associated with poor sanitation, and hence foul odours, and that sanitary improvements reduced disease. However, it was inconsistent with the findings arising from microbiology and bacteriology in the later 19th century, which eventually led to the adoption of the germ theory of disease , although consensus was not reached immediately. Concerns over sewer gas , which was a major component of the miasma theory developed by Galen , and brought to prominence by the " Great Stink " in London in the summer of 1858, led proponents of the theory to observe that sewers enclosed the refuse of the human bowel, which medical science had discovered could teem with typhoid , cholera, and other microbes . In 1846, the Nuisances Removal and Diseases Prevention Act was passed to identify whether the transmission of cholera was by air or by water. The act was used to encourage owners to clean their dwellings and connect them to sewers. [ citation needed ] Even though eventually disproved by the understanding of bacteria and the discovery of viruses , the miasma theory helped establish the connection between poor sanitation and disease. That encouraged cleanliness and spurred public health reforms which, in Britain, led to the Public Health Acts of 1848 and 1858, and the Local Government Act of 1858. The latter of those enabled the instituting of investigations into the health and sanitary regulations of any town or place, upon the petition of residents or as a result of death rates exceeding the norm. Early medical and sanitary engineering reformers included Henry Austin, Joseph Bazalgette , Edwin Chadwick , Frank Forster, Thomas Hawksley , William Haywood , Henry Letheby , Robert Rawlinson , John Simon , John Snow and Thomas Wicksteed . Their efforts, and associated British regulatory improvements, were reported in the United States as early as 1865. Particularly notable in 19th century sanitation reform is the work of Joseph Bazalgette, chief engineer to London's Metropolitan Board of Works . Encouraged by the Great Stink, Parliament sanctioned Bazalgette to design and construct a comprehensive system of sewers, which intercepted London's sewage and diverted it away from its water supply. The system helped purify London's water and saved the city from epidemics. In 1866, the last of the three great British cholera epidemics took hold in a small area of Whitechapel . However, the area was not yet connected to Bazalgette's system, and the confined area of the epidemic acted as testament to the efficiency of the system's design. Years later, the influence of those sanitary reforms on Britain was described by Richard Rogers : London was the first city to create a complex civic administration which could coordinate modern urban services, from public transport to housing, clean water to education. London's County Council was acknowledged as the most progressive metropolitan government in the world. Fifty years earlier, London had been the worst slum city of the industrialized world: over-crowded, congested, polluted and ridden with disease... The miasma theory did contribute to containing disease in urban settlements, but did not allow the adoption of a suitable approach to the reuse of excreta in agriculture. It was a major factor in the practice of collecting human excreta from urban settlements and reusing them in the surrounding farmland. That type of resource recovery scheme was common in major cities in the 19th century before the introduction of sewer-based sanitation systems. Nowadays, the reuse of excreta, when done in a hygienic manner, is known as ecological sanitation , and is promoted as a way of "closing the loop". Throughout the 19th century, concern about public health and sanitation, along with the influence of the miasma theory, were reasons for the advocacy of the then-controversial practice of cremation . If infectious diseases were spread by noxious gases emitted from decaying organic matter, that included decaying corpses. The public health argument for cremation faded with the eclipsing of the miasma theory of disease. Although the connection between germ and disease was proposed quite early, it was not until the late 1800s that the germ theory was generally accepted. The miasmatic theory was challenged by John Snow , suggesting that there was some means by which the disease was spread via a poison or morbid material (orig: materies morbi ) in the water. He suggested this before and in response to a cholera epidemic on Broad Street in central London in 1854. Because of the miasmatic theory's predominance among Italian scientists, the discovery in the same year by Filippo Pacini of the bacillus that caused the disease was completely ignored. It was not until 1876 that Robert Koch proved that the bacterium Bacillus anthracis caused anthrax , which brought a definitive end to miasma theory. The work of John Snow is notable for helping to make the connection between cholera and typhoid epidemics and contaminated water sources, which contributed to the eventual demise of miasma theory. During the cholera epidemic of 1854 , Snow traced high mortality rates among the citizens of Soho to a water pump in Broad Street . Snow convinced the local government to remove the pump handle, which resulted in a marked decrease in cases of cholera in the area. In 1857, Snow submitted a paper to the British Medical Journal which attributed high numbers of cholera cases to water sources that were contaminated with human waste. Snow used statistical data to show that citizens who received their water from upstream sources were considerably less likely to develop cholera than those who received their water from downstream sources. Though his research supported his hypothesis that contaminated water, not foul air, was the source of cholera epidemics, a review committee concluded that Snow's findings were not significant enough to warrant change, and they were summarily dismissed. Additionally, other interests intervened in the process of reform. Many water companies and civic authorities pumped water directly from contaminated sources such as the Thames to public wells, and the idea of changing sources or implementing filtration techniques was an unattractive economic prospect. In the face of such economic interests, reform was slow to be adopted. In 1855, John Snow made a testimony against the Amendment to the "Nuisances Removal and Diseases Prevention Act" that regularized air pollution of some industries. He claimed that: That is possible; but I believe that the poison of the cholera is either swallowed in water, or got directly from some other person in the family, or in the room; I believe it is quite an exception for it to be conveyed in the air; though if the matter gets dry it may be wafted a short distance. In the same year, William Farr , who was then the major supporter of the miasma theory, issued a report to criticize the germ theory. Farr and the Committee wrote that: After careful inquiry, we see no reason to adopt this belief. We do not feel it established that the water was contaminated in the manner alleged; nor is there before us any sufficient evidence to show whether inhabitants of that district, drinking from that well, suffered in proportion more than other inhabitants of the district who drank from other sources. The more formal experiments on the relationship between germ and disease were conducted by Louis Pasteur between 1860 and 1864. He discovered the pathology of the puerperal fever and the pyogenic vibrio in the blood, and suggested using boric acid to kill these microorganisms before and after confinement. By 1866, eight years after the death of John Snow, William Farr publicly acknowledged that the miasma theory on the transmission of cholera was wrong, by his statistical justification on the death rate. Robert Koch is widely known for his work with anthrax , discovering the causative agent of the fatal disease to be Bacillus anthracis . He published the discovery in a booklet as Die Ätiologie der Milzbrand-Krankheit, Begründet auf die Entwicklungsgeschichte des Bacillus Anthracis ( The Etiology of Anthrax Disease, Based on the Developmental History of Bacillus Anthracis ) in 1876 while working in Wöllstein. His publication in 1877 on the structure of anthrax bacterium marked the first photography of a bacterium. He discovered the formation of spores in anthrax bacteria, which could remain dormant under specific conditions. However, under optimal conditions, the spores were activated and caused disease. To determine this causative agent, he dry-fixed bacterial cultures onto glass slides, used dyes to stain the cultures, and observed them through a microscope. His work with anthrax is notable in that he was the first to link a specific microorganism with a specific disease, rejecting the idea of spontaneous generation and supporting the germ theory of disease . The work of John Snow is notable for helping to make the connection between cholera and typhoid epidemics and contaminated water sources, which contributed to the eventual demise of miasma theory. During the cholera epidemic of 1854 , Snow traced high mortality rates among the citizens of Soho to a water pump in Broad Street . Snow convinced the local government to remove the pump handle, which resulted in a marked decrease in cases of cholera in the area. In 1857, Snow submitted a paper to the British Medical Journal which attributed high numbers of cholera cases to water sources that were contaminated with human waste. Snow used statistical data to show that citizens who received their water from upstream sources were considerably less likely to develop cholera than those who received their water from downstream sources. Though his research supported his hypothesis that contaminated water, not foul air, was the source of cholera epidemics, a review committee concluded that Snow's findings were not significant enough to warrant change, and they were summarily dismissed. Additionally, other interests intervened in the process of reform. Many water companies and civic authorities pumped water directly from contaminated sources such as the Thames to public wells, and the idea of changing sources or implementing filtration techniques was an unattractive economic prospect. In the face of such economic interests, reform was slow to be adopted. In 1855, John Snow made a testimony against the Amendment to the "Nuisances Removal and Diseases Prevention Act" that regularized air pollution of some industries. He claimed that: That is possible; but I believe that the poison of the cholera is either swallowed in water, or got directly from some other person in the family, or in the room; I believe it is quite an exception for it to be conveyed in the air; though if the matter gets dry it may be wafted a short distance. In the same year, William Farr , who was then the major supporter of the miasma theory, issued a report to criticize the germ theory. Farr and the Committee wrote that: After careful inquiry, we see no reason to adopt this belief. We do not feel it established that the water was contaminated in the manner alleged; nor is there before us any sufficient evidence to show whether inhabitants of that district, drinking from that well, suffered in proportion more than other inhabitants of the district who drank from other sources. The more formal experiments on the relationship between germ and disease were conducted by Louis Pasteur between 1860 and 1864. He discovered the pathology of the puerperal fever and the pyogenic vibrio in the blood, and suggested using boric acid to kill these microorganisms before and after confinement. By 1866, eight years after the death of John Snow, William Farr publicly acknowledged that the miasma theory on the transmission of cholera was wrong, by his statistical justification on the death rate. Robert Koch is widely known for his work with anthrax , discovering the causative agent of the fatal disease to be Bacillus anthracis . He published the discovery in a booklet as Die Ätiologie der Milzbrand-Krankheit, Begründet auf die Entwicklungsgeschichte des Bacillus Anthracis ( The Etiology of Anthrax Disease, Based on the Developmental History of Bacillus Anthracis ) in 1876 while working in Wöllstein. His publication in 1877 on the structure of anthrax bacterium marked the first photography of a bacterium. He discovered the formation of spores in anthrax bacteria, which could remain dormant under specific conditions. However, under optimal conditions, the spores were activated and caused disease. To determine this causative agent, he dry-fixed bacterial cultures onto glass slides, used dyes to stain the cultures, and observed them through a microscope. His work with anthrax is notable in that he was the first to link a specific microorganism with a specific disease, rejecting the idea of spontaneous generation and supporting the germ theory of disease .

Wiki

Cholera

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

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2020_cholera_outbreak_in_Bengaluru/html

2020 cholera outbreak in Bengaluru

An outbreak of cholera was reported in Bengaluru , Karnataka in March 2020. As of 9 March 2020, there were 17 cases of cholera in Bengaluru. Reports of cholera-like cases were also being reported in large numbers in Bengaluru.The cause of the outbreak is suspected to be a sewage leak in Bengaluru, although the exact focus is yet to be ascertained. Out of the 17 cases recorded, 8 are in the east zone, 7 in the south zone and 2 in the west zone. As of 9 March, there are also 25 suspected cases of cholera in Bengaluru. Most patients were in the age group of 20-40, belonging to the IT corridor of Bengaluru. The Bengaluru civic body evicted street food vendors and footpath sellers to ensure the city's cleanliness and to prevent the further transmission of the disease. The samples of water taken from various parts of the city were sent for testing to Public Health Institute on the suspicion that sewage is being mixed with drinking water. The cholera outbreak is amidst the concerns of the spread of coronavirus in Karnataka . Water supply was stopped to some of the areas where the cases were reported. The Chief Health Officer of Bengaluru said that cholera help desks have been set up in urban primary health centres of the city.

Wiki

Cholera

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

Cholera belt

The cholera belt was a flat strip of (usually red) flannel or knitted wool, about six feet long and six inches wide, that was wrapped around the bare abdomen. The item was standard army issue, and was purported to prevent the wearer from contracting cholera , dysentery , and other ailments believed to be caused by chilling of the abdomen. The belts use continued decades after the causative link between pathogen-contaminated drinking water and cholera was established. Attempts to prevent illness by wearing flannel body wraps date to the early 1700s. In 1707 Jeremiah Wainewright wrote "'I was perswaded'(sic) ... to wear Flannel next to my Skin some ten Years ago for a severe Cough ... I received some advantage'", and in 1726 author Richard Towne wrote, "'those who are subject to habitual Looseness may receive great Benefit by wearing Flannel and keeping their Bodies warm'". By 1799 the British army promoted a "flannel bandage to the whole abdomen," with surgeon Robert Jackson in 1817 recommending "the application of 'flannel over the abdomen, adding such pressure to it by a flannel roller'" to prevent dysentery, and James Annesley writing in 1828 that "'use of a thick flannel banyan and cummerband during the Monsoon will ... exert considerable influence in preventing bowel complaints'". According to historian E.T. Renbourn, flannel waistcoats and belts were commonly worn by British soldiers before the 1830s but as cholera epidemics spread from 1817 to the 1830s, fear spread leading to reports in the Cholera Gazette that soldiers should wear flannel to prevent cholera, possibly originating in the Polish-Russian War of 1830-31 though a "cholera belt" was not mentioned. Renbourn writes that although the phrase "cholera belt" was not being specifically mentioned in print, it was "being used fairly widely by the populace in general". It was not until 1848 when, Instructions to Army Medical Officers for their Guidance on the Appearance of the Spasmodic Cholera included the suggestion that every soldier should be provided two "cholera belts". In 1849 an anonymous author published the pamphlet "What has Cholera done in London?" advising "readers to wear a folded flannel belt around the belly ... recommended by the Board of Health'". J. McGrigor Croft, M.D. writing in the Westminster, England Marylebone Mercury in 1866 that he was the inventor of the cholera belt. Croft states that he did this to "aid the poor" and then describes how to make the belt out of ordinary flannel in the hopes that anyone will be able to make their own. He states that two medical doctors of his acquaintance vouch for the invention. He calls it an "abdominal respirator; it permits the heated perspiration of the body to pass off without any chance of chill ... without any inconvenience such as found in the old cholera belt". Croft goes on to say that he has declined the patent and gives it to the public freely. Surgeon in the Bengal Army, Andrew Duncan in 1888 wrote that "'Cholera belts must be stringently insisted on ... and there should be periodic inspection - and without warning - to see that men are wearing them'". In 1898, The San Francisco Call reported that the belt is a "good thing for the troops" quoting advice from a Major Edward Field "that no soldier should think of going to Manila without a cholera belt". And although it is impossible to take everything a soldier would need in the tropics, the cholera belt holds the highest place in the emergency list". In 1914, donations by the tiny village of Middlemarch , New Zealand of items such as tobacco, shirts and tinned fruit for soldiers going to fight in World War I , included "26 cholera belts". The idea of abdominal chilling as a factor in illness was brought up as late as 1947 although it was rejoined by those who pointed out that the idea was not based on experimental evidence. Renbourn sums up the history of cholera belts as an interest in wearing them fluctuated whether an outbreak was happening nearby or not. The argument seems to be that it "prevented suppression of 'perspiration' and the consequent flow of blocked excretions to the bowel". In 1946, L. E. Napier wrote in Principles and Practice of Tropical Medicine that "The flannel cholera belt, whose powers of cholera prevention were of course mythical ... has fortunately gone out of fashion".

Wiki

Cholera

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

John Snow

John Snow (15 March 1813 – 16 June 1858 ) was an English physician and a leader in the development of anaesthesia and medical hygiene . He is considered one of the founders of modern epidemiology and early germ theory , in part because of his work in tracing the source of a cholera outbreak in London's Soho , which he identified as a particular public water pump. Snow's findings inspired fundamental changes in the water and waste systems of London , which led to similar changes in other cities, and a significant improvement in general public health around the world. Snow was born on 15 March 1813 in York , England, the first of nine children born to William and Frances Snow in their North Street home, and was baptised at All Saints' Church, North Street, York . His father was a labourer who worked at a local coal yard, by the Ouse, constantly replenished from the Yorkshire coalfield by barges, but later was a farmer in a small village to the north of York. The neighbourhood was one of the poorest in the city, and was frequently in danger of flooding because of its proximity to the River Ouse . Growing up, Snow experienced unsanitary conditions and contamination in his hometown. Most of the streets were unsanitary and the river was contaminated by runoff water from market squares, cemeteries and sewage. From a young age, Snow demonstrated an aptitude for mathematics. In 1827, when he was 14, he obtained a medical apprenticeship with William Hardcastle in the area of Newcastle-upon-Tyne . In 1832, during his time as a surgeon-apothecary apprentice, he encountered a cholera epidemic for the first time in Killingworth , a coal-mining village. Snow treated many victims of the disease and thus gained experience. Eventually he adjusted to teetotalism and led a life characterized by abstinence, signing an abstinence pledge in 1835. Snow was also a vegetarian and tried to only drink distilled water that was "pure". Between 1832 and 1835 Snow worked as an assistant to a colliery surgeon, first in Burnopfield , County Durham, and then in Pateley Bridge , West Riding of Yorkshire . In October 1836 he enrolled at the Hunterian school of medicine on Great Windmill Street , London. In the 1830s, Snow's colleague at the Newcastle Infirmary was surgeon Thomas Michael Greenhow . The surgeons worked together conducting research on England's cholera epidemics, both continuing to do so for many years. In 1837, Snow began working at the Westminster Hospital . Admitted as a member of the Royal College of Surgeons of England on 2 May 1838, he graduated from the University of London in December 1844 and was admitted to the Royal College of Physicians in 1850. Snow was a founding member of the Epidemiological Society of London which was formed in May 1850 in response to the cholera outbreak of 1849. By 1856, Snow and Greenhow's nephew, Dr. E.H. Greenhow were some of a handful of esteemed medical men of the society who held discussions on this "dreadful scourge, the cholera ". After finishing his medical studies in the University of London , he earned his MD in 1844. Snow set up his practice at 54 Frith Street in Soho as a surgeon and general practitioner. John Snow contributed to a wide range of medical concerns including anaesthesiology . He was a member of the Westminster Medical Society , an organisation dedicated to clinical and scientific demonstrations. Snow gained prestige and recognition all the while being able to experiment and pursue many of his scientific ideas. He was a speaker multiple times at the society's meetings and he also wrote and published articles. He was especially interested in patients with respiratory diseases and tested his hypothesis through animal studies. In 1841, he wrote, On Asphyxiation, and on the Resuscitation of Still-Born Children , which is an article that discusses his discoveries on the physiology of neonatal respiration, oxygen consumption and the effects of body temperature change. In 1857, Snow made an early and often overlooked contribution to epidemiology in a pamphlet, On the adulteration of bread as a cause of rickets . Snow's interest in anaesthesia and breathing was evident from 1841 and beginning in 1843, he experimented with ether to see its effects on respiration. Only a year after ether was introduced to Britain, in 1847, he published a short work titled, On the Inhalation of the Vapor of Ether, which served as a guide for its use. At the same time, he worked on various papers that reported his clinical experience with anaesthesia, noting reactions, procedures and experiments. Within two years of ether being introduced, Snow was the most accomplished anaesthetist in Britain. London's principal surgeons suddenly wanted his assistance. As well as ether, John Snow studied chloroform , which was introduced in 1847 by James Young Simpson , a Scottish obstetrician. He realised that chloroform was much more potent and required more attention and precision when administering it. Snow first realised this with Hannah Greener, a 15-year-old patient who died on 28 January 1848 after a surgical procedure that required the cutting of her toenail. She was administered chloroform by covering her face with a cloth dipped in the substance. However, she quickly lost pulse and died. After investigating her death and a couple of deaths that followed, he realized that chloroform had to be administered carefully and published his findings in a letter to The Lancet . John Snow was one of the first physicians to study and calculate dosages for the use of ether and chloroform as surgical anaesthetics , allowing patients to undergo surgical and obstetric procedures without the distress and pain they would otherwise experience. He designed the apparatus to safely administer ether to the patients and also designed a mask to administer chloroform. Snow published an article on ether in 1847 entitled On the Inhalation of the Vapor of Ether . A longer version entitled On Chloroform and Other Anaesthetics and Their Action and Administration was published posthumously in 1858. Although he thoroughly worked with ether as an anaesthetic, he never attempted to patent it; instead, he continued to work and publish written works on his observations and research. Snow's work and findings were related to both anaesthesia and the practice of childbirth. His experience with obstetric patients was extensive and used different substances including ether, amylene and chloroform to treat his patients. However, chloroform was the easiest drug to administer. He treated 77 obstetric patients with chloroform. He would apply the chloroform at the second stage of labour and controlled the amount without completely putting the patients to sleep. Once the patient was delivering the baby, they would only feel the first half of the contraction and be on the border of unconsciousness, but not fully there. Regarding administration of the anaesthetic, Snow believed that it would be safer if another person that was not the surgeon applied it. The use of chloroform as an anaesthetic for childbirth was seen as unethical by many physicians and even the Church of England . However, on 7 April 1853, Queen Victoria asked John Snow to administer chloroform during the delivery of her eighth child, Leopold . He then repeated the procedure for the delivery of her daughter Beatrice in 1857. This led to wider acceptance of obstetrical anaesthesia. Snow was a skeptic of the then-dominant miasma theory that stated that diseases such as cholera and bubonic plague were caused by pollution or a noxious form of "bad air". The germ theory of disease had not yet been developed, so Snow did not understand the mechanism by which the disease was transmitted. His observation of the evidence led him to discount the theory of foul air. He first published his theory in an 1849 essay, On the Mode of Communication of Cholera , followed by a more detailed treatise in 1855 incorporating the results of his investigation of the role of the water supply in the Soho epidemic of 1854. By talking to local residents (with the help of Henry Whitehead ), he identified the source of the outbreak as the public water pump on Broad Street (now Broadwick Street ). Although Snow's chemical and microscope examination of a water sample from the Broad Street pump did not conclusively prove its danger, his studies of the pattern of the disease were convincing enough to persuade the local council to disable the well pump by removing its handle ( force rod ). This action has been commonly credited as ending the outbreak, but Snow observed that the epidemic may have already been in rapid decline: There is no doubt that the mortality was much diminished, as I said before, by the flight of the population, which commenced soon after the outbreak; but the attacks had so far diminished before the use of the water was stopped, that it is impossible to decide whether the well still contained the cholera poison in an active state, or whether, from some cause, the water had become free from it. : 51–52 Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases. He showed that homes supplied by the Southwark and Vauxhall Waterworks Company , which was taking water from sewage-polluted sections of the Thames , had a cholera rate fourteen times that of those supplied by Lambeth Waterworks Company , which obtained water from the upriver, cleaner Seething Wells . Snow's study was a major event in the history of public health and geography. It is regarded as the founding event of the science of epidemiology . [ citation needed ] Snow wrote: On proceeding to the spot, I found that nearly all the deaths had taken place within a short distance of the [Broad Street] pump. There were only ten deaths in houses situated decidedly nearer to another street-pump. In five of these cases the families of the deceased persons informed me that they always sent to the pump in Broad Street, as they preferred the water to that of the pumps which were nearer. In three other cases, the deceased were children who went to school near the pump in Broad Street... With regard to the deaths occurring in the locality belonging to the pump, there were 61 instances in which I was informed that the deceased persons used to drink the pump water from Broad Street, either constantly or occasionally... The result of the inquiry, then, is, that there has been no particular outbreak or prevalence of cholera in this part of London except among the persons who were in the habit of drinking the water of the above-mentioned pump well. I had an interview with the Board of Guardians of St James's parish, on the evening of the 7th inst [7 September], and represented the above circumstances to them. In consequence of what I said, the handle of the pump was removed on the following day. Researchers later discovered that this public well had been dug only 3 feet (0.9 m) from an old cesspit , which had begun to leak faecal bacteria. The cloth nappy of a baby, who had contracted cholera from another source, had been washed into this cesspit. Its opening was originally under a nearby house, which had been rebuilt farther away after a fire. The city had widened the street and the cesspit was lost. It was common at the time to have a cesspit under most homes. Most families tried to have their raw sewage collected and dumped in the Thames to prevent their cesspit from filling faster than the sewage could decompose into the soil. Thomas Shapter had conducted similar studies and used a point-based map for the study of cholera in Exeter , seven years before John Snow, although this did not identify the water supply problem that was later held responsible. After the cholera epidemic had subsided, government officials replaced the Broad Street pump handle. They had responded only to the urgent threat posed to the population, and afterward they rejected Snow's theory. To accept his proposal would have meant indirectly accepting the fecal-oral route of disease transmission, which was too unpleasant for most of the public to contemplate. It was not until 1866 that William Farr , one of Snow's chief opponents, realised the validity of his diagnosis when investigating another outbreak of cholera at Bromley by Bow and issued immediate orders that unboiled water was not to be drunk. Farr denied Snow's explanation of how exactly the contaminated water spread cholera, although he did accept that water had a role in the spread of the illness. In fact, some of the statistical data that Farr collected helped promote John Snow's views. Public health officials recognise the political struggles in which reformers have often become entangled. During the annual Pumphandle Lecture in England, members of the John Snow Society remove and replace a pump handle to symbolise the continuing challenges for advances in public health. Snow's interest in anaesthesia and breathing was evident from 1841 and beginning in 1843, he experimented with ether to see its effects on respiration. Only a year after ether was introduced to Britain, in 1847, he published a short work titled, On the Inhalation of the Vapor of Ether, which served as a guide for its use. At the same time, he worked on various papers that reported his clinical experience with anaesthesia, noting reactions, procedures and experiments. Within two years of ether being introduced, Snow was the most accomplished anaesthetist in Britain. London's principal surgeons suddenly wanted his assistance. As well as ether, John Snow studied chloroform , which was introduced in 1847 by James Young Simpson , a Scottish obstetrician. He realised that chloroform was much more potent and required more attention and precision when administering it. Snow first realised this with Hannah Greener, a 15-year-old patient who died on 28 January 1848 after a surgical procedure that required the cutting of her toenail. She was administered chloroform by covering her face with a cloth dipped in the substance. However, she quickly lost pulse and died. After investigating her death and a couple of deaths that followed, he realized that chloroform had to be administered carefully and published his findings in a letter to The Lancet . John Snow was one of the first physicians to study and calculate dosages for the use of ether and chloroform as surgical anaesthetics , allowing patients to undergo surgical and obstetric procedures without the distress and pain they would otherwise experience. He designed the apparatus to safely administer ether to the patients and also designed a mask to administer chloroform. Snow published an article on ether in 1847 entitled On the Inhalation of the Vapor of Ether . A longer version entitled On Chloroform and Other Anaesthetics and Their Action and Administration was published posthumously in 1858. Although he thoroughly worked with ether as an anaesthetic, he never attempted to patent it; instead, he continued to work and publish written works on his observations and research.Snow's work and findings were related to both anaesthesia and the practice of childbirth. His experience with obstetric patients was extensive and used different substances including ether, amylene and chloroform to treat his patients. However, chloroform was the easiest drug to administer. He treated 77 obstetric patients with chloroform. He would apply the chloroform at the second stage of labour and controlled the amount without completely putting the patients to sleep. Once the patient was delivering the baby, they would only feel the first half of the contraction and be on the border of unconsciousness, but not fully there. Regarding administration of the anaesthetic, Snow believed that it would be safer if another person that was not the surgeon applied it. The use of chloroform as an anaesthetic for childbirth was seen as unethical by many physicians and even the Church of England . However, on 7 April 1853, Queen Victoria asked John Snow to administer chloroform during the delivery of her eighth child, Leopold . He then repeated the procedure for the delivery of her daughter Beatrice in 1857. This led to wider acceptance of obstetrical anaesthesia. Snow was a skeptic of the then-dominant miasma theory that stated that diseases such as cholera and bubonic plague were caused by pollution or a noxious form of "bad air". The germ theory of disease had not yet been developed, so Snow did not understand the mechanism by which the disease was transmitted. His observation of the evidence led him to discount the theory of foul air. He first published his theory in an 1849 essay, On the Mode of Communication of Cholera , followed by a more detailed treatise in 1855 incorporating the results of his investigation of the role of the water supply in the Soho epidemic of 1854. By talking to local residents (with the help of Henry Whitehead ), he identified the source of the outbreak as the public water pump on Broad Street (now Broadwick Street ). Although Snow's chemical and microscope examination of a water sample from the Broad Street pump did not conclusively prove its danger, his studies of the pattern of the disease were convincing enough to persuade the local council to disable the well pump by removing its handle ( force rod ). This action has been commonly credited as ending the outbreak, but Snow observed that the epidemic may have already been in rapid decline: There is no doubt that the mortality was much diminished, as I said before, by the flight of the population, which commenced soon after the outbreak; but the attacks had so far diminished before the use of the water was stopped, that it is impossible to decide whether the well still contained the cholera poison in an active state, or whether, from some cause, the water had become free from it. : 51–52 Snow later used a dot map to illustrate the cluster of cholera cases around the pump. He also used statistics to illustrate the connection between the quality of the water source and cholera cases. He showed that homes supplied by the Southwark and Vauxhall Waterworks Company , which was taking water from sewage-polluted sections of the Thames , had a cholera rate fourteen times that of those supplied by Lambeth Waterworks Company , which obtained water from the upriver, cleaner Seething Wells . Snow's study was a major event in the history of public health and geography. It is regarded as the founding event of the science of epidemiology . [ citation needed ] Snow wrote: On proceeding to the spot, I found that nearly all the deaths had taken place within a short distance of the [Broad Street] pump. There were only ten deaths in houses situated decidedly nearer to another street-pump. In five of these cases the families of the deceased persons informed me that they always sent to the pump in Broad Street, as they preferred the water to that of the pumps which were nearer. In three other cases, the deceased were children who went to school near the pump in Broad Street... With regard to the deaths occurring in the locality belonging to the pump, there were 61 instances in which I was informed that the deceased persons used to drink the pump water from Broad Street, either constantly or occasionally... The result of the inquiry, then, is, that there has been no particular outbreak or prevalence of cholera in this part of London except among the persons who were in the habit of drinking the water of the above-mentioned pump well. I had an interview with the Board of Guardians of St James's parish, on the evening of the 7th inst [7 September], and represented the above circumstances to them. In consequence of what I said, the handle of the pump was removed on the following day. Researchers later discovered that this public well had been dug only 3 feet (0.9 m) from an old cesspit , which had begun to leak faecal bacteria. The cloth nappy of a baby, who had contracted cholera from another source, had been washed into this cesspit. Its opening was originally under a nearby house, which had been rebuilt farther away after a fire. The city had widened the street and the cesspit was lost. It was common at the time to have a cesspit under most homes. Most families tried to have their raw sewage collected and dumped in the Thames to prevent their cesspit from filling faster than the sewage could decompose into the soil. Thomas Shapter had conducted similar studies and used a point-based map for the study of cholera in Exeter , seven years before John Snow, although this did not identify the water supply problem that was later held responsible. After the cholera epidemic had subsided, government officials replaced the Broad Street pump handle. They had responded only to the urgent threat posed to the population, and afterward they rejected Snow's theory. To accept his proposal would have meant indirectly accepting the fecal-oral route of disease transmission, which was too unpleasant for most of the public to contemplate. It was not until 1866 that William Farr , one of Snow's chief opponents, realised the validity of his diagnosis when investigating another outbreak of cholera at Bromley by Bow and issued immediate orders that unboiled water was not to be drunk. Farr denied Snow's explanation of how exactly the contaminated water spread cholera, although he did accept that water had a role in the spread of the illness. In fact, some of the statistical data that Farr collected helped promote John Snow's views. Public health officials recognise the political struggles in which reformers have often become entangled. During the annual Pumphandle Lecture in England, members of the John Snow Society remove and replace a pump handle to symbolise the continuing challenges for advances in public health. After the cholera epidemic had subsided, government officials replaced the Broad Street pump handle. They had responded only to the urgent threat posed to the population, and afterward they rejected Snow's theory. To accept his proposal would have meant indirectly accepting the fecal-oral route of disease transmission, which was too unpleasant for most of the public to contemplate. It was not until 1866 that William Farr , one of Snow's chief opponents, realised the validity of his diagnosis when investigating another outbreak of cholera at Bromley by Bow and issued immediate orders that unboiled water was not to be drunk. Farr denied Snow's explanation of how exactly the contaminated water spread cholera, although he did accept that water had a role in the spread of the illness. In fact, some of the statistical data that Farr collected helped promote John Snow's views. Public health officials recognise the political struggles in which reformers have often become entangled. During the annual Pumphandle Lecture in England, members of the John Snow Society remove and replace a pump handle to symbolise the continuing challenges for advances in public health. Snow was known to swim as a hobby for exercise. He became a vegetarian at the age of 17 and was a teetotaller . He embraced a lacto-ovo vegetarian diet by supplementing his vegetables with dairy products and eggs for eight years. Whilst in his thirties he became a vegan . His health deteriorated and he suffered a renal disorder which he attributed to his vegan diet so he took up meat-eating and drinking wine. He continued drinking pure water (via boiling) throughout his adult life. He never married. In 1830, Snow became a member of the temperance movement . In 1845, he became a member of York Temperance Society. After his health declined it was only about 1845 that he consumed a little wine to aid digestion. Snow lived at 18 Sackville Street , London, from 1852 to his death in 1858. Snow suffered a stroke while working in his London office on 10 June 1858. He was 45 years old at the time. He never recovered, dying six days later on 16 June 1858. He was buried in Brompton Cemetery . It has been speculated that his premature death may have been related to his frequent exposure and experimentation with anesthetic gases, which is now known to have numerous adverse health effects. Snow administered and experimented with ether, chloroform, ethyl nitrate, carbon disulfide, benzene, bromoform, ethyl bromide and dichloroethane during his lifetime.

Wiki

Cholera

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

Native American disease and epidemics

Although a variety of infectious diseases existed in the Americas in pre-Columbian times, the limited size of the populations, smaller number of domesticated animals with zoonotic diseases , and limited interactions between those populations (as compared to areas of Eurasia and Africa) hampered the transmission of communicable diseases. One notable infectious disease that may be of American origin is syphilis . Aside from that, most of the major infectious diseases known today originated in the Old World (Africa and Eurasia). The American era of limited infectious disease ended with the arrival of Europeans in the Americas and the Columbian exchange of microorganisms, including those that cause human diseases. Eurasian infections and epidemics had major effects on Native American life in the colonial period and nineteenth century, especially. Eurasia was a crossroads among many distant, different peoples separated by hundreds, if not thousands, of miles. But repeated warfare by invading populations spread infectious disease throughout the continent, as did trade, including the Silk Road . For more than 1,000 years travelers brought goods and infectious diseases from the East, where some of the latter had jumped from animals to humans . As a result of chronic exposure, many infections became endemic within their societies over time, so that surviving Europeans gradually developed some acquired immunity, although they were still vulnerable to pandemics and epidemics. Europeans carried such endemic diseases when they migrated and explored the New World. Native Americans often contracted infectious disease through trading and exploration contacts with Europeans, and these were transmitted far from the sources and colonial settlements, through exclusively Native American trading transactions. Warfare and enslavement also contributed to disease transmission. Because their populations had not been previously exposed to most of these infectious diseases, the indigenous people rarely had individual or population acquired immunity and consequently suffered very high mortality. The numerous deaths disrupted Native American societies. This phenomenon is known as the virgin soil effect . The arrival and settlement of Europeans in the Americas resulted in what is known as the Columbian exchange . During this period European settlers brought many different technologies, animals, plants, and lifestyles with them, some of which benefited the indigenous peoples. Europeans also took plants and goods back to the Old World. Potatoes and tomatoes from the Americas became integral to European and Asian cuisines, for instance. But Europeans also unintentionally brought new infectious diseases , including smallpox , bubonic plague , chickenpox , cholera , the common cold , diphtheria , influenza , malaria , measles , scarlet fever , sexually transmitted diseases (with the possible exception of syphilis ), typhoid , typhus , tuberculosis (although a form of this infection existed in South America prior to contact), and pertussis . Each of these resulted in sweeping epidemics among Native Americans, who had disability, illness, and a high mortality rate . The Europeans infected with such diseases typically carried them in a dormant state , were actively infected but asymptomatic , or had only mild symptoms, because Europe had been subject for centuries to a selective process by these diseases. The explorers and colonists often unknowingly passed the diseases to natives. The introduction of African slaves and the use of commercial trade routes contributed to the spread of disease. The infections brought by Europeans are not easily tracked, since there were numerous outbreaks and all were not equally recorded. 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 many epidemics overlapped with multiple infections striking the same population at once, therefore it is often impossible to know the exact causes of mortality (although ancient DNA studies can often determine the presence of certain microbes). Smallpox was the disease brought by Europeans that was most destructive 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. Native Americans initially believed that illness primarily resulted from being out of balance, in relation to their religious beliefs. Typically, Native Americans held that disease was caused by either a lack of magical protection, the intrusion of an object into the body by means of sorcery , or the absence of the free soul from the body. Disease was understood to enter the body as a natural occurrence if a person was not protected by spirits, or less commonly as a result of malign human or supernatural intervention. For example, Cherokee spiritual beliefs attribute disease to revenge imposed by animals for killing them. In some cases, disease was seen as a punishment for disregarding tribal traditions or disobeying tribal rituals. Spiritual powers were called on to cure diseases through the practice of shamanism . Most Native American tribes also used a wide variety of medicinal plants and other substances in the treatment of disease. Smallpox was lethal to many Native Americans, resulting in sweeping epidemics and repeatedly affecting the same tribes. After its introduction to Mexico in 1519, the disease spread across South America, devastating indigenous populations in what are now Colombia, Peru and Chile during the sixteenth century. The disease was slow to spread northward due to the sparse population of the northern Mexico desert region. It was introduced to eastern North America separately by colonists arriving in 1633 to Plymouth, Massachusetts , and local Native American communities were soon struck by the virus. It reached the Mohawk nation in 1634, the Lake Ontario area in 1636, and the lands of other Iroquois tribes by 1679. Between 1613 and 1690 the Iroquois tribes living in Quebec suffered twenty-four epidemics, almost all of them caused by smallpox. By 1698 the virus had crossed the Mississippi, causing an epidemic that nearly obliterated the Quapaw Indians of Arkansas. The disease was often spread during war. John McCullough, a Delaware captive since July 1756, who was then 15 years old, wrote that the Lenape people, under the leadership of Shamokin Daniel, "committed several depredations along the Juniata ; it happened to be at a time when the smallpox was in the settlement where they were murdering, the consequence was, a number of them got infected, and some died before they got home, others shortly after; those who took it after their return, were immediately moved out of the town, and put under the care of one who had the disease before." By the mid-eighteenth century the disease was affecting populations severely enough to interrupt trade and negotiations. Thomas Hutchins , in his August 1762 journal entry while at Ohio's Fort Miami , named for the Mineamie people, wrote: The 20th, The above Indians met, and the Ouiatanon Chief spoke in behalf of his and the Kickaupoo Nations as follows: "Brother, We are very thankful to Sir William Johnson for sending you to enquire into the State of the Indians. We assure you we are Rendered very miserable at Present on Account of a Severe Sickness that has seiz'd almost all our People, many of which have died lately, and many more likely to Die..." The 30th, Set out for the Lower Shawneese Town and arriv'd 8th of September in the afternoon. I could not have a meeting with the Shawneese the 12th, as their People were Sick and Dying every day. On June 24, 1763, during the siege of Fort Pitt , as recorded in his journal by fur trader and militia captain William Trent , dignitaries from the Delaware tribe met with British officials at the fort, warned them of "great numbers of Indians" coming to attack the fort, and pleaded with them to leave the fort while there was still time. The commander of the fort, Simeon Ecuyear, refused to abandon the fort. Instead, Ecuyear gave as gifts two blankets, one silk handkerchief and one piece of linen- all infected with smallpox from the fort infirmary- to the two Delaware emissaries Turtleheart and Mamaltee, allegedly in the hope of spreading the deadly disease to nearby tribes, as attested in Trent's journal. The dignitaries were met again later and they seemingly hadn't contracted smallpox. A relatively small outbreak of smallpox had begun spreading earlier that spring, with a hundred dying from it among Native American tribes in the Ohio Valley and Great Lakes area through 1763 and 1764. The effectiveness of the biological warfare itself remains unknown, and the method used is inefficient compared to airborne transmission . 21st-century scientists such as V. Barras and G. Greub have examined such reports. They say that smallpox is spread by respiratory droplets in personal interaction, not by contact with fomites , such objects as were described by Trent. The results of such attempts to spread the disease through objects are difficult to differentiate from naturally occurring epidemics. Gershom Hicks, held captive by the Ohio Country Shawnee and Delaware between May 1763 and April 1764, reported to Captain William Grant of the 42nd Regiment "that the Small pox has been very general & raging amongst the Indians since last spring and that 30 or 40 Mingoes , as many Delawares and some Shawneese Died all of the Small pox since that time, that it still continues amongst them". In 1832 President Andrew Jackson signed Congressional authorization and funding to set up a smallpox vaccination program for Indian tribes. The goal was to eliminate the deadly threat of smallpox to a population with little or no immunity, and at the same time exhibit the benefits of cooperation with the government. In practice there were severe obstacles. The tribal medicine men launched a strong opposition, warning of white trickery and offering an alternative explanation and system of cure. Some taught that the affliction could best be cured by a sweat bath followed by a rapid plunge into cold water. Furthermore the vaccines often lost their potency when transported and stored over long distances with primitive storage facilities. It was too little and too late to avoid the great smallpox epidemic of 1837 to 1840 that swept across North America west of the Mississippi, all the way to Canada and Alaska. Deaths have been estimated in the range of 100,000 to 300,000, with entire tribes wiped out. Over 90 percent of the Mandans died. In the mid to late nineteenth century, at a time of increasing European-American travel and settlement in the West, at least four different epidemics broke out among the Plains tribes between 1837 and 1870. When the Plains tribes began to learn of the "white man's diseases", many intentionally avoided contact with them and their trade goods. But the lure of trade goods such as metal pots, skillets, and knives sometimes proved too strong. The Indians traded with the white newcomers anyway and inadvertently spread disease to their villages. In the late 19th century, the Lakota Indians of the Plains called the disease the "rotting face sickness". The 1862 Pacific Northwest smallpox epidemic , which was brought from San Francisco to Victoria , devastated the indigenous peoples of the Pacific Northwest Coast , with a death rate of over 50% for the entire coast from Puget Sound to Southeast Alaska . In some areas the native population fell by as much as 90%. Some historians have described the epidemic as a deliberate genocide because the Colony of Vancouver Island and the Colony of British Columbia could have prevented the epidemic but chose not to, and in some ways facilitated it. Many Native American tribes suffered high mortality and depopulation, averaging 25–50% of the tribes' members dead from disease. Additionally, some smaller tribes neared extinction after facing a severely destructive spread of disease. A specific example was what followed Cortés ' invasion of Mexico . Before his arrival, the Mexican population is estimated to have been around 25 to 30 million. Fifty years later, the Mexican population was reduced to 3 million, mainly by infectious disease. A 2018 study by Koch, Brierley, Maslin and Lewis concluded that an estimated "55 million indigenous people died following the European conquest of the Americas beginning in 1492." Estimates for the entire number of human lives lost during the Cocoliztli epidemics in New Spain have ranged from 5 to 15 million people, making it one of the most deadly disease outbreaks of all time. By 1700, fewer than 5,000 Native Americans remained in the southeastern coastal region of the United States. In Florida alone, an estimated 700,000 Native Americans lived there in 1520, but by 1700 the number was around 2,000. Some 21st-century climate scientists have suggested that a severe reduction of the indigenous population in the Americas and the accompanying reduction in cultivated lands during the 16th, 17th and 18th centuries may have contributed to a global cooling event known as the Little Ice Age . The loss of the population was so high that it was partially responsible for the myth of the Americas as "virgin wilderness". By the time significant European colonization was underway, native populations had already been reduced by 90%. This resulted in settlements vanishing and cultivated fields being abandoned. Since forests were recovering, the colonists had an impression of a land that was an untamed wilderness. Disease had both direct and indirect effects on deaths. High mortality meant that there were fewer people to plant crops, hunt game, and otherwise support the group. Loss of cultural knowledge transfer also affected the community as vital agricultural and food-gathering skills were not passed on to survivors. Missing the right time to hunt or plant crops affected the food supply, thus further weakening the community and making it more vulnerable to the next epidemic. Communities under such crisis were often unable to care for people who were disabled, elderly, or young. In summer 1639, a smallpox epidemic struck the Huron natives in the St. Lawrence and Great Lakes regions. The disease had reached the Huron tribes through French colonial traders from Québec who remained in the region throughout the winter. When the epidemic was over, the Huron population had been reduced to roughly 9,000 people, about half of what it had been before 1634. The Iroquois people, generally south of the Great Lakes, faced similar losses after encounters with French, Dutch and English colonists. During the 1770s, smallpox killed at least 30% (tens of thousands) of the Northwestern Native Americans. The smallpox epidemic of 1780–1782 brought devastation and drastic depopulation among the Plains Indians . By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. The Commissioner of Indian Affairs in 1839 reported on the casualties of the 1837 Great Plains smallpox epidemic : "No attempt has been made to count the victims, nor is it possible to reckon them in any of these tribes with accuracy; it is believed that if [the number 17,200 for the upper Missouri River Indians] was doubled, the aggregate would not be too large for those who have fallen east of the Rocky Mountains ." Historian David Stannard asserts that by "focusing almost entirely on disease ... contemporary authors increasingly have created the impression that the eradication of those tens of millions of people was inadvertent—a sad, but both inevitable and 'unintended consequence' of human migration and progress." He says that their destruction "was neither inadvertent nor inevitable", but the result of microbial pestilence and purposeful genocide working in tandem. Historian Andrés Reséndez says that evidence suggests "among these human factors, slavery has emerged as a major killer" of the indigenous populations of the Caribbean between 1492 and 1550, rather than diseases such as smallpox, influenza and malaria. Smallpox was lethal to many Native Americans, resulting in sweeping epidemics and repeatedly affecting the same tribes. After its introduction to Mexico in 1519, the disease spread across South America, devastating indigenous populations in what are now Colombia, Peru and Chile during the sixteenth century. The disease was slow to spread northward due to the sparse population of the northern Mexico desert region. It was introduced to eastern North America separately by colonists arriving in 1633 to Plymouth, Massachusetts , and local Native American communities were soon struck by the virus. It reached the Mohawk nation in 1634, the Lake Ontario area in 1636, and the lands of other Iroquois tribes by 1679. Between 1613 and 1690 the Iroquois tribes living in Quebec suffered twenty-four epidemics, almost all of them caused by smallpox. By 1698 the virus had crossed the Mississippi, causing an epidemic that nearly obliterated the Quapaw Indians of Arkansas. The disease was often spread during war. John McCullough, a Delaware captive since July 1756, who was then 15 years old, wrote that the Lenape people, under the leadership of Shamokin Daniel, "committed several depredations along the Juniata ; it happened to be at a time when the smallpox was in the settlement where they were murdering, the consequence was, a number of them got infected, and some died before they got home, others shortly after; those who took it after their return, were immediately moved out of the town, and put under the care of one who had the disease before." By the mid-eighteenth century the disease was affecting populations severely enough to interrupt trade and negotiations. Thomas Hutchins , in his August 1762 journal entry while at Ohio's Fort Miami , named for the Mineamie people, wrote: The 20th, The above Indians met, and the Ouiatanon Chief spoke in behalf of his and the Kickaupoo Nations as follows: "Brother, We are very thankful to Sir William Johnson for sending you to enquire into the State of the Indians. We assure you we are Rendered very miserable at Present on Account of a Severe Sickness that has seiz'd almost all our People, many of which have died lately, and many more likely to Die..." The 30th, Set out for the Lower Shawneese Town and arriv'd 8th of September in the afternoon. I could not have a meeting with the Shawneese the 12th, as their People were Sick and Dying every day. On June 24, 1763, during the siege of Fort Pitt , as recorded in his journal by fur trader and militia captain William Trent , dignitaries from the Delaware tribe met with British officials at the fort, warned them of "great numbers of Indians" coming to attack the fort, and pleaded with them to leave the fort while there was still time. The commander of the fort, Simeon Ecuyear, refused to abandon the fort. Instead, Ecuyear gave as gifts two blankets, one silk handkerchief and one piece of linen- all infected with smallpox from the fort infirmary- to the two Delaware emissaries Turtleheart and Mamaltee, allegedly in the hope of spreading the deadly disease to nearby tribes, as attested in Trent's journal. The dignitaries were met again later and they seemingly hadn't contracted smallpox. A relatively small outbreak of smallpox had begun spreading earlier that spring, with a hundred dying from it among Native American tribes in the Ohio Valley and Great Lakes area through 1763 and 1764. The effectiveness of the biological warfare itself remains unknown, and the method used is inefficient compared to airborne transmission . 21st-century scientists such as V. Barras and G. Greub have examined such reports. They say that smallpox is spread by respiratory droplets in personal interaction, not by contact with fomites , such objects as were described by Trent. The results of such attempts to spread the disease through objects are difficult to differentiate from naturally occurring epidemics. Gershom Hicks, held captive by the Ohio Country Shawnee and Delaware between May 1763 and April 1764, reported to Captain William Grant of the 42nd Regiment "that the Small pox has been very general & raging amongst the Indians since last spring and that 30 or 40 Mingoes , as many Delawares and some Shawneese Died all of the Small pox since that time, that it still continues amongst them". In 1832 President Andrew Jackson signed Congressional authorization and funding to set up a smallpox vaccination program for Indian tribes. The goal was to eliminate the deadly threat of smallpox to a population with little or no immunity, and at the same time exhibit the benefits of cooperation with the government. In practice there were severe obstacles. The tribal medicine men launched a strong opposition, warning of white trickery and offering an alternative explanation and system of cure. Some taught that the affliction could best be cured by a sweat bath followed by a rapid plunge into cold water. Furthermore the vaccines often lost their potency when transported and stored over long distances with primitive storage facilities. It was too little and too late to avoid the great smallpox epidemic of 1837 to 1840 that swept across North America west of the Mississippi, all the way to Canada and Alaska. Deaths have been estimated in the range of 100,000 to 300,000, with entire tribes wiped out. Over 90 percent of the Mandans died. In the mid to late nineteenth century, at a time of increasing European-American travel and settlement in the West, at least four different epidemics broke out among the Plains tribes between 1837 and 1870. When the Plains tribes began to learn of the "white man's diseases", many intentionally avoided contact with them and their trade goods. But the lure of trade goods such as metal pots, skillets, and knives sometimes proved too strong. The Indians traded with the white newcomers anyway and inadvertently spread disease to their villages. In the late 19th century, the Lakota Indians of the Plains called the disease the "rotting face sickness". The 1862 Pacific Northwest smallpox epidemic , which was brought from San Francisco to Victoria , devastated the indigenous peoples of the Pacific Northwest Coast , with a death rate of over 50% for the entire coast from Puget Sound to Southeast Alaska . In some areas the native population fell by as much as 90%. Some historians have described the epidemic as a deliberate genocide because the Colony of Vancouver Island and the Colony of British Columbia could have prevented the epidemic but chose not to, and in some ways facilitated it. In 1832 President Andrew Jackson signed Congressional authorization and funding to set up a smallpox vaccination program for Indian tribes. The goal was to eliminate the deadly threat of smallpox to a population with little or no immunity, and at the same time exhibit the benefits of cooperation with the government. In practice there were severe obstacles. The tribal medicine men launched a strong opposition, warning of white trickery and offering an alternative explanation and system of cure. Some taught that the affliction could best be cured by a sweat bath followed by a rapid plunge into cold water. Furthermore the vaccines often lost their potency when transported and stored over long distances with primitive storage facilities. It was too little and too late to avoid the great smallpox epidemic of 1837 to 1840 that swept across North America west of the Mississippi, all the way to Canada and Alaska. Deaths have been estimated in the range of 100,000 to 300,000, with entire tribes wiped out. Over 90 percent of the Mandans died. In the mid to late nineteenth century, at a time of increasing European-American travel and settlement in the West, at least four different epidemics broke out among the Plains tribes between 1837 and 1870. When the Plains tribes began to learn of the "white man's diseases", many intentionally avoided contact with them and their trade goods. But the lure of trade goods such as metal pots, skillets, and knives sometimes proved too strong. The Indians traded with the white newcomers anyway and inadvertently spread disease to their villages. In the late 19th century, the Lakota Indians of the Plains called the disease the "rotting face sickness". The 1862 Pacific Northwest smallpox epidemic , which was brought from San Francisco to Victoria , devastated the indigenous peoples of the Pacific Northwest Coast , with a death rate of over 50% for the entire coast from Puget Sound to Southeast Alaska . In some areas the native population fell by as much as 90%. Some historians have described the epidemic as a deliberate genocide because the Colony of Vancouver Island and the Colony of British Columbia could have prevented the epidemic but chose not to, and in some ways facilitated it. Many Native American tribes suffered high mortality and depopulation, averaging 25–50% of the tribes' members dead from disease. Additionally, some smaller tribes neared extinction after facing a severely destructive spread of disease. A specific example was what followed Cortés ' invasion of Mexico . Before his arrival, the Mexican population is estimated to have been around 25 to 30 million. Fifty years later, the Mexican population was reduced to 3 million, mainly by infectious disease. A 2018 study by Koch, Brierley, Maslin and Lewis concluded that an estimated "55 million indigenous people died following the European conquest of the Americas beginning in 1492." Estimates for the entire number of human lives lost during the Cocoliztli epidemics in New Spain have ranged from 5 to 15 million people, making it one of the most deadly disease outbreaks of all time. By 1700, fewer than 5,000 Native Americans remained in the southeastern coastal region of the United States. In Florida alone, an estimated 700,000 Native Americans lived there in 1520, but by 1700 the number was around 2,000. Some 21st-century climate scientists have suggested that a severe reduction of the indigenous population in the Americas and the accompanying reduction in cultivated lands during the 16th, 17th and 18th centuries may have contributed to a global cooling event known as the Little Ice Age . The loss of the population was so high that it was partially responsible for the myth of the Americas as "virgin wilderness". By the time significant European colonization was underway, native populations had already been reduced by 90%. This resulted in settlements vanishing and cultivated fields being abandoned. Since forests were recovering, the colonists had an impression of a land that was an untamed wilderness. Disease had both direct and indirect effects on deaths. High mortality meant that there were fewer people to plant crops, hunt game, and otherwise support the group. Loss of cultural knowledge transfer also affected the community as vital agricultural and food-gathering skills were not passed on to survivors. Missing the right time to hunt or plant crops affected the food supply, thus further weakening the community and making it more vulnerable to the next epidemic. Communities under such crisis were often unable to care for people who were disabled, elderly, or young. In summer 1639, a smallpox epidemic struck the Huron natives in the St. Lawrence and Great Lakes regions. The disease had reached the Huron tribes through French colonial traders from Québec who remained in the region throughout the winter. When the epidemic was over, the Huron population had been reduced to roughly 9,000 people, about half of what it had been before 1634. The Iroquois people, generally south of the Great Lakes, faced similar losses after encounters with French, Dutch and English colonists. During the 1770s, smallpox killed at least 30% (tens of thousands) of the Northwestern Native Americans. The smallpox epidemic of 1780–1782 brought devastation and drastic depopulation among the Plains Indians . By 1832, the federal government of the United States established a smallpox vaccination program for Native Americans. The Commissioner of Indian Affairs in 1839 reported on the casualties of the 1837 Great Plains smallpox epidemic : "No attempt has been made to count the victims, nor is it possible to reckon them in any of these tribes with accuracy; it is believed that if [the number 17,200 for the upper Missouri River Indians] was doubled, the aggregate would not be too large for those who have fallen east of the Rocky Mountains ." Historian David Stannard asserts that by "focusing almost entirely on disease ... contemporary authors increasingly have created the impression that the eradication of those tens of millions of people was inadvertent—a sad, but both inevitable and 'unintended consequence' of human migration and progress." He says that their destruction "was neither inadvertent nor inevitable", but the result of microbial pestilence and purposeful genocide working in tandem. Historian Andrés Reséndez says that evidence suggests "among these human factors, slavery has emerged as a major killer" of the indigenous populations of the Caribbean between 1492 and 1550, rather than diseases such as smallpox, influenza and malaria. Cholera is an acute diarrheal infection transmitted through ingesting water or food contaminated with the bacteria vibrio cholerae . Cholera was specific to Asia until 1817. By 1829, Cholera was documented in North America and quickly spread throughout regions in rural and urban America. Up until the 20th century, the origin of Cholera was unknown. Symptoms of Cholera are known for their fast and advanced nature. Symptoms of Cholera include nausea, diarrhea, and vomiting which contribute to dehydration, erratic heartbeat, and shriveled skin. These symptoms contributed to Cholera's high mortality rate. Some of the most significant Cholera outbreaks occurred during the 1800s (when the cause was still unknown). Cholera affected many communities throughout the United States , especially communities that lived in unsanitary conditions. One population that was affected by water-borne disease such as Cholera, were Native Americans. Even though Cholera changed every American's life, the nature of Cholera and how it spread through communities had large impacts on indigenous communities throughout history. Cholera reached the United States in 1829 when immigrants came to America searching for new jobs and opportunities. Cholera, because it mostly resulted from poor hygiene and filthy conditions, disproportionately affects lower-income populations living in unsanitary conditions. Native Americans who lived their lives on reservations found themselves drinking water that was contaminated with vibrio cholerae. Poor drinking water and sanitary conditions contributed to the widespread spread of Cholera cases in Native communities. One of the most notable Cholera epidemics happened in 1832. In May of 1832, an immigrant ship with Asiatic Cholera landed in Quebec . Cholera spread quickly from the northern ports of Quebec down to the Hudson and Lower Manhattan. The rapid spread of Cholera from northern ports marked the onset of epidemics in major cities such as New York. The Epidemic of 1832 has been referred to by historians as the plague of the 19th century. America, up until this point, was not very familiar with the effects of widespread diseases. Cholera is known for its ability to quickly spread and flourish in every environment. Because of this Cholera was found in almost every part of the country during this period. Cholera's impact during the 1832 epidemic was particularly profound on indigenous communities. Cholera spread to Native populations in 1832 through waterways. Cholera was a problem all over but more prevalent in communities situated near water. Native American communities were more prevalent near sources of water because they wanted to have an accessible source of drinking water Unfortunately, Cholera (bacterium cholerae) spread rapidly through these areas. Increasing the community's chances of being infected. Some communities had more severe Cholera outbreaks than others. The Lakota tribe , for instance, had a major Cholera outbreak and demographic devastation due to the disposal of waste in the Great Lakes, a water source they consistently used for drinking. Cholera outbreaks were more devastating primarily because indigenous communities had little forms of water filtration and lacked immunity to water-borne diseases. Due to a lack of immunity to water-borne disease, Native Americans suffered from higher mortality rates Lack of immunity and exposure to bodies of water contaminated by cholera contributed to higher mortality rates in indigenous communities during the 1832 epidemic. The Trail of Tears was the forced relocation of Native American tribes in the 1830s from Eastern Woodlands to the west of the Mississippi River . This relocation ordered by the government primarily targeted "the Cherokee, Choctaw, Chickasaw, Creek, and Seminole" nations Approximately 100,000 native Americans were removed from their families and 15,000 died during the removal and journey west. The journey west consisted of 5,045 miles across nine states. Many people lost their lives on this rigorous forced journey. Cholera was one of the reasons for the deaths of Native Americans during the Trail of Tears. Traveling by steamboat was a common way to travel and cholera was present in the waterways used by the steamboats. It is estimated that 5,000 Native Americans died of cholera on this journey to areas west of the Mississippi. Cholera reached the United States in 1829 when immigrants came to America searching for new jobs and opportunities. Cholera, because it mostly resulted from poor hygiene and filthy conditions, disproportionately affects lower-income populations living in unsanitary conditions. Native Americans who lived their lives on reservations found themselves drinking water that was contaminated with vibrio cholerae. Poor drinking water and sanitary conditions contributed to the widespread spread of Cholera cases in Native communities. One of the most notable Cholera epidemics happened in 1832. In May of 1832, an immigrant ship with Asiatic Cholera landed in Quebec . Cholera spread quickly from the northern ports of Quebec down to the Hudson and Lower Manhattan. The rapid spread of Cholera from northern ports marked the onset of epidemics in major cities such as New York. The Epidemic of 1832 has been referred to by historians as the plague of the 19th century. America, up until this point, was not very familiar with the effects of widespread diseases. Cholera is known for its ability to quickly spread and flourish in every environment. Because of this Cholera was found in almost every part of the country during this period. Cholera's impact during the 1832 epidemic was particularly profound on indigenous communities. Cholera spread to Native populations in 1832 through waterways. Cholera was a problem all over but more prevalent in communities situated near water. Native American communities were more prevalent near sources of water because they wanted to have an accessible source of drinking water Unfortunately, Cholera (bacterium cholerae) spread rapidly through these areas. Increasing the community's chances of being infected. Some communities had more severe Cholera outbreaks than others. The Lakota tribe , for instance, had a major Cholera outbreak and demographic devastation due to the disposal of waste in the Great Lakes, a water source they consistently used for drinking. Cholera outbreaks were more devastating primarily because indigenous communities had little forms of water filtration and lacked immunity to water-borne diseases. Due to a lack of immunity to water-borne disease, Native Americans suffered from higher mortality rates Lack of immunity and exposure to bodies of water contaminated by cholera contributed to higher mortality rates in indigenous communities during the 1832 epidemic.The Trail of Tears was the forced relocation of Native American tribes in the 1830s from Eastern Woodlands to the west of the Mississippi River . This relocation ordered by the government primarily targeted "the Cherokee, Choctaw, Chickasaw, Creek, and Seminole" nations Approximately 100,000 native Americans were removed from their families and 15,000 died during the removal and journey west. The journey west consisted of 5,045 miles across nine states. Many people lost their lives on this rigorous forced journey. Cholera was one of the reasons for the deaths of Native Americans during the Trail of Tears. Traveling by steamboat was a common way to travel and cholera was present in the waterways used by the steamboats. It is estimated that 5,000 Native Americans died of cholera on this journey to areas west of the Mississippi. The deadliest cholera outbreak happened in the 1850s Cholera outbreaks during the 1850s were widespread, but cases were highly concentrated in areas with dense populations. The outbreak lasted from 1852 to 1860. 23,000 deaths were recorded in Britain alone The outbreak in Britain led to immigrants fleeing their homes and immigrating to America. This started the third significant and most deadly spread of cholera in America. This outbreak spread through the Mississippi River. The spread through the Mississippi reached communities in St. Louis to New Orleans. [ citation needed ] Many Native American communities contracted Cholera when they used the Mississippi River for transportation. Native American death tolls reached record highs during the outbreak in the 1850s. An example of a moment that became a major transmission event for cholera among tribes was the annual Kiowa Sun Dance. Several tribes were in attendance including the Osage, Comanche, Southern Cheyenne, Arapaho, and Apache. Sarah Keyes, a historian who specializes in the 19th century wrote that "The disease was demographically devastating for many Native nations of the plains. For instance, by the end of the 1854 epidemic the Pawnee had lost as much as 25 percent of their population" (Keyes) The Pawnee tribe was not the only tribe that was devastated by Cholera in the 1850s. Cholera was highly transmissible and led to outbreaks among multiple tribes and indigenous communities. The population of many Native American tribes and communities were forever changed after the 1850 pandemic. It is true that health disparities and cholera still exist today, specifically in native american communities. Today there have been a reported 1.3 to 2 million cases across the world and 21,000 to 14,300 deaths (WHO) Limited access to clean water and poor healthcare infrastructure contribute to the Cholera cases and deaths we see today. A majority of the people who contract these diseases are from indigenous communities in the United States. Indigenous communities have been more susceptible to diseases like Cholera because of limited access to clean water. Today, recent studies have shown that one in 10 Indigenous Americans lack access to safe tap water or basic sanitation – without which a host of health conditions including Covid-19, diabetes, and gastrointestinal disease are more likely. Activists and tribal governments have spoken with public health agencies and organizations to address these healthcare disparities. Many activists have organized protests and discussions with government and health officials. Winona LaDuke is an example of one activist who has been trying to promote a sustainable and healthy environment and land for Native Americans on reservations. She has been involved in the White Earth Land Recovery Project which tries to address environmental inequities hurting Native American communities today. Even though Cholera pandemics are no longer a concern, unhealthy water conditions on reservations still present many diseases and issues for indigenous communities today. Epidemics killed a high portion of people with disabilities and also resulted in numerous people with disabilities. The material and societal realities of disability for Native American communities were tangible. Scarlet fever could result in blindness or deafness, and sometimes both. Smallpox epidemics led to blindness and depigmented scars. Many Native American tribes prided themselves in their appearance, and the resulting skin disfigurement of smallpox deeply affected them psychologically. Unable to cope with this condition, tribe members were said to have committed suicide . Paleo-scientists can see the expression of disease by looking at its effect on bones, yet this offers a limited view. Most common infectious diseases, such as those caused by microorganisms like staphylococcus and streptococcus cannot be seen in the bones. Tuberculosis and the two forms of syphilis are considered rare and their diagnosis via osteological analysis is controversial. To understand health at the community level, scientists and health experts look at diet, the incidence and prevalence of infections, hygiene and waste disposal. [ citation needed ] Most diseases came to the Americas from Europe and Asia. One exception is syphilis, which originated in the Americas before 1492. A form of tuberculosis has also been identified in pre-Columbian populations, by bacterial genome sequences collected from human remains in Peru, and was probably transmitted to humans through seal hunting . It is true that health disparities and cholera still exist today, specifically in native american communities. Today there have been a reported 1.3 to 2 million cases across the world and 21,000 to 14,300 deaths (WHO) Limited access to clean water and poor healthcare infrastructure contribute to the Cholera cases and deaths we see today. A majority of the people who contract these diseases are from indigenous communities in the United States. Indigenous communities have been more susceptible to diseases like Cholera because of limited access to clean water. Today, recent studies have shown that one in 10 Indigenous Americans lack access to safe tap water or basic sanitation – without which a host of health conditions including Covid-19, diabetes, and gastrointestinal disease are more likely. Activists and tribal governments have spoken with public health agencies and organizations to address these healthcare disparities. Many activists have organized protests and discussions with government and health officials. Winona LaDuke is an example of one activist who has been trying to promote a sustainable and healthy environment and land for Native Americans on reservations. She has been involved in the White Earth Land Recovery Project which tries to address environmental inequities hurting Native American communities today. Even though Cholera pandemics are no longer a concern, unhealthy water conditions on reservations still present many diseases and issues for indigenous communities today. Epidemics killed a high portion of people with disabilities and also resulted in numerous people with disabilities. The material and societal realities of disability for Native American communities were tangible. Scarlet fever could result in blindness or deafness, and sometimes both. Smallpox epidemics led to blindness and depigmented scars. Many Native American tribes prided themselves in their appearance, and the resulting skin disfigurement of smallpox deeply affected them psychologically. Unable to cope with this condition, tribe members were said to have committed suicide . Paleo-scientists can see the expression of disease by looking at its effect on bones, yet this offers a limited view. Most common infectious diseases, such as those caused by microorganisms like staphylococcus and streptococcus cannot be seen in the bones. Tuberculosis and the two forms of syphilis are considered rare and their diagnosis via osteological analysis is controversial. To understand health at the community level, scientists and health experts look at diet, the incidence and prevalence of infections, hygiene and waste disposal. [ citation needed ] Most diseases came to the Americas from Europe and Asia. One exception is syphilis, which originated in the Americas before 1492. A form of tuberculosis has also been identified in pre-Columbian populations, by bacterial genome sequences collected from human remains in Peru, and was probably transmitted to humans through seal hunting .

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2023–2024_Zambian_cholera_outbreak/html

2023–2024 Zambian cholera outbreak

The 2023–2024 Zambian cholera outbreak , part of the 2022–2024 Southern Africa cholera outbreak , is currently one of the most severe health crises in the country's recent history, with its origins traced back to January 2023. The outbreak initially surfaced in Vubwi District in the Eastern Province and Mwansabombwe District in Luapula Province . By October 2023, the Zambia National Public Health Institute reported a cholera outbreak in the capital, Lusaka . Cholera cases have so far broken out in 15 districts in five out of the country's 10 provinces , with Lusaka, the country's capital recording the highest number of cases. Of particular concern is the rapid progression of the outbreak within Lusaka, where, within a week, the Ministry of Health reported a surge of 71.2% in cases and a staggering 175% increase in fatalities. Partners affiliated with DG ECHO actively collaborate with the Ministry of Health, providing crucial support in various capacities. Initiatives include community sensitization and risk communication, distribution and control of chlorine at critical water points, contact tracing, and the management of oral rehydration points within Lusaka. There is an urgent imperative to intensify community engagement and bolster the supply of safe water in affected areas, coupled with continuous monitoring of water quality. Cholera, a waterborne bacterial infection, has been a recurring health challenge in Zambia. The current outbreak has been identified as potentially the worst since the first recorded outbreak in 1977. The rapid spread of the disease has led to increased efforts by health workers to contain the crisis and provide essential medical assistance to those affected. President Hakainde Hichilema has called for the relocation of people from towns to villages, citing poor sanitation in densely populated urban areas as a significant factor contributing to the outbreak. The President's directive is aimed at minimizing the risk of further infections and creating a safer environment in rural areas. Family gatherings during funerals have been identified as potential hotspots for cholera transmission. In response, the Zambian Health Ministry has prohibited funerals and family burials. Health Minister Sylvia Masebo emphasized the importance of adhering to these measures to prevent the spread of the disease. "I've told them that they cannot participate in burials, and I also told them that they cannot have funerals at their homes. I also told the general public not to attend funerals anymore," stated Sylvia Masebo. [ citation needed ] In response to the escalating crisis, Health Minister Sylvia Masebo revealed that the National Heroes Stadium in Lusaka, with a seating capacity of 60,000, has been repurposed as a treatment center for cholera. This decision aims to alleviate the strain on existing health facilities grappling with the surge in cholera cases. Masebo, emphasizing proactive measures, stated, "We continue sensitizing our citizens not to buy food from unsafe locations and to observe the highest level of hygiene so that together we can curb the spread of cholera." To reinforce this message, a mass sensitization roadshow was conducted in Lusaka on Thursday. In an additional measure to curb the spread of the disease, vending on the streets has been prohibited, as announced last week. These collective efforts underscore the gravity of the public health situation and the commitment of authorities to mitigate the impact of the cholera outbreak in Zambia. Africa Centres for Disease Control and Prevention has played a role in supporting Zambia's response to the cholera outbreak by deploying technical assistance officers, coordinating with key partners, and providing financial assistance. The organization is actively engaged in various interventions, including training healthcare workers, strengthening laboratory capacity, and procuring essential medical supplies to control and end the cholera crisis. In a determined effort to combat the cholera outbreak, Zambia initiated an extensive oral cholera vaccination campaign on January 16, 2024, concentrating efforts on the hotspots within the capital city of Lusaka, which has borne the brunt of the ongoing crisis. The campaign commenced with the distribution and administration of 1.4 million doses received on January 15, 2024 from the World Health Organization (WHO), which has allocated a total of 1.7 million doses to Zambia. The launch event took place in George Township, Lusaka, and was officiated by Zambia's Health Minister, Sylvia Masebo. Acknowledging the constraint in vaccine availability, Masebo announced that residents would receive a single dose instead of the recommended two doses. Notably, the vaccination program is also extended to health workers actively engaged in the frontline battle against cholera. President Hakainde Hichilema has called for the relocation of people from towns to villages, citing poor sanitation in densely populated urban areas as a significant factor contributing to the outbreak. The President's directive is aimed at minimizing the risk of further infections and creating a safer environment in rural areas. Family gatherings during funerals have been identified as potential hotspots for cholera transmission. In response, the Zambian Health Ministry has prohibited funerals and family burials. Health Minister Sylvia Masebo emphasized the importance of adhering to these measures to prevent the spread of the disease. "I've told them that they cannot participate in burials, and I also told them that they cannot have funerals at their homes. I also told the general public not to attend funerals anymore," stated Sylvia Masebo. [ citation needed ]In response to the escalating crisis, Health Minister Sylvia Masebo revealed that the National Heroes Stadium in Lusaka, with a seating capacity of 60,000, has been repurposed as a treatment center for cholera. This decision aims to alleviate the strain on existing health facilities grappling with the surge in cholera cases. Masebo, emphasizing proactive measures, stated, "We continue sensitizing our citizens not to buy food from unsafe locations and to observe the highest level of hygiene so that together we can curb the spread of cholera." To reinforce this message, a mass sensitization roadshow was conducted in Lusaka on Thursday. In an additional measure to curb the spread of the disease, vending on the streets has been prohibited, as announced last week. These collective efforts underscore the gravity of the public health situation and the commitment of authorities to mitigate the impact of the cholera outbreak in Zambia. Africa Centres for Disease Control and Prevention has played a role in supporting Zambia's response to the cholera outbreak by deploying technical assistance officers, coordinating with key partners, and providing financial assistance. The organization is actively engaged in various interventions, including training healthcare workers, strengthening laboratory capacity, and procuring essential medical supplies to control and end the cholera crisis. In a determined effort to combat the cholera outbreak, Zambia initiated an extensive oral cholera vaccination campaign on January 16, 2024, concentrating efforts on the hotspots within the capital city of Lusaka, which has borne the brunt of the ongoing crisis. The campaign commenced with the distribution and administration of 1.4 million doses received on January 15, 2024 from the World Health Organization (WHO), which has allocated a total of 1.7 million doses to Zambia. The launch event took place in George Township, Lusaka, and was officiated by Zambia's Health Minister, Sylvia Masebo. Acknowledging the constraint in vaccine availability, Masebo announced that residents would receive a single dose instead of the recommended two doses. Notably, the vaccination program is also extended to health workers actively engaged in the frontline battle against cholera. The cholera outbreak has had significant repercussions on the nation's education sector and prompted stringent public health interventions. In response to the escalating crisis, authorities decided to postpone the reopening of schools by an additional three weeks, as announced by the Education Minister, Douglas Syakalima , on Thursday. Syakalima informed reporters in the capital, Lusaka, that both public and private early childhood, primary, and secondary schools will remain closed beyond the initially scheduled opening date of January 8, 2024. Consequently, the revised date for school resumption is now set for Monday, January 29. This measure aims to safeguard the health and well-being of students and staff in the face of the ongoing cholera outbreak. On January 24, 2024, Zambia declared an additional two-week extension of school closures, with a revised reopening date of February 12, citing the escalating spread of cholera throughout the nation, notably in the capital city of Lusaka. Originally scheduled to resume on January 8, the reopening of schools had already been postponed to January 29 due to the prevailing cholera outbreak. "In light of the escalating cholera cases affecting various parts of the country, the national disaster management and mitigation council of ministers, in a meeting held this morning, advised the Ministry of Education to further defer the opening date to Feb. 12," disclosed Education Minister Douglas Syakalima during a press conference in Lusaka. The Health Ministry reported that Zambia has documented 13,686 cholera cases since the outbreak began in October of the previous year, resulting in 518 fatalities and 12,365 recoveries. As of January 24, 801 patients are still undergoing treatment in hospitals. The cholera outbreak has had significant repercussions on the nation's education sector and prompted stringent public health interventions. In response to the escalating crisis, authorities decided to postpone the reopening of schools by an additional three weeks, as announced by the Education Minister, Douglas Syakalima , on Thursday. Syakalima informed reporters in the capital, Lusaka, that both public and private early childhood, primary, and secondary schools will remain closed beyond the initially scheduled opening date of January 8, 2024. Consequently, the revised date for school resumption is now set for Monday, January 29. This measure aims to safeguard the health and well-being of students and staff in the face of the ongoing cholera outbreak. On January 24, 2024, Zambia declared an additional two-week extension of school closures, with a revised reopening date of February 12, citing the escalating spread of cholera throughout the nation, notably in the capital city of Lusaka. Originally scheduled to resume on January 8, the reopening of schools had already been postponed to January 29 due to the prevailing cholera outbreak. "In light of the escalating cholera cases affecting various parts of the country, the national disaster management and mitigation council of ministers, in a meeting held this morning, advised the Ministry of Education to further defer the opening date to Feb. 12," disclosed Education Minister Douglas Syakalima during a press conference in Lusaka. The Health Ministry reported that Zambia has documented 13,686 cholera cases since the outbreak began in October of the previous year, resulting in 518 fatalities and 12,365 recoveries. As of January 24, 801 patients are still undergoing treatment in hospitals.

Wiki

Cholera

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

Siege of Mariupol

Russian Armed Forces Ukrainian Armed Forces Inside Mariupol: Other involved units: The siege of Mariupol began on 24 February 2022 and lasted until 20 May, as part of the Russian invasion of Ukraine . It saw fighting between the Russian Armed Forces (alongside the Donetsk People's Republic People's Militia ) and the Ukrainian Armed Forces for control over the city of Mariupol in southeastern Ukraine. Lasting for almost three months, the siege ended in a victory for Russia and the Donetsk People's Republic , as Ukraine lost control of the city amidst Russia's eastern Ukraine offensive and southern Ukraine offensive ; all Ukrainian troops remaining in the city surrendered at the Azovstal Iron and Steel Works on 20 May 2022, after they were ordered to cease fighting. Mariupol is located in Ukraine's Donetsk Oblast , and following the siege, it was initially controlled by the Donetsk People's Republic , supported by occupying Russian troops. However, it was later subjected to Russia's unilateral annexation of southeastern Ukraine , and remains under direct Russian control as of 10 May 2023 [ update ] . During the Russian siege, the Red Cross described the situation in Mariupol as "apocalyptic" while Ukrainian authorities accused Russia of engineering a major humanitarian crisis in the city. Ukrainian officials reported that approximately 25,000 civilians had been killed and that at least 95% of the city had been destroyed during the fighting, primarily by large-scale Russian bombardments. In an official statement, the United Nations confirmed the deaths of 1,348 civilians in Mariupol, but warned that the true death toll was likely thousands higher while also reporting that 90% of the city's residential buildings had been damaged or completely destroyed. Major combat operations in the city effectively ended on 16 May 2022, after Ukraine's Azov Regiment surrendered at the Azovstal Iron and Steel Works. Some Western reports described the siege as a pyrrhic or symbolic Russian victory, with others noting that the humanitarian impact of the takeover was a "reputational disaster" for Russia. However, the loss of the city has also been seen as a significant defeat for Ukraine. Based on the analysis of mass graves, Human Rights Watch estimated at least 10,284 people died in Mariupol from March 2022 to February 2023, but assumes that is an undercount. Mariupol was considered a major strategic city and therefore was a target for Russian forces. It was the largest city in the Ukrainian-controlled portion of Donetsk Oblast , [lower-alpha 5] and was also one of the largest Russian-speaking cities in Ukraine. Mariupol was a major industrial hub, home of the Illich and Azovstal Iron and Steel Works , and the largest city on the Sea of Azov . Control of its port on the western shore of the Sea of Azov is vital to the economy of Ukraine. For Russia, it would allow a land route to Crimea and allow passage by Russian marine traffic. Capturing the city gave Russia full control over the Sea of Azov. In 2014 after the Revolution of Dignity , Mariupol was swept by pro-Russian protests against the new government . Tensions erupted into the war in Donbas in early May, and during the unrest, militiamen of the separatist and Russian-backed Donetsk People's Republic (DPR) took control of the city and forced Ukrainian troops to abandon it during the first battle for Mariupol . However, the following month, Ukrainian forces recaptured the city in an offensive. In August, the DPR and Russian troops captured the village of Novoazovsk , 45 km east of Mariupol near the Russo-Ukrainian border . With the town captured and forces renewed, in September the DPR attempted to capture the city again in the second battle for Mariupol . Fighting reached the eastern outskirts, but the separatists were eventually repelled. In October, then- DPR Prime Minister Alexander Zakharchenko vowed to retake the city. Mariupol was then indiscriminately bombed by rockets in January 2015. Fearing a future third offensive into Mariupol, in February Ukrainian forces launched a surprise attack into Shyrokyne , a village located 11 km east of Mariupol with the objective of expelling the separatist forces from the city limits and creating a buffer zone. The separatists withdrew from Shyrokyne four months later. The conflict was frozen when the Minsk II ceasefire agreement was signed in 2015. 2018 saw again tension in the region around Mariupol, as the Russian Federal Security Service (FSB) coast guard fired upon and captured three Ukrainian Navy vessels after they attempted to transit from the Black Sea into the Sea of Azov through the Kerch Strait on their way to the port of Mariupol. The Kerch Strait incident raised tensions, and martial law was briefly declared by Ukraine in fears that a war would break out between the two countries. One of the most instrumental groups for the recapture and subsequent defenses of Mariupol was the Azov Battalion , a Ukrainian volunteer militia , controversial for its openly neo-Nazi and ultranationalist members. By November 2014 Azov was integrated into the National Guard of Ukraine , with Mariupol as its headquarters. As one of Vladimir Putin 's stated goals for the invasion was the " denazification " of Ukraine, Mariupol represented an important ideological and symbolical target for the Russian forces. Prior to the siege, around 100,000 residents left Mariupol, according to the city's deputy mayor. Prior to falling to Russian forces, the city was defended by the Ukrainian Ground Forces , the Ukrainian Naval Infantry , the National Guard of Ukraine (primarily the Azov Regiment ), the Territorial Defense Forces of Ukraine , and irregular forces. On 24 February, the day the invasion began, Russian artillery bombarded the city, reportedly injuring 26 people. On the morning of 25 February, Russian forces advanced from DPR territory in the east towards Mariupol. They encountered Ukrainian forces near the village of Pavlopil , whom repelled the Russian advance. The mayor of Mariupol, Vadym Boychenko , said 22 Russian tanks had been destroyed in the skirmish. That evening, the Russian Navy , drawing on the capabilities provided by the Black Sea Fleet , reportedly began an amphibious assault on the Sea of Azov coastline 70 kilometres (43 mi) west of Mariupol. A US defense official stated that the Russians may have deployed thousands of marines from this beachhead . On 26 February, Russian forces continued to bombard Mariupol with artillery. Later, the government of Greece announced that ten ethnic Greek civilians had been killed by Russian strikes at Mariupol, six in the village of Sartana and four in the village of Buhas. On the morning of 27 February, mayor Boychenko said that a Russian tank column had advanced on Mariupol from the DPR, but this attack was repulsed by Ukrainian forces, with six Russian soldiers captured. Later that day, a 6-year-old girl in Mariupol was killed by Russian shelling. Pavlo Kyrylenko , governor of Donetsk Oblast , stated that fighting in Mariupol had continued throughout the night of 27 February. Throughout 28 February, the city remained under Ukrainian control despite being surrounded by Russian troops and constantly shelled. Electricity, gas, and internet connection to most of the city was cut during the evening. Later, according to Radio Free Europe/Radio Liberty , Russian Major General Andrei Sukhovetsky was killed by a Ukrainian sniper near Mariupol, but other sources [ clarification needed ] said that he had been killed during the Kyiv offensive . On 1 March, Denis Pushilin , the head of the DPR , announced that DPR forces had almost completely surrounded the nearby city of Volnovakha and that they would soon do the same to Mariupol. Russian artillery later bombarded Mariupol, causing over 21 injuries. The city was fully surrounded on 2 March, after which the siege intensified. Russian shelling killed a teenager and wounded two other teenagers who were playing soccer outside. Boychenko announced the city was suffering from a water outage and had experienced massive casualties. He also said Russian forces were preventing civilians from exiting. Later on 2 March, Russian artillery targeted a densely populated neighborhood of Mariupol, shelling it for nearly 15 hours. The neighborhood was massively damaged as a result, with deputy mayor Sergiy Orlov reporting that "at least hundreds of people are dead". On the morning of 3 March, the city was shelled again by Russian troops. Eduard Basurin , the spokesman for the DPR militia , formally called on the besieged Ukrainian forces in Mariupol to surrender or face "targeted strikes". Russian Ministry of Defense spokesman Igor Konashenkov reported that DPR forces had tightened the siege, and that three nearby settlements had been captured. On 4 March, Boychenko stated that the city's supplies were running out, and called for a humanitarian evacuation corridor and Ukrainian military reinforcements. He also stated that Russian BM-21 Grads were shelling the city's hospitals and that Mariupol residents no longer had heat, running water, or electricity. Later that day, a temporary ceasefire was proposed for the Mariupol region in order to allow citizens to evacuate. On 5 March, the Ukrainian government announced its desire to evacuate 200,000 civilians from Mariupol. The International Committee of the Red Cross (ICRC) announced that it would act as a guarantor for a new ceasefire to allow for this evacuation. The Red Cross described the situation in Mariupol as "extremely dire". After three days of shelling, a ceasefire was announced to be in effect from 11:00 to 16:00. Civilians began to evacuate from Mariupol along a humanitarian corridor to the city of Zaporizhzhia . As civilians entered the evacuation corridor, Russian forces continued shelling the city, forcing evacuees to turn back. Ukrainian authorities later reported that Russian forces had failed to observe the ceasefire and continued to shell the city. Russian officials accused Ukrainian forces of not allowing civilians to evacuate towards Russia. The DPR reported that only 17 civilians had been evacuated from Mariupol. On 6 March, the Red Cross announced that a second attempt to evacuate civilians from Mariupol had again failed. Anton Herashchenko , a Ukrainian official, said the second attempt at a humanitarian corridor for civilians in Mariupol ended with a Russian bombardment. The Red Cross reported that there were "devastating scenes of human suffering" in Mariupol. Later in the morning, Inna Sovsun , a Ukrainian member of parliament, stated that the fuel pipeline that supplies Mariupol was damaged by Russian forces, leaving more than 700,000 people without heat, and suggested that people might freeze to death, as the temperature at the time often fell below 0 °C (32 °F) . The bombardment also hit the city's last functioning cellular tower . On 7 March, the ICRC Director of Operations stated that humanitarian corridor agreements had only been made in principle, without the precision required for implementation, needing routes, times and whether goods could be brought in to be agreed. The ICRC team had found that one of the proposed corridor roads was mined, and the ICRC was facilitating talks between Russian and Ukrainian forces. On 8 March, another attempt to evacuate civilians was made, but the Ukrainian government accused Russia of violating the ceasefire again by bombing the evacuation corridor. On 9 March, the Associated Press reported that scores of Ukrainian civilians and soldiers were being buried by city workers in a mass grave at one of the city's cemeteries. Russian shelling had hit the cemetery the previous day, interrupting the burials and damaging a wall. Later, another attempted ceasefire failed after Orlov reported that Russian soldiers had opened fire on construction workers and evacuation points. Orlov described the city's supply shortage as so severe that residents were melting snow to get water. Later that day, the Mariupol City Council issued a statement that a Russian airstrike had struck and destroyed a maternity ward and children's hospital . Ukrainian officials stated that three civilians were killed and at least 17 wounded. On 24 February, the day the invasion began, Russian artillery bombarded the city, reportedly injuring 26 people. On the morning of 25 February, Russian forces advanced from DPR territory in the east towards Mariupol. They encountered Ukrainian forces near the village of Pavlopil , whom repelled the Russian advance. The mayor of Mariupol, Vadym Boychenko , said 22 Russian tanks had been destroyed in the skirmish. That evening, the Russian Navy , drawing on the capabilities provided by the Black Sea Fleet , reportedly began an amphibious assault on the Sea of Azov coastline 70 kilometres (43 mi) west of Mariupol. A US defense official stated that the Russians may have deployed thousands of marines from this beachhead . On 26 February, Russian forces continued to bombard Mariupol with artillery. Later, the government of Greece announced that ten ethnic Greek civilians had been killed by Russian strikes at Mariupol, six in the village of Sartana and four in the village of Buhas. On the morning of 27 February, mayor Boychenko said that a Russian tank column had advanced on Mariupol from the DPR, but this attack was repulsed by Ukrainian forces, with six Russian soldiers captured. Later that day, a 6-year-old girl in Mariupol was killed by Russian shelling. Pavlo Kyrylenko , governor of Donetsk Oblast , stated that fighting in Mariupol had continued throughout the night of 27 February. Throughout 28 February, the city remained under Ukrainian control despite being surrounded by Russian troops and constantly shelled. Electricity, gas, and internet connection to most of the city was cut during the evening. Later, according to Radio Free Europe/Radio Liberty , Russian Major General Andrei Sukhovetsky was killed by a Ukrainian sniper near Mariupol, but other sources [ clarification needed ] said that he had been killed during the Kyiv offensive . On 1 March, Denis Pushilin , the head of the DPR , announced that DPR forces had almost completely surrounded the nearby city of Volnovakha and that they would soon do the same to Mariupol. Russian artillery later bombarded Mariupol, causing over 21 injuries. The city was fully surrounded on 2 March, after which the siege intensified. Russian shelling killed a teenager and wounded two other teenagers who were playing soccer outside. Boychenko announced the city was suffering from a water outage and had experienced massive casualties. He also said Russian forces were preventing civilians from exiting. Later on 2 March, Russian artillery targeted a densely populated neighborhood of Mariupol, shelling it for nearly 15 hours. The neighborhood was massively damaged as a result, with deputy mayor Sergiy Orlov reporting that "at least hundreds of people are dead". On the morning of 3 March, the city was shelled again by Russian troops. Eduard Basurin , the spokesman for the DPR militia , formally called on the besieged Ukrainian forces in Mariupol to surrender or face "targeted strikes". Russian Ministry of Defense spokesman Igor Konashenkov reported that DPR forces had tightened the siege, and that three nearby settlements had been captured. On 4 March, Boychenko stated that the city's supplies were running out, and called for a humanitarian evacuation corridor and Ukrainian military reinforcements. He also stated that Russian BM-21 Grads were shelling the city's hospitals and that Mariupol residents no longer had heat, running water, or electricity. Later that day, a temporary ceasefire was proposed for the Mariupol region in order to allow citizens to evacuate. On 5 March, the Ukrainian government announced its desire to evacuate 200,000 civilians from Mariupol. The International Committee of the Red Cross (ICRC) announced that it would act as a guarantor for a new ceasefire to allow for this evacuation. The Red Cross described the situation in Mariupol as "extremely dire". After three days of shelling, a ceasefire was announced to be in effect from 11:00 to 16:00. Civilians began to evacuate from Mariupol along a humanitarian corridor to the city of Zaporizhzhia . As civilians entered the evacuation corridor, Russian forces continued shelling the city, forcing evacuees to turn back. Ukrainian authorities later reported that Russian forces had failed to observe the ceasefire and continued to shell the city. Russian officials accused Ukrainian forces of not allowing civilians to evacuate towards Russia. The DPR reported that only 17 civilians had been evacuated from Mariupol. On 6 March, the Red Cross announced that a second attempt to evacuate civilians from Mariupol had again failed. Anton Herashchenko , a Ukrainian official, said the second attempt at a humanitarian corridor for civilians in Mariupol ended with a Russian bombardment. The Red Cross reported that there were "devastating scenes of human suffering" in Mariupol. Later in the morning, Inna Sovsun , a Ukrainian member of parliament, stated that the fuel pipeline that supplies Mariupol was damaged by Russian forces, leaving more than 700,000 people without heat, and suggested that people might freeze to death, as the temperature at the time often fell below 0 °C (32 °F) . The bombardment also hit the city's last functioning cellular tower . On 7 March, the ICRC Director of Operations stated that humanitarian corridor agreements had only been made in principle, without the precision required for implementation, needing routes, times and whether goods could be brought in to be agreed. The ICRC team had found that one of the proposed corridor roads was mined, and the ICRC was facilitating talks between Russian and Ukrainian forces. On 8 March, another attempt to evacuate civilians was made, but the Ukrainian government accused Russia of violating the ceasefire again by bombing the evacuation corridor. On 9 March, the Associated Press reported that scores of Ukrainian civilians and soldiers were being buried by city workers in a mass grave at one of the city's cemeteries. Russian shelling had hit the cemetery the previous day, interrupting the burials and damaging a wall. Later, another attempted ceasefire failed after Orlov reported that Russian soldiers had opened fire on construction workers and evacuation points. Orlov described the city's supply shortage as so severe that residents were melting snow to get water. Later that day, the Mariupol City Council issued a statement that a Russian airstrike had struck and destroyed a maternity ward and children's hospital . Ukrainian officials stated that three civilians were killed and at least 17 wounded. Ukraine's military stated on 12 March that Russian forces had captured the eastern outskirts of Mariupol. Later, a vehicle convoy of 82 ethnic Greeks was able to leave the city via a humanitarian corridor. On 13 March, Boychenko stated that Russian forces had bombed the city at least 22 times in the previous 24 hours, with a hundred bombs, and added that the last food and water reserves in the city were being depleted. The Ukrainian Ministry of Internal Affairs said that the National Guard of Ukraine had damaged several Russian armored vehicles with artillery strikes during the day. İsmail Hacıoğlu, the head of the local Sultan Suleiman Mosque , stated that 86 Turkish citizens in the city were awaiting evacuation by the Turkish government. More than 160 cars were able to leave the city on 14 March at 13:00 local time, the first evacuation allowed during the siege. The Russian Ministry of Defense stated that 450 tonnes of humanitarian aid had been brought to the city after Russian forces captured the outskirts. Ukrainian military officials were later said to have killed 150 Russian soldiers and destroyed 10 Russian vehicles. On the same day, Ramzan Kadyrov , the head of Chechnya , stated that Chechen soldiers were participating in the siege and had briefly entered Mariupol before retreating. Kadyrov also stated that Adam Delimkhanov , a close ally and member of the State Duma , was the commander of Chechen forces in Mariupol. The funeral for Captain Alexey Glushchak of the GRU was held in Tyumen , and it was revealed he died near Mariupol, likely in the early stages of the siege. On 15 March, around 4,000 vehicles with about 20,000 civilians were able to leave the city. Ukrainian government official Anton Herashchenko said that Russian Major General Oleg Mityaev , commander of the 150th Motorized Rifle Division , was killed when Russian forces tried to storm the city. The Donetsk Regional Drama Theatre , sheltering hundreds of civilians, was hit by a Russian airstrike on 16 March and destroyed. Pavlo Kyrylenko , the governor of Donetsk Oblast, later stated that Russian forces had also targeted the Neptune swimming pool. On 18 March, DPR forces said they had captured the Mariupol airport from Ukrainian forces. Clashes later reached the city center, according to the mayor and on 19 March, Russian and Ukrainian forces began fighting at the Azovstal steel plant. On the same day, President Volodymyr Zelensky awarded Colonel Volodymyr Baranyuk and Major Denys Prokopenko , leaders of the defense in Mariupol, the honor of Hero of Ukraine , the country's highest military award. During this time, while attempting to transport the killed and wounded to the hospital at Azovstal, Major Mykyta Nadtochii, commander of the Azov Regiment's second battalion, was wounded in a Russian airstrike. On 20 March, the city council of Mariupol claimed Russian forces had forcefully deported "several thousand" people to camps and remote cities in Russia over the past week. Russia denied the accusation. The same day, an art school building, which had sheltered some 400 people, was destroyed in a Russian bombing . No information on casualties was immediately available. An order by Russia's Ministry of Defence to surrender, lay down arms and evacuate the city was submitted on 20 March, requesting a written response by 02:00 UTC the next day. The ultimatum was rejected by the Ukrainian government and the mayor of Mariupol. By this point, one of the Ukrainian battalion commanders in the city described "bombs falling every 10 minutes". On 21 March, the first helicopter evacuation from Azovstal took place as eight or nine seriously wounded soldiers were evacuated, including the wounded Major Nadtochii. Two Ukrainian Mil Mi-8 helicopters flew into Azovstal as part of "Operation Air Corridor", carrying a special forces team with crates of Stinger and Javelin missiles, as well as a satellite internet system. "Operation Air Corridor" lasted until 7 April, when one helicopter was shot down, followed by the shooting down of a second helicopter that was sent as part of rescue efforts to search for survivors of the first downing. The four special forces members on board the second helicopter were killed, along with the helicopter's crew. Ukraine claimed 85 seriously wounded soldiers were evacuated as part of "Operation Air Corridor" during seven missions to the Azovstal plant to resupply or deliver reinforcements using some 16 Mi-8s, in pairs or fours, two of which were shot down, along with the rescue helicopter, according to Major General Kyrylo Budanov . In contrast, Ukrainian president Zelensky stated 90 percent of helicopter pilots sent to Mariupol during the course of the siege to resupply Ukrainian forces and evacuate the wounded were lost due to Russian air-defenses. According to Russia, one Ukrainian Mil Mi-8 helicopter was shot down on 28 March, as it was heading to Mariupol to evacuate the leaders of the Azov Regiment. In addition, Russia reported its forces shot down two more Ukrainian Mi-8s on 5 April, as they were once again attempting to evacuate Azov commanders. The Times later reported, after interviewing Ukrainian participants, that from 21 March to 11 May, 15 helicopters and 45 aircrew made nearly 30 attempted rescue missions delivering ammunition, equipment, medicine and evacuating wounded, with 6 flights being successful and 3 helicopters shot down with 23 killed in one crash. On 23 March, local authorities, including the mayor, left the city due to the deteriorating situation. The following day, Russian forces entered central Mariupol, seizing the Orthodox Church of the Intercession of the Mother of God. The city administration alleged that Russians were trying to demoralize residents by publicly shouting claims of Russian victories, including statements that Odesa had been captured. Vadym Boychenko said on 27 March that while Mariupol was still under Ukrainian control, Russian forces had entered deep into the city and that the city's population needed a "complete evacuation". By this point, Ukrainian soldiers had run out of food and clean drinking water, and an analyst believed that Ukrainian forces would not be able to fight on beyond a few days. However, Ukrainian officers refused to evacuate from the city, as they did not want to abandon their wounded and dead soldiers and civilians. The "Club 8bit" computer museum was destroyed. On 28 March, Mayor Vadym Boychenko said "we are in the hands of the occupiers today" in a televised interview, and a spokesman for the Mariupol mayor's office announced that "nearly 5,000 people" had been killed in the city since the start of the siege. The Ukrainian government estimated that "from 20,000 to 30,000" Mariupol residents had been forcibly sent to camps in Russia under Russian military control. During the day, Russian forces seized the administrative building in the northern Kalmiuskyi District and the military headquarters of the Azov Regiment. The next day, Russian forces were reported to have likely divided Ukrainian troops in the city into two and possibly even three pockets. On 2 April, Russian forces captured the SBU building in central Mariupol, after which there was no more reported fighting in the area. On 4 April, one Ukrainian battalion surrendered, with Russian officials stating two days later they captured 267 Ukrainian marines from the 503rd Battalion of the Ukrainian Naval Forces . Due to the surrender, the lines between the Ukrainian 36th Separate Marine Brigade and the Azov Regiment had been broken. On 7 April, the DPR announced central Mariupol had been cleared of Ukrainian forces. Meanwhile, Russian troops started an advance from the southwest on 1 April, leaving the Ukrainian military in partial control of the area around the port in the southwest of Mariupol by 7 April. On 4 April, a Russian Navy missile hit a Malta -based Dominica -flagged cargo ship, resulting in the ship catching fire. In addition, on 7 April, Russian forces captured a bridge leading to the Azovstal steel plant. The following day, Russian troops seized the southern part of Mariupol's port. On 10 April, Russian forces captured the fishing port, separating Ukrainian troops in the port from those in the Azovstal steel plant into two pockets, while a possible third pocket was centered on the Illich steel plant to the north. The next day, DPR forces claimed to have captured 80% of Mariupol. Local Ukrainian forces expected the city to fall soon, since they were running out of ammunition, and analysts at the Institute for the Study of War believed that Mariupol would fall within a week. On 11 April, Russian media reported that 160 Ukrainian servicemen from the 36th Separate Marine Brigade were captured with their equipment. During the night between 11 and 12 April, Baranyuk led the 36th Separate Marine Brigade in an attempt to break out of the Russian encirclement at the Illich steel plant to the north. After being spotted they broke into smaller groups, with some of them managing to link up with fighters of the Azov Regiment at the Azovstal plant to the southeast. A large number of Ukrainian servicemen were either killed or captured during the breakout. The fate of Baranyuk initially remained unknown. Later, the DPR claimed that they had identified the body of Baranyuk after their special forces blocked the Ukrainian breakout. However, on 8 May, Baranyuk appeared alive in an interview with RT , along with the 36th Brigade's Chief of Staff Dmytro Kormiankov. They were reported to have been captured during the breakout attempt. Around the same time at 11 April, a 16-man detachment from a battalion of tankers of the 17th Tank Brigade , which were doing operations supporting the 36th Brigade, did not follow Baranyuk's plan and instead broke through the siege. They used two tanks, anti-aircraft guns and cars for transport, and after breaking out they proceeded on foot for 175 km until reaching friendly Ukrainian positions. For leading his men to safety, the unit's commander, Lieutenant Colonel Oleg Grudzevych, was awarded a Hero of Ukraine medal. On 12 April, Aiden Aslin , a British man fighting with the Ukrainian Marines, reported that his unit was going to surrender since they had run out of ammunition, food and other supplies. Subsequently, in the evening, Russia stated that 1,026 Marines of the 36th Separate Marine Brigade had surrendered at the Illich steel plant, including 162 officers and 400 wounded fighters. Later, Russia said it captured an additional 134 Ukrainian servicemen, bringing the total number of prisoners to 1,160. Ukraine confirmed nearly 1,000 Marines had been captured, including wounded and those who remained at the Illich plant. On 13 April, Russian forces secured the Illich plant, reducing the number of pockets in Mariupol to two, while Russia also announced it had taken full control of Mariupol's commercial port, which was confirmed three days later. The commander of the Azov Regiment, Prokopenko, criticized the servicemen that had surrendered, while praising those that managed to link up with his unit. Prokopenko, as well as Ukrainian intelligence officer Illia Samoilenko , also blamed Baranyuk for the large losses inflicted on Ukrainian forces, stating his actions were uncoordinated. According to Prokopenko, Baranyuk's breakout attempt was made without warning to other units and the direction of attack was not previously agreed upon, while Samoilenko called Baranyuk a "coward", stating he tried to flee the city, "taking with him people, tanks and ammunition". Ukrainian military expert Oleg Zhdanov claimed that by this point the Russian 810th Guards Naval Infantry Brigade , originally sent from Feodosia , had suffered extremely heavy losses during the siege, to the extent of being "destroyed twice." Ukraine's military stated on 12 March that Russian forces had captured the eastern outskirts of Mariupol. Later, a vehicle convoy of 82 ethnic Greeks was able to leave the city via a humanitarian corridor. On 13 March, Boychenko stated that Russian forces had bombed the city at least 22 times in the previous 24 hours, with a hundred bombs, and added that the last food and water reserves in the city were being depleted. The Ukrainian Ministry of Internal Affairs said that the National Guard of Ukraine had damaged several Russian armored vehicles with artillery strikes during the day. İsmail Hacıoğlu, the head of the local Sultan Suleiman Mosque , stated that 86 Turkish citizens in the city were awaiting evacuation by the Turkish government. More than 160 cars were able to leave the city on 14 March at 13:00 local time, the first evacuation allowed during the siege. The Russian Ministry of Defense stated that 450 tonnes of humanitarian aid had been brought to the city after Russian forces captured the outskirts. Ukrainian military officials were later said to have killed 150 Russian soldiers and destroyed 10 Russian vehicles. On the same day, Ramzan Kadyrov , the head of Chechnya , stated that Chechen soldiers were participating in the siege and had briefly entered Mariupol before retreating. Kadyrov also stated that Adam Delimkhanov , a close ally and member of the State Duma , was the commander of Chechen forces in Mariupol. The funeral for Captain Alexey Glushchak of the GRU was held in Tyumen , and it was revealed he died near Mariupol, likely in the early stages of the siege. On 15 March, around 4,000 vehicles with about 20,000 civilians were able to leave the city. Ukrainian government official Anton Herashchenko said that Russian Major General Oleg Mityaev , commander of the 150th Motorized Rifle Division , was killed when Russian forces tried to storm the city. The Donetsk Regional Drama Theatre , sheltering hundreds of civilians, was hit by a Russian airstrike on 16 March and destroyed. Pavlo Kyrylenko , the governor of Donetsk Oblast, later stated that Russian forces had also targeted the Neptune swimming pool. On 18 March, DPR forces said they had captured the Mariupol airport from Ukrainian forces. Clashes later reached the city center, according to the mayor and on 19 March, Russian and Ukrainian forces began fighting at the Azovstal steel plant. On the same day, President Volodymyr Zelensky awarded Colonel Volodymyr Baranyuk and Major Denys Prokopenko , leaders of the defense in Mariupol, the honor of Hero of Ukraine , the country's highest military award. During this time, while attempting to transport the killed and wounded to the hospital at Azovstal, Major Mykyta Nadtochii, commander of the Azov Regiment's second battalion, was wounded in a Russian airstrike. On 20 March, the city council of Mariupol claimed Russian forces had forcefully deported "several thousand" people to camps and remote cities in Russia over the past week. Russia denied the accusation. The same day, an art school building, which had sheltered some 400 people, was destroyed in a Russian bombing . No information on casualties was immediately available. An order by Russia's Ministry of Defence to surrender, lay down arms and evacuate the city was submitted on 20 March, requesting a written response by 02:00 UTC the next day. The ultimatum was rejected by the Ukrainian government and the mayor of Mariupol. By this point, one of the Ukrainian battalion commanders in the city described "bombs falling every 10 minutes". On 21 March, the first helicopter evacuation from Azovstal took place as eight or nine seriously wounded soldiers were evacuated, including the wounded Major Nadtochii. Two Ukrainian Mil Mi-8 helicopters flew into Azovstal as part of "Operation Air Corridor", carrying a special forces team with crates of Stinger and Javelin missiles, as well as a satellite internet system. "Operation Air Corridor" lasted until 7 April, when one helicopter was shot down, followed by the shooting down of a second helicopter that was sent as part of rescue efforts to search for survivors of the first downing. The four special forces members on board the second helicopter were killed, along with the helicopter's crew. Ukraine claimed 85 seriously wounded soldiers were evacuated as part of "Operation Air Corridor" during seven missions to the Azovstal plant to resupply or deliver reinforcements using some 16 Mi-8s, in pairs or fours, two of which were shot down, along with the rescue helicopter, according to Major General Kyrylo Budanov . In contrast, Ukrainian president Zelensky stated 90 percent of helicopter pilots sent to Mariupol during the course of the siege to resupply Ukrainian forces and evacuate the wounded were lost due to Russian air-defenses. According to Russia, one Ukrainian Mil Mi-8 helicopter was shot down on 28 March, as it was heading to Mariupol to evacuate the leaders of the Azov Regiment. In addition, Russia reported its forces shot down two more Ukrainian Mi-8s on 5 April, as they were once again attempting to evacuate Azov commanders. The Times later reported, after interviewing Ukrainian participants, that from 21 March to 11 May, 15 helicopters and 45 aircrew made nearly 30 attempted rescue missions delivering ammunition, equipment, medicine and evacuating wounded, with 6 flights being successful and 3 helicopters shot down with 23 killed in one crash. On 23 March, local authorities, including the mayor, left the city due to the deteriorating situation. The following day, Russian forces entered central Mariupol, seizing the Orthodox Church of the Intercession of the Mother of God. The city administration alleged that Russians were trying to demoralize residents by publicly shouting claims of Russian victories, including statements that Odesa had been captured. Vadym Boychenko said on 27 March that while Mariupol was still under Ukrainian control, Russian forces had entered deep into the city and that the city's population needed a "complete evacuation". By this point, Ukrainian soldiers had run out of food and clean drinking water, and an analyst believed that Ukrainian forces would not be able to fight on beyond a few days. However, Ukrainian officers refused to evacuate from the city, as they did not want to abandon their wounded and dead soldiers and civilians. The "Club 8bit" computer museum was destroyed. On 28 March, Mayor Vadym Boychenko said "we are in the hands of the occupiers today" in a televised interview, and a spokesman for the Mariupol mayor's office announced that "nearly 5,000 people" had been killed in the city since the start of the siege. The Ukrainian government estimated that "from 20,000 to 30,000" Mariupol residents had been forcibly sent to camps in Russia under Russian military control. During the day, Russian forces seized the administrative building in the northern Kalmiuskyi District and the military headquarters of the Azov Regiment. The next day, Russian forces were reported to have likely divided Ukrainian troops in the city into two and possibly even three pockets. On 2 April, Russian forces captured the SBU building in central Mariupol, after which there was no more reported fighting in the area. On 4 April, one Ukrainian battalion surrendered, with Russian officials stating two days later they captured 267 Ukrainian marines from the 503rd Battalion of the Ukrainian Naval Forces . Due to the surrender, the lines between the Ukrainian 36th Separate Marine Brigade and the Azov Regiment had been broken. On 7 April, the DPR announced central Mariupol had been cleared of Ukrainian forces. Meanwhile, Russian troops started an advance from the southwest on 1 April, leaving the Ukrainian military in partial control of the area around the port in the southwest of Mariupol by 7 April. On 4 April, a Russian Navy missile hit a Malta -based Dominica -flagged cargo ship, resulting in the ship catching fire. In addition, on 7 April, Russian forces captured a bridge leading to the Azovstal steel plant. The following day, Russian troops seized the southern part of Mariupol's port. On 10 April, Russian forces captured the fishing port, separating Ukrainian troops in the port from those in the Azovstal steel plant into two pockets, while a possible third pocket was centered on the Illich steel plant to the north. The next day, DPR forces claimed to have captured 80% of Mariupol. Local Ukrainian forces expected the city to fall soon, since they were running out of ammunition, and analysts at the Institute for the Study of War believed that Mariupol would fall within a week. On 11 April, Russian media reported that 160 Ukrainian servicemen from the 36th Separate Marine Brigade were captured with their equipment. During the night between 11 and 12 April, Baranyuk led the 36th Separate Marine Brigade in an attempt to break out of the Russian encirclement at the Illich steel plant to the north. After being spotted they broke into smaller groups, with some of them managing to link up with fighters of the Azov Regiment at the Azovstal plant to the southeast. A large number of Ukrainian servicemen were either killed or captured during the breakout. The fate of Baranyuk initially remained unknown. Later, the DPR claimed that they had identified the body of Baranyuk after their special forces blocked the Ukrainian breakout. However, on 8 May, Baranyuk appeared alive in an interview with RT , along with the 36th Brigade's Chief of Staff Dmytro Kormiankov. They were reported to have been captured during the breakout attempt. Around the same time at 11 April, a 16-man detachment from a battalion of tankers of the 17th Tank Brigade , which were doing operations supporting the 36th Brigade, did not follow Baranyuk's plan and instead broke through the siege. They used two tanks, anti-aircraft guns and cars for transport, and after breaking out they proceeded on foot for 175 km until reaching friendly Ukrainian positions. For leading his men to safety, the unit's commander, Lieutenant Colonel Oleg Grudzevych, was awarded a Hero of Ukraine medal. On 12 April, Aiden Aslin , a British man fighting with the Ukrainian Marines, reported that his unit was going to surrender since they had run out of ammunition, food and other supplies. Subsequently, in the evening, Russia stated that 1,026 Marines of the 36th Separate Marine Brigade had surrendered at the Illich steel plant, including 162 officers and 400 wounded fighters. Later, Russia said it captured an additional 134 Ukrainian servicemen, bringing the total number of prisoners to 1,160. Ukraine confirmed nearly 1,000 Marines had been captured, including wounded and those who remained at the Illich plant. On 13 April, Russian forces secured the Illich plant, reducing the number of pockets in Mariupol to two, while Russia also announced it had taken full control of Mariupol's commercial port, which was confirmed three days later. The commander of the Azov Regiment, Prokopenko, criticized the servicemen that had surrendered, while praising those that managed to link up with his unit. Prokopenko, as well as Ukrainian intelligence officer Illia Samoilenko , also blamed Baranyuk for the large losses inflicted on Ukrainian forces, stating his actions were uncoordinated. According to Prokopenko, Baranyuk's breakout attempt was made without warning to other units and the direction of attack was not previously agreed upon, while Samoilenko called Baranyuk a "coward", stating he tried to flee the city, "taking with him people, tanks and ammunition". Ukrainian military expert Oleg Zhdanov claimed that by this point the Russian 810th Guards Naval Infantry Brigade , originally sent from Feodosia , had suffered extremely heavy losses during the siege, to the extent of being "destroyed twice." On 15 April, a Ukrainian military commander issued a plea for military reinforcements to come and "break the siege" of Mariupol. He also said that "the situation is critical and the fighting is fierce" but that sending reinforcements and breaking the siege "can be done and it must be done as soon as possible". On the same day, Ukrainian Defence Ministry spokesman Oleksandr Motuzianyk reported Russia started using Tu-22M3 long-range bombers to strike targets in Mariupol. The Azovstal iron and steel works , the heart of one of the remaining pockets of resistance, was well-defended and described as a "fortress within a city", as the steel plant was an enormous complex that made locating the Ukrainian forces difficult and had workshops that were difficult to destroy from the air. Additionally, the complex contained a system of underground tunnels, which would make clearing the entire complex challenging. During the day, Russian forces captured the base of the Ukrainian National Guard's 12th Operational Brigade [ ru ; uk ] , in western Mariupol. On 16 April, DPR troops seized a police station near Mariupol's beach and Russian forces were confirmed to have seized the Vessel Traffic Control Center at the port. Several days after the port was captured, on 20 April, a Ukrainian Marine officer claimed Marine and Azov forces from the Azovstal plant conducted an evacuation operation of around 500 members of the Ukrainian Border Guard and National Police from the port, as they were running out of ammunition. According to the officer, the Ukrainian forces from the Azovstal pocket made an armoured breakthrough to the port and provided covering fire, as the 500 besieged soldiers retreated to the Azovstal plant. Subsequently, Russia announced all urban areas of the city had been cleared, claiming that Ukrainian forces only remained at the Azovstal Steel Plant. However, fighting was reported to be continuing near Flotskaya street in the western Primorsky District . On 18 April, it was estimated that 95% of the city had been destroyed in the fighting. Ukrainian soldiers ignored a Russian ultimatum to surrender, deciding to fight to the end. Russia threatened to "destroy" those who continued to fight on. A military expert estimated that there could still be 500 to 800 Ukrainian soldiers holding out within the city, while Russian officials estimated that 2,500 Ukrainian soldiers and 400 foreign volunteers were holding out within the Azovstal plant. On 20 April, Russian and DPR forces made small advances on the outskirts of the Azovstal plant. That same day, Ukraine accused Russia of bombing a hospital sheltering 300 people. Serhiy Taruta , the former governor of the Donetsk region and a Mariupol native, said 300 people, including wounded troops and civilians with children, were sheltered at the hospital. On 21 April, Russian President Vladimir Putin ordered Russian troops not to storm the Azovstal steel plant, but to blockade it instead until the Ukrainian forces there ran out of supplies. He also reported that "The completion of combat work to liberate Mariupol is a success", while a Ukrainian official rebutted Putin's comments, saying that Russia's choice of implementing a blockade over storming the steel plant meant that Russia had admitted their inability to physically capture Mariupol. General Sir Richard Barrons , former commander of the United Kingdom's Joint Forces Command , assessed that the battle for the plant was no longer "really relevant" in regard to the control of the city and its roads, since Russia and Crimea were now connected. In his opinion, defeating Ukrainian forces at the plant would have been "really difficult" for Russian troops without an "enormous cost to both sides". Despite the ordered blockade, Russian forces advanced within 20 metres (66 ft) of some of the Ukrainian positions. On 22 April, the western Primorsky District was thought to be cleared by Russian forces, with no more reports of fighting, with all of the remaining Ukrainian forces surrounded in the Azovstal Steel Plant. Hundreds of civilians had also taken refuge at the plant. On 23 April, according to Ukraine, airstrikes and an apparent ground assault recommenced on the Azovstal steel works. An advisor to the Ukrainian President said: "The enemy is trying to strangle the final resistance of the defenders of Mariupol in the Azovstal area". However, this could not be independently confirmed. Ukrainian security chief Oleksiy Danilov claimed that at night, a helicopter had resupplied Azovstal. On the same day, it was reported that Russia was redeploying forces from Mariupol to other fronts in eastern Ukraine, with Russia reportedly redeploying 12 units from Mariupol. On the next day, Russian forces continued bombing Ukrainian positions in the Azovstal Steel Plant, with reports that Russian forces might have been planning a renewed assault on the facility. Meanwhile, Ukrainian supplies of ammunition were dwindling, while food and water were running dangerously low. During the night of 27 to 28 April, the heaviest airstrikes yet were reportedly conducted against Azovstal, with more than 50 strikes by Tu-22M3 , Su-25s and Su-24s aircraft hitting the facility, according to Ukraine. Ukraine claimed a military field hospital was hit, with the number of wounded increasing from 170 before the strike to more than 600 after the bombing. On 30 April, the United Nations and the International Committee of the Red Cross (ICRC) started to run evacuations through a humanitarian corridor . This corridor was made after a trip by Secretary-General of the United Nations António Guterres to Moscow the previous week, where he personally brokered a deal. On 30 April, 20 civilians had left the Azovstal steel plant, while Russian media claimed a number of 25. Talks were underway to try and release the remaining 1,000 or so civilians. At least two of the wives of members of the Azov Regiment called for a concurrent evacuation of the about 2,000 forces that would be left behind after the civilian evacuation, highlighting concerns of treatment as POWs by the Russians and lack of medical and food supplies. On 2 May, about 100 civilians were reported to have been evacuated. Russian aircraft, according to the US Department of Defense , were using dumb bombs in Mariupol. Russian ground forces were also reported to be pulling out of the city, possibly to reinforce their positions elsewhere in the Donbas, where Russia was carrying out a large-scale offensive . According to one US DOD official: "Largely the efforts around Mariupol for the Russians are now in the realm of airstrikes". On 3 May, the Russian forces in Mariupol restarted their attacks on Azovstal. They began an assault on the steel plant in what have been called "difficult bloody battles". The following day it was reported the Russians had broken into the plant. Ukrainian politician Davyd Arakhamia said: "Attempts to storm the plant continue for the second day. Russian troops are already on the territory of Azovstal." On 5 May, some 300 civilians were allowed to leave due to Russia opening humanitarian corridors. These corridors ran from 8am to 6pm. Ukrainian forces blamed Russian success on an electrician who gave Russian forces information about the underground tunnel network, claiming: "Yesterday, the Russians started storming these tunnels, using the information they received from the betrayer." On 5 May, The Telegraph reported that Russia had intensified its bombing of the steel factory bunkers by using thermobaric bombs to increase the devastation of deployed firepower against the remaining Ukrainian soldiers who had lost all contact with the Kyiv government; in his last communications, Zelenskyy had authorized the commander of the besieged steel factory to surrender as necessary under the pressure of increased Russian attacks. On 6 May, some 500 civilians, in total, had been evacuated according to the United Nations. The Azov Regiment reported one fighter killed and six wounded while helping evacuate civilians. On 7 May, the Ukrainian government announced that all of the remaining women, children and elderly who had been inside the Azovstal steel plant had been evacuated. On 8 May, the commander of the 36th Separate Marine Brigade, Serhiy Volynskyi , asked "that a higher power find a way to figure out our rescue". As to their current conditions, "It feels like I've landed in a hellish reality show in which us soldiers fight for our lives and the whole world watches this interesting episode. Pain, suffering, hunger, misery, tears, fears, death. It's all real." President Zelenskyy promised "we are working on evacuating our military". On 9 May, the Donetsk People's Republic held a Victory Day parade in Mariupol. The leader of the Republic, Denis Pushilin participated in the event. At the same time, a meeting took place near Mariupol involving Russian military representatives and Ukrainian commanders from Azovstal, including Major Prokopenko, who were brought to the meeting place by Russian armoured vehicles from Azovstal. During the meeting, the terms of the Ukrainians' surrender were agreed upon. On 10 May, Ukrainian authorities reported that over 1,000 Ukrainian soldiers, hundreds of them wounded, remained trapped inside the Azovstal steelworks. The Institute for the Study of War noted the lack of a Russian ground offensive on 12 May, but noted that Russian forces had likely secured the M14 highway the following day. On 16 May, Alexander Khodakovsky, commander of a DPR brigade stationed near Azovstal, stated that a group of nine soldiers had come out of the plant to negotiate under a white flag. On the same day, the Ukrainian General staff announced that the Mariupol garrison had "fulfilled its combat mission" and that "evacuation" from the Azovstal steel plant had begun. The military said that 264 service members, 53 of them seriously wounded, had been taken by bus to areas controlled by Russian forces. A social media post was released by Azov Regiment commander Denys Prokopenko stating: "In order to save lives, the entire Mariupol garrison is implementing the approved decision of the Supreme Military Command and hopes for the support of the Ukrainian people." Wounded Ukrainian soldiers from the Azovstal plant were taken to the DPR -controlled town of Novoazovsk for treatment. The evacuation of wounded troops was followed in the subsequent days by the surrender of the remainder of the garrison. Ukrainian Deputy Defence Minister Hanna Maliar said: "Thanks to the defenders of Mariupol, Ukraine gained critically important time to form reserves and regroup forces and receive help from partners. And they fulfilled all their tasks. But it is impossible to unblock Azovstal by military means." Russia press secretary Dmitry Peskov said Russian President Vladimir Putin had guaranteed that the fighters who surrendered would be treated "in accordance with international standards" while Ukrainian President Volodymyr Zelenskyy said in an address that "the work of bringing the boys home continues, and this work needs delicacy – and time". Some prominent Russian lawmakers called on the government to deny prisoner exchanges for members of the Azov Regiment . The ICRC registered the surrendered troops as prisoners of war at the request of both sides, collecting information to contact their families. On 18 May, Russian artillery and aircraft bombed once again Azovstal's remaining defenders. The DPR leadership claimed that the local high-ranking Ukrainian commanders had not yet surrendered. According to Russian sources, the last defenders surrendered on 20 May, among them Lieutenant Colonel Prokopenko, Major Volynskyi and Captain Svyatoslav Palamar , deputy commander of the Azov Regiment. The Russian Ministry of Defense claimed that altogether 2,439 prisoners had been taken at Azovstal between 16 and 20 May, and that the steel plant was now under control of Russian and DPR forces. On 15 April, a Ukrainian military commander issued a plea for military reinforcements to come and "break the siege" of Mariupol. He also said that "the situation is critical and the fighting is fierce" but that sending reinforcements and breaking the siege "can be done and it must be done as soon as possible". On the same day, Ukrainian Defence Ministry spokesman Oleksandr Motuzianyk reported Russia started using Tu-22M3 long-range bombers to strike targets in Mariupol. The Azovstal iron and steel works , the heart of one of the remaining pockets of resistance, was well-defended and described as a "fortress within a city", as the steel plant was an enormous complex that made locating the Ukrainian forces difficult and had workshops that were difficult to destroy from the air. Additionally, the complex contained a system of underground tunnels, which would make clearing the entire complex challenging. During the day, Russian forces captured the base of the Ukrainian National Guard's 12th Operational Brigade [ ru ; uk ] , in western Mariupol. On 16 April, DPR troops seized a police station near Mariupol's beach and Russian forces were confirmed to have seized the Vessel Traffic Control Center at the port. Several days after the port was captured, on 20 April, a Ukrainian Marine officer claimed Marine and Azov forces from the Azovstal plant conducted an evacuation operation of around 500 members of the Ukrainian Border Guard and National Police from the port, as they were running out of ammunition. According to the officer, the Ukrainian forces from the Azovstal pocket made an armoured breakthrough to the port and provided covering fire, as the 500 besieged soldiers retreated to the Azovstal plant. Subsequently, Russia announced all urban areas of the city had been cleared, claiming that Ukrainian forces only remained at the Azovstal Steel Plant. However, fighting was reported to be continuing near Flotskaya street in the western Primorsky District . On 18 April, it was estimated that 95% of the city had been destroyed in the fighting. Ukrainian soldiers ignored a Russian ultimatum to surrender, deciding to fight to the end. Russia threatened to "destroy" those who continued to fight on. A military expert estimated that there could still be 500 to 800 Ukrainian soldiers holding out within the city, while Russian officials estimated that 2,500 Ukrainian soldiers and 400 foreign volunteers were holding out within the Azovstal plant. On 20 April, Russian and DPR forces made small advances on the outskirts of the Azovstal plant. That same day, Ukraine accused Russia of bombing a hospital sheltering 300 people. Serhiy Taruta , the former governor of the Donetsk region and a Mariupol native, said 300 people, including wounded troops and civilians with children, were sheltered at the hospital. On 21 April, Russian President Vladimir Putin ordered Russian troops not to storm the Azovstal steel plant, but to blockade it instead until the Ukrainian forces there ran out of supplies. He also reported that "The completion of combat work to liberate Mariupol is a success", while a Ukrainian official rebutted Putin's comments, saying that Russia's choice of implementing a blockade over storming the steel plant meant that Russia had admitted their inability to physically capture Mariupol. General Sir Richard Barrons , former commander of the United Kingdom's Joint Forces Command , assessed that the battle for the plant was no longer "really relevant" in regard to the control of the city and its roads, since Russia and Crimea were now connected. In his opinion, defeating Ukrainian forces at the plant would have been "really difficult" for Russian troops without an "enormous cost to both sides". Despite the ordered blockade, Russian forces advanced within 20 metres (66 ft) of some of the Ukrainian positions. On 22 April, the western Primorsky District was thought to be cleared by Russian forces, with no more reports of fighting, with all of the remaining Ukrainian forces surrounded in the Azovstal Steel Plant. Hundreds of civilians had also taken refuge at the plant. On 23 April, according to Ukraine, airstrikes and an apparent ground assault recommenced on the Azovstal steel works. An advisor to the Ukrainian President said: "The enemy is trying to strangle the final resistance of the defenders of Mariupol in the Azovstal area". However, this could not be independently confirmed. Ukrainian security chief Oleksiy Danilov claimed that at night, a helicopter had resupplied Azovstal. On the same day, it was reported that Russia was redeploying forces from Mariupol to other fronts in eastern Ukraine, with Russia reportedly redeploying 12 units from Mariupol. On the next day, Russian forces continued bombing Ukrainian positions in the Azovstal Steel Plant, with reports that Russian forces might have been planning a renewed assault on the facility. Meanwhile, Ukrainian supplies of ammunition were dwindling, while food and water were running dangerously low. During the night of 27 to 28 April, the heaviest airstrikes yet were reportedly conducted against Azovstal, with more than 50 strikes by Tu-22M3 , Su-25s and Su-24s aircraft hitting the facility, according to Ukraine. Ukraine claimed a military field hospital was hit, with the number of wounded increasing from 170 before the strike to more than 600 after the bombing. On 30 April, the United Nations and the International Committee of the Red Cross (ICRC) started to run evacuations through a humanitarian corridor . This corridor was made after a trip by Secretary-General of the United Nations António Guterres to Moscow the previous week, where he personally brokered a deal. On 30 April, 20 civilians had left the Azovstal steel plant, while Russian media claimed a number of 25. Talks were underway to try and release the remaining 1,000 or so civilians. At least two of the wives of members of the Azov Regiment called for a concurrent evacuation of the about 2,000 forces that would be left behind after the civilian evacuation, highlighting concerns of treatment as POWs by the Russians and lack of medical and food supplies. On 2 May, about 100 civilians were reported to have been evacuated. Russian aircraft, according to the US Department of Defense , were using dumb bombs in Mariupol. Russian ground forces were also reported to be pulling out of the city, possibly to reinforce their positions elsewhere in the Donbas, where Russia was carrying out a large-scale offensive . According to one US DOD official: "Largely the efforts around Mariupol for the Russians are now in the realm of airstrikes". On 3 May, the Russian forces in Mariupol restarted their attacks on Azovstal. They began an assault on the steel plant in what have been called "difficult bloody battles". The following day it was reported the Russians had broken into the plant. Ukrainian politician Davyd Arakhamia said: "Attempts to storm the plant continue for the second day. Russian troops are already on the territory of Azovstal." On 5 May, some 300 civilians were allowed to leave due to Russia opening humanitarian corridors. These corridors ran from 8am to 6pm. Ukrainian forces blamed Russian success on an electrician who gave Russian forces information about the underground tunnel network, claiming: "Yesterday, the Russians started storming these tunnels, using the information they received from the betrayer." On 5 May, The Telegraph reported that Russia had intensified its bombing of the steel factory bunkers by using thermobaric bombs to increase the devastation of deployed firepower against the remaining Ukrainian soldiers who had lost all contact with the Kyiv government; in his last communications, Zelenskyy had authorized the commander of the besieged steel factory to surrender as necessary under the pressure of increased Russian attacks. On 6 May, some 500 civilians, in total, had been evacuated according to the United Nations. The Azov Regiment reported one fighter killed and six wounded while helping evacuate civilians. On 7 May, the Ukrainian government announced that all of the remaining women, children and elderly who had been inside the Azovstal steel plant had been evacuated. On 8 May, the commander of the 36th Separate Marine Brigade, Serhiy Volynskyi , asked "that a higher power find a way to figure out our rescue". As to their current conditions, "It feels like I've landed in a hellish reality show in which us soldiers fight for our lives and the whole world watches this interesting episode. Pain, suffering, hunger, misery, tears, fears, death. It's all real." President Zelenskyy promised "we are working on evacuating our military". On 9 May, the Donetsk People's Republic held a Victory Day parade in Mariupol. The leader of the Republic, Denis Pushilin participated in the event. At the same time, a meeting took place near Mariupol involving Russian military representatives and Ukrainian commanders from Azovstal, including Major Prokopenko, who were brought to the meeting place by Russian armoured vehicles from Azovstal. During the meeting, the terms of the Ukrainians' surrender were agreed upon. On 10 May, Ukrainian authorities reported that over 1,000 Ukrainian soldiers, hundreds of them wounded, remained trapped inside the Azovstal steelworks. The Institute for the Study of War noted the lack of a Russian ground offensive on 12 May, but noted that Russian forces had likely secured the M14 highway the following day. On 16 May, Alexander Khodakovsky, commander of a DPR brigade stationed near Azovstal, stated that a group of nine soldiers had come out of the plant to negotiate under a white flag. On the same day, the Ukrainian General staff announced that the Mariupol garrison had "fulfilled its combat mission" and that "evacuation" from the Azovstal steel plant had begun. The military said that 264 service members, 53 of them seriously wounded, had been taken by bus to areas controlled by Russian forces. A social media post was released by Azov Regiment commander Denys Prokopenko stating: "In order to save lives, the entire Mariupol garrison is implementing the approved decision of the Supreme Military Command and hopes for the support of the Ukrainian people." Wounded Ukrainian soldiers from the Azovstal plant were taken to the DPR -controlled town of Novoazovsk for treatment. The evacuation of wounded troops was followed in the subsequent days by the surrender of the remainder of the garrison. Ukrainian Deputy Defence Minister Hanna Maliar said: "Thanks to the defenders of Mariupol, Ukraine gained critically important time to form reserves and regroup forces and receive help from partners. And they fulfilled all their tasks. But it is impossible to unblock Azovstal by military means." Russia press secretary Dmitry Peskov said Russian President Vladimir Putin had guaranteed that the fighters who surrendered would be treated "in accordance with international standards" while Ukrainian President Volodymyr Zelenskyy said in an address that "the work of bringing the boys home continues, and this work needs delicacy – and time". Some prominent Russian lawmakers called on the government to deny prisoner exchanges for members of the Azov Regiment . The ICRC registered the surrendered troops as prisoners of war at the request of both sides, collecting information to contact their families. On 18 May, Russian artillery and aircraft bombed once again Azovstal's remaining defenders. The DPR leadership claimed that the local high-ranking Ukrainian commanders had not yet surrendered. According to Russian sources, the last defenders surrendered on 20 May, among them Lieutenant Colonel Prokopenko, Major Volynskyi and Captain Svyatoslav Palamar , deputy commander of the Azov Regiment. The Russian Ministry of Defense claimed that altogether 2,439 prisoners had been taken at Azovstal between 16 and 20 May, and that the steel plant was now under control of Russian and DPR forces. On 18 May, Denis Pushilin announced Azovstal would be demolished by the Donetsk People's Republic , and Mariupol would be turned into a resort city. On 26 May, Russia reopened the Port of Mariupol to commercial vessels following mine removal. In the months after taking control of the city, Russian authorities had many damaged buildings torn down, sometimes even turning out the remaining residents. Some new houses were also built. Associated Press describes this ongoing process as an effort to "eradicat[e] all vestiges of Ukraine" and to cover up "the evidence of war crimes". Local schools started using the Russian curriculum, the television and radio broadcast in Russian and many street names were replaced by their Soviet-era ones. Russian Telegram bloggers shared a video, reportedly showing Russian soldiers attacking some remaining Ukrainian holdouts at Azovstal on 22 May. Head of the DPR Denis Pushilin claimed that some Ukrainian holdouts had been discovered and captured in the area of the Azovstal plant. In an explosion at Olenivka prison on 29 July 2022, 53 Ukrainian prisoners of war from Mariupol were killed and 75 wounded. Both Ukrainian and Russian authorities accused each other of the attack on the prison. As of 30 July, there was no independent confirmation of what occurred. On 21 September 2022, 215 Ukrainian prisoners of war from Mariupol were released in a prisoner swap. Under the agreement, Ukrainian Azov Regiment Commander Denys Prokopenko and four other top Ukrainian commanders from the Azovstal siege will be required to stay in Turkey until the end of the war. Mariupol's Mayor Vadym Boychenko had forced to leave Mariupol on February 27 after Ukrainian special services insistence. The information was received from the special services about the intentions of Russian sabotage groups to capture the legitimate mayor. First Deputy Mayor Mykhailo Kohut remained in Mariupol, on Boychenko's behalf, who was responsible for the direction of communal work and city defense. According to the head of the patrol police of Mariupol Mykhailo Vershinin, Kohut helped with the defense of the city from Russian invaders and coordinated public utilities actions under intense shelling. Kohut held his last meeting with public utilities on March 19, at that time street fighting was going on in the city. The last head of public services left the captured city on March 24. The Ukrainian parliament stated on 30 April 2022 that the city's living conditions had been reduced to "medieval" levels, and that most of the city's sanitary and health infrastructure was destroyed, potentially putting the city's citizens at risk of disease. In late April, the Mariupol City Council urged the evacuation of 100,000 residents, warning of "deadly epidemics" in the city. On 28 April 2022, the Rospotrebnadzor issued a 40-paragraph resolution calling for additional measures to be taken in regards to drinking and waste water, especially in places which had become locations for Ukrainian refugees (specifically Belgorod , Bryansk , Kursk , Rostov and Voronezh Oblasts ), as well as providing information to citizens about cholera by 1 June 2022. The government of Rostov Oblast announced that Ukrainian refugees in Russia would be tested for cholera. On 17 May 2022, the World Health Organization warned of the possibility of cholera outbreaks in Ukraine, with WHO Regional Director for Europe Hans Kluge saying, "We are concerned about the potential cholera outbreak in occupied areas where water and sanitation infrastructure is damaged or destroyed." Such concerns were echoed by WHO Ukraine incident Manager Dorit Nitzan, who reported "swamps" of waste water on the streets of Mariupol, and claimed that there were cases of sewage and drinking water being mixed in the city. On 6 June 2022, Ukrainian Deputy Minister of Healthcare Ihor Kuzin warned against a potential cholera outbreak in the city; saying that all preconditions for an outbreak were already present. In addition to Mariupol, Ukrainian task forces tested soil and drinking water in Kyiv , Zhytomyr , Chernihiv , and Sumy Oblasts . Shortly after his announcement, Russian occupational authorities imposed a quarantine on the city. Mayor Boychenko said on 11 June that there was an outbreak of cholera in the city as sanitation systems were broken and corpses were rotting in the streets. Medical officials in Ukraine and Russia have cautioned that cholera could spread beyond Mariupol, with Russian government officials in oblasts bordering Ukraine establishing labs to treat cholera. Ukrainian epidemiologist Liudmyla Mukharska warned that the outbreak could spread throughout the rest of the Donbas , and that outbreaks of intestinal infections, dysentery , salmonellosis , and hepatitis A and E were possible. Other epidemiologists said that due to rotations of Russian soldiers fighting in Ukraine and the deportation of Ukrainians to filtration camps within Russia, the spread of the cholera outbreak to Russia was inevitable. In May 2023, the Ukrainian military began launching long-range missile strikes on Russian positions in Mariupol, who had started to turn the city and the surrounding villages into a military-logistics hub. On 26 May, the Ukrainians claimed that they had killed 250 Russian soldiers in a strike on the Azovstal Steelworks, with another 200 killed the previous week. On 29 May, the Ukrainians claimed to have again struck Mariupol, this time hitting the Yalta Health Center, with 650 Russian soldiers claimed to have been housed there. They claimed to have killed 100 Russians and wounded over 400 in the attack. On 18 May, Denis Pushilin announced Azovstal would be demolished by the Donetsk People's Republic , and Mariupol would be turned into a resort city. On 26 May, Russia reopened the Port of Mariupol to commercial vessels following mine removal. In the months after taking control of the city, Russian authorities had many damaged buildings torn down, sometimes even turning out the remaining residents. Some new houses were also built. Associated Press describes this ongoing process as an effort to "eradicat[e] all vestiges of Ukraine" and to cover up "the evidence of war crimes". Local schools started using the Russian curriculum, the television and radio broadcast in Russian and many street names were replaced by their Soviet-era ones. Russian Telegram bloggers shared a video, reportedly showing Russian soldiers attacking some remaining Ukrainian holdouts at Azovstal on 22 May. Head of the DPR Denis Pushilin claimed that some Ukrainian holdouts had been discovered and captured in the area of the Azovstal plant. In an explosion at Olenivka prison on 29 July 2022, 53 Ukrainian prisoners of war from Mariupol were killed and 75 wounded. Both Ukrainian and Russian authorities accused each other of the attack on the prison. As of 30 July, there was no independent confirmation of what occurred. On 21 September 2022, 215 Ukrainian prisoners of war from Mariupol were released in a prisoner swap. Under the agreement, Ukrainian Azov Regiment Commander Denys Prokopenko and four other top Ukrainian commanders from the Azovstal siege will be required to stay in Turkey until the end of the war. Mariupol's Mayor Vadym Boychenko had forced to leave Mariupol on February 27 after Ukrainian special services insistence. The information was received from the special services about the intentions of Russian sabotage groups to capture the legitimate mayor. First Deputy Mayor Mykhailo Kohut remained in Mariupol, on Boychenko's behalf, who was responsible for the direction of communal work and city defense. According to the head of the patrol police of Mariupol Mykhailo Vershinin, Kohut helped with the defense of the city from Russian invaders and coordinated public utilities actions under intense shelling. Kohut held his last meeting with public utilities on March 19, at that time street fighting was going on in the city. The last head of public services left the captured city on March 24. The Ukrainian parliament stated on 30 April 2022 that the city's living conditions had been reduced to "medieval" levels, and that most of the city's sanitary and health infrastructure was destroyed, potentially putting the city's citizens at risk of disease. In late April, the Mariupol City Council urged the evacuation of 100,000 residents, warning of "deadly epidemics" in the city. On 28 April 2022, the Rospotrebnadzor issued a 40-paragraph resolution calling for additional measures to be taken in regards to drinking and waste water, especially in places which had become locations for Ukrainian refugees (specifically Belgorod , Bryansk , Kursk , Rostov and Voronezh Oblasts ), as well as providing information to citizens about cholera by 1 June 2022. The government of Rostov Oblast announced that Ukrainian refugees in Russia would be tested for cholera. On 17 May 2022, the World Health Organization warned of the possibility of cholera outbreaks in Ukraine, with WHO Regional Director for Europe Hans Kluge saying, "We are concerned about the potential cholera outbreak in occupied areas where water and sanitation infrastructure is damaged or destroyed." Such concerns were echoed by WHO Ukraine incident Manager Dorit Nitzan, who reported "swamps" of waste water on the streets of Mariupol, and claimed that there were cases of sewage and drinking water being mixed in the city. On 6 June 2022, Ukrainian Deputy Minister of Healthcare Ihor Kuzin warned against a potential cholera outbreak in the city; saying that all preconditions for an outbreak were already present. In addition to Mariupol, Ukrainian task forces tested soil and drinking water in Kyiv , Zhytomyr , Chernihiv , and Sumy Oblasts . Shortly after his announcement, Russian occupational authorities imposed a quarantine on the city. Mayor Boychenko said on 11 June that there was an outbreak of cholera in the city as sanitation systems were broken and corpses were rotting in the streets. Medical officials in Ukraine and Russia have cautioned that cholera could spread beyond Mariupol, with Russian government officials in oblasts bordering Ukraine establishing labs to treat cholera. Ukrainian epidemiologist Liudmyla Mukharska warned that the outbreak could spread throughout the rest of the Donbas , and that outbreaks of intestinal infections, dysentery , salmonellosis , and hepatitis A and E were possible. Other epidemiologists said that due to rotations of Russian soldiers fighting in Ukraine and the deportation of Ukrainians to filtration camps within Russia, the spread of the cholera outbreak to Russia was inevitable. In May 2023, the Ukrainian military began launching long-range missile strikes on Russian positions in Mariupol, who had started to turn the city and the surrounding villages into a military-logistics hub. On 26 May, the Ukrainians claimed that they had killed 250 Russian soldiers in a strike on the Azovstal Steelworks, with another 200 killed the previous week. On 29 May, the Ukrainians claimed to have again struck Mariupol, this time hitting the Yalta Health Center, with 650 Russian soldiers claimed to have been housed there. They claimed to have killed 100 Russians and wounded over 400 in the attack. Russia said more than 4,000 Ukrainian soldiers had died up to the start of the siege of the Azovstal plant in mid-April and that the bodies of another 152 Ukrainian soldiers were found in a non-functioning refrigerated truck in Azovstal following the facility's siege. Explosives capable of destroying the bodies were found underneath them. The bodies would be handed over to Ukraine. By 12 June, Russia returned the bodies of some 220 deceased Ukrainian soldiers, all of whom had been fighting in the Azovstal steelworks, while "just as many bodies" still remained in Mariupol. A third of these were soldiers from the Azov unit. Subsequently, another 145 bodies of those killed in Mariupol were returned. As of March 2024, Ukrainian obituaries recorded the names of 798 Ukrainian servicemen killed during the siege. According to Ukraine, around 6,500 Russian soldiers were killed during the siege, with about four thousand of them being from only "one of three directions of attack on Mariupol". They also said the 810th Naval Infantry Brigade of Russia's Black Sea Fleet had 158 killed, 500 wounded and 70 missing by mid-April, while the Black Sea Fleet's 126th Coastal Defence Brigade , a unit of about 2,000 soldiers, suffered 75 percent losses. In addition, Ukraine claimed 14 special forces members of the Russian Spetsnaz GRU were killed by late March. According to Russia, some 3,917 Ukrainian soldiers were captured during the siege, [lower-alpha 4] while Ukraine confirmed more than 3,500 soldiers, with an additional battalion, were taken prisoner. Around 700 of these were members of the Azov Battalion. On 8 June, over 1,000 prisoners of war were transferred from the DPR to Russia. Mariupol's deputy mayor Serhiy Orlov stated on 9 March that at least 1,170 civilians in the city had been killed in the city since Russia's invasion began and the dead were being buried in mass graves. On 11 March, the city council stated that at least 1,582 civilians had been killed during the siege, increasing that number on 13 March to 2,187 having been killed by the latter date. On 14 March, Oleksiy Arestovych , an adviser to Ukrainian president Volodymyr Zelenskyy , stated that more than 2,500 civilians had been killed in Mariupol's siege. However, the city council later clarified that 2,357 civilians had died. Pyotr Andryushchenko, an adviser to the city government, however stated that the council's count was inaccurate and estimated that total number of civilians killed could be as high as 20,000. The New York Times reported that officials in the city had been struggling to account for how many civilians had died or gone missing during the siege. Videos posted on Telegram showed that residents of the Cheremushky neighborhood were forced to bury corpses in a courtyard, while others had to turn a post office building into a makeshift morgue, stacking it with dead bodies. On 16 March, the Associated Press (AP) reported that it had documented that many of the dead were "children and mothers" contrary, it said, to Russian government claims that civilians had not been targeted. It also reported that doctors in Mariupol were saying that they were treating "10 injured civilians for every injured Ukrainian soldier." On 11 April, Mariupol Mayor Vadym Boychenko stated that over 10,000 civilians had died in the Russian siege of Mariupol. On 12 April, city officials reported that up to 20,000 civilians had been killed. On the same day, the Mayor of the city reported that about 21,000 civilians had been killed. An updated Ukrainian death toll the following month put the number of civilians killed at at least 22,000. By mid-June, the United Nations stated it had confirmed the deaths of 1,348 civilians, but said the true death toll was "likely thousands higher". On August 29, President of Mariupol Television, volunteer and civil activist Mykola Osychenko said to Dnipro TV that, according to the insider information, 87,000 deaths have been currently documented in morgues in Mariupol. Besides, 26,750 bodies are buried in mass graves, and many more are buried in the yards of the apartment blocks and private houses, or still under the rubble. In early November, Ukraine stated that at least 25,000 civilians had been killed in Mariupol. In late December, based on the discovery of 10,300 new mass graves, the Associated Press estimated that the true death toll may be up to three times that figure. According to a recent study by Human Rights Watch and two other organizations, there were at least 8,034 excess deaths in Mariupol between March 2022 and February 2023. The Greek minority in Ukraine which is concentrated in and around Mariupol was impacted heavily by the fighting. Sartana and Volnovakha , two towns near Mariupol with substantial Greek populations, were hit hard by Russian forces and nearly completely destroyed. Russia said more than 4,000 Ukrainian soldiers had died up to the start of the siege of the Azovstal plant in mid-April and that the bodies of another 152 Ukrainian soldiers were found in a non-functioning refrigerated truck in Azovstal following the facility's siege. Explosives capable of destroying the bodies were found underneath them. The bodies would be handed over to Ukraine. By 12 June, Russia returned the bodies of some 220 deceased Ukrainian soldiers, all of whom had been fighting in the Azovstal steelworks, while "just as many bodies" still remained in Mariupol. A third of these were soldiers from the Azov unit. Subsequently, another 145 bodies of those killed in Mariupol were returned. As of March 2024, Ukrainian obituaries recorded the names of 798 Ukrainian servicemen killed during the siege. According to Ukraine, around 6,500 Russian soldiers were killed during the siege, with about four thousand of them being from only "one of three directions of attack on Mariupol". They also said the 810th Naval Infantry Brigade of Russia's Black Sea Fleet had 158 killed, 500 wounded and 70 missing by mid-April, while the Black Sea Fleet's 126th Coastal Defence Brigade , a unit of about 2,000 soldiers, suffered 75 percent losses. In addition, Ukraine claimed 14 special forces members of the Russian Spetsnaz GRU were killed by late March. According to Russia, some 3,917 Ukrainian soldiers were captured during the siege, [lower-alpha 4] while Ukraine confirmed more than 3,500 soldiers, with an additional battalion, were taken prisoner. Around 700 of these were members of the Azov Battalion. On 8 June, over 1,000 prisoners of war were transferred from the DPR to Russia. Mariupol's deputy mayor Serhiy Orlov stated on 9 March that at least 1,170 civilians in the city had been killed in the city since Russia's invasion began and the dead were being buried in mass graves. On 11 March, the city council stated that at least 1,582 civilians had been killed during the siege, increasing that number on 13 March to 2,187 having been killed by the latter date. On 14 March, Oleksiy Arestovych , an adviser to Ukrainian president Volodymyr Zelenskyy , stated that more than 2,500 civilians had been killed in Mariupol's siege. However, the city council later clarified that 2,357 civilians had died. Pyotr Andryushchenko, an adviser to the city government, however stated that the council's count was inaccurate and estimated that total number of civilians killed could be as high as 20,000. The New York Times reported that officials in the city had been struggling to account for how many civilians had died or gone missing during the siege. Videos posted on Telegram showed that residents of the Cheremushky neighborhood were forced to bury corpses in a courtyard, while others had to turn a post office building into a makeshift morgue, stacking it with dead bodies. On 16 March, the Associated Press (AP) reported that it had documented that many of the dead were "children and mothers" contrary, it said, to Russian government claims that civilians had not been targeted. It also reported that doctors in Mariupol were saying that they were treating "10 injured civilians for every injured Ukrainian soldier." On 11 April, Mariupol Mayor Vadym Boychenko stated that over 10,000 civilians had died in the Russian siege of Mariupol. On 12 April, city officials reported that up to 20,000 civilians had been killed. On the same day, the Mayor of the city reported that about 21,000 civilians had been killed. An updated Ukrainian death toll the following month put the number of civilians killed at at least 22,000. By mid-June, the United Nations stated it had confirmed the deaths of 1,348 civilians, but said the true death toll was "likely thousands higher". On August 29, President of Mariupol Television, volunteer and civil activist Mykola Osychenko said to Dnipro TV that, according to the insider information, 87,000 deaths have been currently documented in morgues in Mariupol. Besides, 26,750 bodies are buried in mass graves, and many more are buried in the yards of the apartment blocks and private houses, or still under the rubble. In early November, Ukraine stated that at least 25,000 civilians had been killed in Mariupol. In late December, based on the discovery of 10,300 new mass graves, the Associated Press estimated that the true death toll may be up to three times that figure. According to a recent study by Human Rights Watch and two other organizations, there were at least 8,034 excess deaths in Mariupol between March 2022 and February 2023. The Greek minority in Ukraine which is concentrated in and around Mariupol was impacted heavily by the fighting. Sartana and Volnovakha , two towns near Mariupol with substantial Greek populations, were hit hard by Russian forces and nearly completely destroyed. On 6 March, Petro Andryushchenko, advisor to the mayor of Mariupol, reported that people were "drinking from puddles in the streets" due to the loss of running water in the city caused by days of around-the-clock Russian shelling and bombing attacks. He also stated that there was no heat, electricity or telephone service. According to US officials, civilians had been unable to evacuate the city due to repeated ceasefire violations, attacks on agreed-upon evacuation corridors, and direct attacks on civilians attempting to evacuate. On 14 March, another spokesman for the ICRC announced that "hundreds of thousands" of people in the city were "facing extreme or total shortages of basic necessities like food, water and medicine." On 15 March, Ukraine's Deputy Prime Minister Iryna Vereshchuk accused Russian forces of taking around 400 civilians hostage after capturing a hospital in the city. Ukrainian officials accused Russian forces of firing at an evacuation convoy and injuring five civilians on 16 March. On 18 March, Ukrainian officials stated that more than 350,000 people were sheltering under siege in Mariupol, still with no access to food or water. On 21 March, CNN reported that an official in Mariupol said that people are afraid, due to the constant bombing and shelling, to leave their underground shelters even to obtain food and water, meaning they were trying to drink less and eat less. On 22 March, CNN reported that the Russian Army had confiscated 11 buses that were headed into the city in order to evacuate citizens. Fox News later reported that at least some of the buses were filled with humanitarian supplies which were taken. It was also reported that 15 aid workers in the buses have been arrested while trying to get food into Mariupol. CNN also reported that to that date, all attempts to bring empty buses into Mariupol to evacuate civilians had failed. On 23 March, Ukrainian President Zelenskeyy announced that 100,000 civilians were still unable to get out of Mariupol and that they were trapped in "inhumane conditions" without food, running water or medicine. On 1 April, a rescue effort by the UN to transport hundreds of civilian survivors out of Mariupol with 50 buses failed. Ultimately the ICRC reported that it had helped facilitate the safe evacuation of over 10,000 civilians from Mariupol and Sumy . Numerous war crimes were committed by Russian forces during the siege. Some media outlets described the crimes that occurred as the worst seen in the 21st century. On 25 March, Russian Colonel-General Mikhail Mizintsev was accused by Ukrainian authorities of ordering the bombings of both the Mariupol Children's and Maternity Hospital and the city theatre where 1,200 civilians were sheltering. Mizintsev was nicknamed the "Butcher of Mariupol" by western and Ukrainian sources as a result of his alleged role in the siege, and sanctioned by the United Kingdom. Accused of personally directing war crimes during the siege, Mizintsev accused Ukrainian troops of creating a "terrible human catastrophe," and furthermore claimed that he would allow the safe exit of Ukrainian civilians from Mariupol. Mizintsev's claims were rejected by Deputy Prime Minister of Ukraine Iryna Vereshchuk as "manipulation." On 7 March, U.S. ambassador to the Organization for Security and Co-operation in Europe , Michael Carpenter , described two incidents that occurred in Mariupol on 5 and 6 March as war crimes. He stated that on both dates, Russian forces bombed agreed-upon evacuation corridors while civilians were trying to use them. On 9 March, after an airstrike damaged a maternity ward and children's hospital, Ukrainian President Volodymyr Zelenskyy tweeted that the attack was an "atrocity" along with a video of the building's ruins. The hospital was destroyed. Three people were killed, including a young girl and at least 16 were injured; authorities stated that many more patients and hospital staff were buried under rubble from the blast. Russian foreign minister Sergey Lavrov said that the building was formerly a maternity hospital, and Russia bombed it because it was then occupied by the Azov Regiment. Later on the same day, Russian Ministry of Foreign Affairs spokeswoman Maria Zakharova rejected the hospital bombing as "information terrorism", while Russian Ministry of Defence spokesman Igor Konashenkov called the bombardment staged. Then, on the afternoon of 10 March, the Russian Embassy to the UK said in a tweet that two injured pregnant women seen being evacuated after the attack were actually played by actresses wearing "realistic make-up", that the maternity ward was occupied by the Azov Regiment and that no women or children had been present since the facility was "non-operational". The tweet was later removed by Twitter for violating their rules on disinformation . Dmitry Peskov , the press secretary for the Russian President, stated soon after the bombing that the Russian government would investigate the incident. The accusation by Russia then began trending online in Russia, including on Russian Telegram social media , which has hundreds of thousands of followers. Twitter then took down the embassy's posts. The pregnant woman videotaped being carried out wounded on a stretcher (accused by Russia of being an actress) was moved to another hospital and then died on 13 March, after her child was stillborn. She had suffered numerous injuries in the bombing, including a crushed pelvis and detached hip, which contributed to the stillbirth of her child. Seeing that she had lost her baby, medical workers said that she cried, "Kill me now." Thirty minutes later, she also died. Russian claims that the videos were faked and that the bombed hospital was being used as a military post were debunked by investigative reporters. On 22 March, Russian journalist Alexander Nevzorov was charged under Russia's "false information" law after he published information about the Russian shelling of a maternity hospital in Mariupol. Under a new law passed on 4 March, he could be sentenced to up to 15 years in prison. [ needs update ] On 16 March, the Donetsk Regional Drama Theatre of the city was struck and largely destroyed by an airstrike. The Mariupol city council accused Russia of targeting the drama theatre, where at least hundreds of civilians had been sheltering. Human Rights Watch stated that the theatre was sheltering at least 500 civilians. Serhiy Taruta , the former governor of Donetsk Oblast, stated that 1,300 were sheltering inside. A satellite image taken by Maxar Technologies on 14 March showed that the Russian word for "children" was written in large white letters on the pavement in both the front and the back of the theatre, which would make it clear that civilians were sheltering inside. Ukrainian Minister of Foreign Affairs Dmytro Kuleba claimed that Russia "could not have not known this was a civilian shelter". According to the Verkhovna Rada , [ clarification needed ] it was impossible to start rescue operations at the theatre due to the ongoing shelling. The city council also stated that access to the shelter in the theatre was blocked by debris. The Russian Defense Ministry denied attacking the building and accused the Azov Regiment of blowing it up. The bomb shelter in the basement, where people had been sheltering, however, was able to resist the attack according to Taruta. Survivors began emerging from the remains of the theatre on 17 March. More than 130 civilians had been rescued from the basement as of 18 March, according to Ukrainian officials, and rescuers had yet to find any fatalities. The city council stated that no one had died according to initial information, but one person was gravely wounded. The Associated Press reported that 600 civilians were killed during the airstrike, double the official number given by the Ukrainian government. On 2 March, deputy mayor Sergiy Orlov reported that Russian artillery targeted a densely populated neighborhood of Mariupol, shelling it for nearly 15 hours. He said that one populated residential district on the city's left bank had been "nearly totally destroyed". Satellite photos of Mariupol taken the morning of 9 March taken by Maxar Technologies showed "extensive damage" to high-rise apartments, residential homes, grocery stores and other civilian infrastructure. This was determined by comparing before and after photos. The Mariupol council made a statement that the damage to the city has been "enormous". It estimated that approximately 80% of the city's homes had been significantly damaged, of which almost 30% were beyond repair. Reporting from Mariupol, Reuters reporter Pavel Klimov said that "all around are the blackened shells" of tower block dwellings. On 16 March, BBC News reported that nearly constant Russian attacks had turned residential neighbourhoods into "a wasteland." On the same day it reported that it had obtained drone footage showing "a vast extent of damage, with fire and smoke billowing out of apartment blocks and blackened streets in ruins." A city resident told the BBC that "in the left bank area, there's no residential building intact, it's all burned to the ground." The left bank contained a densely populated residential district. She also said that the city centre is "unrecognisable." On the same day the Institute for the Study of War (ISW) reported that Russian forces continued to commit war crimes in Mariupol including "targeting civilian infrastructure." On 18 March, Lieutenant General Jim Hockenhull, Chief of Defence Intelligence for the United Kingdom (UK), described "continued targeting of civilians in Mariupol". Ukrainian authorities stated that about 90% of buildings in Mariupol were now damaged or destroyed. On the same day, Sky News from the UK described videos as showing "civilian areas left unrecognisable by the bombing." Sky News also quoted the Red Cross as describing "Apocalyptic destruction in Mariupol." On 19 March 2022, a Ukrainian police officer in Mariupol made a video in which he said "Children, elderly people are dying. The city is destroyed and it is wiped off the face of the earth." The video was authenticated by the Associated Press. The government of Mariupol said on 28 March that 90% of all buildings in Mariupol had been damaged by shelling, with 40% of all structures inside the city destroyed. The statistics released also counted that 90% of Mariupol's hospitals had been damaged, and that 23 schools and 28 kindergartens had been destroyed by Russian shelling. By 18 April, Ukrainian officials estimated that at least 95% of Mariupol had been destroyed in the fighting, largely as a result of the Russian bombing campaigns. On 12 April, city officials reported that up to 20,000 civilians had been killed. On the same day, the Mayor of the city reported that about 21,000 civilians had been killed. On 11 April 2022, Eduard Basurin , a spokesperson for the Donetsk People's Republic , called for Russia to bring "chemical forces" to "smoke out the moles", referring to the Ukrainian forces in the Azovstal. Later on the same day, the Azov Regiment accused Russian forces of using "a poisonous substance of unknown origin" in Mariupol, causing respiratory problems. A Pentagon spokesperson said the reports were not confirmed, but they reflect concerns about Russia's potential use of chemical agents. Later, Ukraine stated that it was investigating the allegations. Three Ukrainian soldiers were injured in the incident. As of 2022, according to experts, it was too soon to say what exactly had happened, UK and Ukrainian officials said that they suspected the use of white phosphorus , which is not typically regarded as a chemical weapon in international law. On 7 March, U.S. ambassador to the Organization for Security and Co-operation in Europe , Michael Carpenter , described two incidents that occurred in Mariupol on 5 and 6 March as war crimes. He stated that on both dates, Russian forces bombed agreed-upon evacuation corridors while civilians were trying to use them. On 9 March, after an airstrike damaged a maternity ward and children's hospital, Ukrainian President Volodymyr Zelenskyy tweeted that the attack was an "atrocity" along with a video of the building's ruins. The hospital was destroyed. Three people were killed, including a young girl and at least 16 were injured; authorities stated that many more patients and hospital staff were buried under rubble from the blast. Russian foreign minister Sergey Lavrov said that the building was formerly a maternity hospital, and Russia bombed it because it was then occupied by the Azov Regiment. Later on the same day, Russian Ministry of Foreign Affairs spokeswoman Maria Zakharova rejected the hospital bombing as "information terrorism", while Russian Ministry of Defence spokesman Igor Konashenkov called the bombardment staged. Then, on the afternoon of 10 March, the Russian Embassy to the UK said in a tweet that two injured pregnant women seen being evacuated after the attack were actually played by actresses wearing "realistic make-up", that the maternity ward was occupied by the Azov Regiment and that no women or children had been present since the facility was "non-operational". The tweet was later removed by Twitter for violating their rules on disinformation . Dmitry Peskov , the press secretary for the Russian President, stated soon after the bombing that the Russian government would investigate the incident. The accusation by Russia then began trending online in Russia, including on Russian Telegram social media , which has hundreds of thousands of followers. Twitter then took down the embassy's posts. The pregnant woman videotaped being carried out wounded on a stretcher (accused by Russia of being an actress) was moved to another hospital and then died on 13 March, after her child was stillborn. She had suffered numerous injuries in the bombing, including a crushed pelvis and detached hip, which contributed to the stillbirth of her child. Seeing that she had lost her baby, medical workers said that she cried, "Kill me now." Thirty minutes later, she also died. Russian claims that the videos were faked and that the bombed hospital was being used as a military post were debunked by investigative reporters. On 22 March, Russian journalist Alexander Nevzorov was charged under Russia's "false information" law after he published information about the Russian shelling of a maternity hospital in Mariupol. Under a new law passed on 4 March, he could be sentenced to up to 15 years in prison. [ needs update ]On 16 March, the Donetsk Regional Drama Theatre of the city was struck and largely destroyed by an airstrike. The Mariupol city council accused Russia of targeting the drama theatre, where at least hundreds of civilians had been sheltering. Human Rights Watch stated that the theatre was sheltering at least 500 civilians. Serhiy Taruta , the former governor of Donetsk Oblast, stated that 1,300 were sheltering inside. A satellite image taken by Maxar Technologies on 14 March showed that the Russian word for "children" was written in large white letters on the pavement in both the front and the back of the theatre, which would make it clear that civilians were sheltering inside. Ukrainian Minister of Foreign Affairs Dmytro Kuleba claimed that Russia "could not have not known this was a civilian shelter". According to the Verkhovna Rada , [ clarification needed ] it was impossible to start rescue operations at the theatre due to the ongoing shelling. The city council also stated that access to the shelter in the theatre was blocked by debris. The Russian Defense Ministry denied attacking the building and accused the Azov Regiment of blowing it up. The bomb shelter in the basement, where people had been sheltering, however, was able to resist the attack according to Taruta. Survivors began emerging from the remains of the theatre on 17 March. More than 130 civilians had been rescued from the basement as of 18 March, according to Ukrainian officials, and rescuers had yet to find any fatalities. The city council stated that no one had died according to initial information, but one person was gravely wounded. The Associated Press reported that 600 civilians were killed during the airstrike, double the official number given by the Ukrainian government.On 2 March, deputy mayor Sergiy Orlov reported that Russian artillery targeted a densely populated neighborhood of Mariupol, shelling it for nearly 15 hours. He said that one populated residential district on the city's left bank had been "nearly totally destroyed". Satellite photos of Mariupol taken the morning of 9 March taken by Maxar Technologies showed "extensive damage" to high-rise apartments, residential homes, grocery stores and other civilian infrastructure. This was determined by comparing before and after photos. The Mariupol council made a statement that the damage to the city has been "enormous". It estimated that approximately 80% of the city's homes had been significantly damaged, of which almost 30% were beyond repair. Reporting from Mariupol, Reuters reporter Pavel Klimov said that "all around are the blackened shells" of tower block dwellings. On 16 March, BBC News reported that nearly constant Russian attacks had turned residential neighbourhoods into "a wasteland." On the same day it reported that it had obtained drone footage showing "a vast extent of damage, with fire and smoke billowing out of apartment blocks and blackened streets in ruins." A city resident told the BBC that "in the left bank area, there's no residential building intact, it's all burned to the ground." The left bank contained a densely populated residential district. She also said that the city centre is "unrecognisable." On the same day the Institute for the Study of War (ISW) reported that Russian forces continued to commit war crimes in Mariupol including "targeting civilian infrastructure." On 18 March, Lieutenant General Jim Hockenhull, Chief of Defence Intelligence for the United Kingdom (UK), described "continued targeting of civilians in Mariupol". Ukrainian authorities stated that about 90% of buildings in Mariupol were now damaged or destroyed. On the same day, Sky News from the UK described videos as showing "civilian areas left unrecognisable by the bombing." Sky News also quoted the Red Cross as describing "Apocalyptic destruction in Mariupol." On 19 March 2022, a Ukrainian police officer in Mariupol made a video in which he said "Children, elderly people are dying. The city is destroyed and it is wiped off the face of the earth." The video was authenticated by the Associated Press. The government of Mariupol said on 28 March that 90% of all buildings in Mariupol had been damaged by shelling, with 40% of all structures inside the city destroyed. The statistics released also counted that 90% of Mariupol's hospitals had been damaged, and that 23 schools and 28 kindergartens had been destroyed by Russian shelling. By 18 April, Ukrainian officials estimated that at least 95% of Mariupol had been destroyed in the fighting, largely as a result of the Russian bombing campaigns. On 12 April, city officials reported that up to 20,000 civilians had been killed. On the same day, the Mayor of the city reported that about 21,000 civilians had been killed. On 11 April 2022, Eduard Basurin , a spokesperson for the Donetsk People's Republic , called for Russia to bring "chemical forces" to "smoke out the moles", referring to the Ukrainian forces in the Azovstal. Later on the same day, the Azov Regiment accused Russian forces of using "a poisonous substance of unknown origin" in Mariupol, causing respiratory problems. A Pentagon spokesperson said the reports were not confirmed, but they reflect concerns about Russia's potential use of chemical agents. Later, Ukraine stated that it was investigating the allegations. Three Ukrainian soldiers were injured in the incident. As of 2022, according to experts, it was too soon to say what exactly had happened, UK and Ukrainian officials said that they suspected the use of white phosphorus , which is not typically regarded as a chemical weapon in international law. Associated Press staff member Mstyslav Chernov and freelancer Evgeniy Maloletka , working for AP, stayed in Mariupol from late February until 11 March. They were among the few journalists, and, according to the AP, the only international journalists in Mariupol during that period, and their photographs were extensively used by Western media to cover the siege and the situation in the city. According to Chernov, on 11 March, they were in a hospital taking photos, when they were evacuated from the city with the assistance of Ukrainian soldiers. They managed to escape from Mariupol unharmed, at which point, he said, no journalists were left in the city. Testimonies from the Azovstal steel plant were made available via the Starlink satellite connections system . Thousands of Ukrainian troops cut off in Mariupol were able to use Starlink to send and publish online photos and videos to the outside world, before they had to surrender in May. Reporting in the state-controlled media in Russia presented the invasion as a liberation mission and accused Ukrainian troops of attacking civilian targets in Mariupol. In March 2023, during a visit to the city by president Putin, Marat Khusnullin assured that Russian forces did not use artillery fire against residential buildings during their advance on Mariupol, while accusing Ukrainian forces of destruction during their retreat. Previously, a number of videos from during the siege, showed Russian tanks firing at residential buildings. On the same day as Putin talked to Khusnullin, Russian Izvestya published an interview with a commander of a Russian 2S4 "Tyulpan" mortar battery who described that their mortars were so powerful that they were able to collapse nine-story multi-apartment blocks specifically during the siege of Mariupol. The Guardian observed in a piece on Mariupol published after the Russian attack on the Mariupol maternity ward that "Entire settlements reduced to rubble, attacks on civilian targets and the bombing of refugee exit routes were all part of Moscow's brutal Syria campaign ", while the Washington Post under the headline "Russia's Ukraine war builds on tactics it used in Syria, experts say" related the effects on the civilian population as "dwindling food supplies. No electricity or water. Russian tanks roaming the streets. Nights punctuated by shelling." Ukrainian officials warned that this battle risked "becoming a second Aleppo ." The Syria Civil Defense team said "They want to empty those cities of their population, so it will be less costly for Russia to take over," and indeed some estimates were that 75% of Mariupol's population had left by 31 March. On 10 March 2024, creators of a documentary film 20 Days in Mariupol were awarded with the Oscar in the category "Best Documentary Feature Film", the first Oscar in Ukraine's history.

Wiki

Cholera

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

Cholera Hospital

Cholera Hospital was established on June 24, 1854, at Franklin Street in New York City . The institution was built to treat cholera patients who were denied admittance to City Hospital in Manhattan during an onset of the disease in the summer of 1854. The Mayor of New York , Jacob Westervelt , and the New York City Commissioners, took control of the building at 105 Franklin Street in anticipation of an eminent cholera epidemic . A few weeks afterward a second hospital for cholera patients was opened at a schoolhouse on Mott Street in Manhattan. A book published by a New York physician in 1835 shows that a hospital called the Duane-Street Cholera Hospital existed in New York as early as 1835, but the relationship between the Duane Street hospital and the Cholera Hospital at Franklin Street is unclear. Of the 696 patients admitted at both sites, there was a high mortality rate , numbering approximately one half of the persons treated. 265 people succumbed at Cholera Hospital (Franklin Street) and 57 died at the Mott Street hospital. 323 patients recovered from the sickness. New York City's population numbered around 600,000 people in 1854. The total number of cholera cases was well below the nearly 5,000 reported in 1849. Dr. Valey and Dr. Gull, who treated New York City cholera patients at this time, reported that cholera was only contagious when persons came in contact with those who are sick already. They believed that the disease was transmitted when people breathed the air which cholera patients exhaled. The physicians recommended an airy environment for those with the illness. Affected people should be kept away from marshes, garbage, and dirty water. They recommended the ill be quarantined at Cholera Hospital. It was selected by the New York City Board of Health to provide the care the doctors desired for their patients. On the evening of July 14, 1854, a meeting of citizens was held in the 5th Ward of Manhattan. Arguments were voiced in opposition to the Franklin Street establishment. People disliked the confining atmosphere, the uncleanliness, and the densely settled surroundings in close proximity to the building at the 105 Franklin address. These factors posed risks during an outbreak of contagious disease . None of the people who attended the gathering wanted to stop attending to the needs of cholera patients. Instead the consensus was for opening hospitals in each ward in New York City. This would expedite the care of infected persons who could be treated immediately following the onset of cholera symptoms. It was falsely reported that Cholera Hospital received patients with smallpox , typhus , and other contagious diseases. There were inaccurate stories of disturbing the peace of the neighborhood caused by the rapping of hammers of workers constructing coffins. The Physician of Cholera Hospital published daily reports of the number of cholera cases received at the Franklin Street facility. An average of twelve new cases per day were being treated in mid July 1854. In late August 1854 New York City Commissioners of Health decided to stop reporting news of cholera infections, so greatly had the frequency of new cases declined in New York City. Visitors to the city were no longer dissuaded from coming and commerce was reestablished as the panic dissipated. Joseph C. Hutchison, M.D., treated people with Asiatic cholera at the Brooklyn, New York Cholera Hospital in 1854. He published an account of his work in the New York Journal of Medicine in 1855. Hutchison administered a simple treatment to alleviate cholera symptoms. Patients were given an emetic of salt and water to stop their vomiting and ease their stomachs. This enabled additional remedies to be given to them. Each received a single grain of calomel every hour. It was sprinkled on the backs of their tongues and washed down with ice water . Salivation was avoided. When stimulants were required, sulphuric ether was used. The amount needed depended upon its effects on the individual. Hot air baths, blistering, and spirits of turpentine ( turpentine ) were utilized externally, when necessary.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2016–2022_Yemen_cholera_outbreak/html

2016–2022 Yemen cholera outbreak

An outbreak of cholera began in Yemen in October 2016. The outbreak peaked in 2017 with over 2,000 reported deaths in that year alone. In 2017 and 2019, war-torn Yemen accounted for 84% and 93% of all cholera cases in the world, with children constituting the majority of reported cases. As of November 2021, there have been more than 2.5 million cases reported, and more than 4,000 people have died in the Yemen cholera outbreak, which the United Nations deemed the worst humanitarian crisis in the world at that time. However, the outbreak has substantially decreased by 2021, with a successful vaccination program implemented and only 5,676 suspected cases with two deaths reported between January 1 and March 6 of 2021. Vulnerable to water-borne diseases before the conflict, 16 months went by before a program of oral vaccines was started. The cholera outbreak was worsened as a result of the ongoing civil war and the Saudi Arabian-led intervention in Yemen against the Houthi movement that began in March 2015. Airstrikes damaged hospital infrastructure , and water supply and sanitation in Yemen were affected by the ongoing conflict. The government of Yemen stopped funding public health in 2016; sanitation workers were not paid by the government, causing garbage to accumulate, and healthcare workers either fled the country or were not paid. The UNICEF and World Health Organization (WHO) executive directors stated: "This deadly cholera outbreak is the direct consequence of two years of heavy conflict. Collapsing health, water and sanitation systems have cut off 14.5 million people from regular access to clean water and sanitation, increasing the ability of the disease to spread. Rising rates of malnutrition have weakened children's health and made them more vulnerable to disease. An estimated 30,000 dedicated local health workers who play the largest role in ending this outbreak have not been paid their salaries for nearly ten months." As of 2017, Yemen had a population of 25 million and was geographically divided into 22 governorates . The Yemeni Civil War is an ongoing conflict that began in 2015 between two factions: the internationally recognized Yemeni government, led by Abdrabbuh Mansur Hadi , and the Houthi armed movement, along with their supporters and allies. Both claim to constitute the official government of Yemen . Houthi forces controlling the capital Sanaʽa , and allied with forces loyal to the former president Ali Abdullah Saleh , have clashed with forces loyal to the government of Abdrabbuh Mansur Hadi, based in Aden . A Saudi Arabian-led intervention in Yemen was launched in 2015, with Saudi Arabia leading a coalition of nine countries from the Middle East and Africa, in response to calls from President Abdrabbuh Mansur Hadi for military support. Cholera is an infection of the small intestine by strains of the bacterium Vibrio cholerae . It is spread mostly by unsafe water and unsafe food that has been contaminated with human feces containing the bacteria. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Diarrhea can be so severe that it leads, within hours, to severe dehydration and electrolyte imbalance . Vomiting and muscle cramps may also occur. The primary treatment is oral rehydration therapy —the replacement of fluids with slightly sweet and salty solutions . In severe cases, intravenous fluids may be required, and antibiotics may be beneficial. Prevention methods against cholera include improved sanitation and access to clean water . Cholera vaccines that are given by mouth provide reasonable protection for about six months. Two oral killed vaccines are available: Dukoral and Shanchol . Total cost, including delivery costs, of oral cholera vaccination is under US$10 per person. Following "on the heels of civil conflict between Houthi rebels and the internationally recognized Yemeni regime", the Yemen cholera outbreak began in early October 2016, and by January 2017, the WHO Regional Office for the Eastern Mediterranean (WHO EMRO) considered the outbreak to be unusual in its rapid and wide geographical spread. The serotype of vibrio cholerae O1 involved is Ougawa. The earliest cases were predominantly in the capital, Sana'a , with some occurring in Aden . By the end of October, cases had been reported in the governorates of Al-Bayda , Aden, Al-Hudaydah , Hajjah , Ibb , Lahij and Taiz and, by late November, also in Al-Dhale'a and Amran . By mid-December, 135 districts of 15 governorates had reported suspected cases, but nearly two-thirds were confined to Aden, Al-Bayda, Al-Hudaydah and Taiz. By mid-January 2017, 80% of cases were located in 28 districts of Al-Dhale'a, Al-Hudaydah, Hajjah, Lahij and Taiz. A total of 268 districts from 20 governorates had reported cases by 21 June 2017; over half are from the governorates of Amanat Al Asimah (the capital Sana'a), Al-Hudaydah, Amran and Hajjah, which are all located in the west of the country. In particular, 77.7% of cholera cases (339,061 of 436,625) and 80.7% of deaths from cholera (1,545 of 1,915) occurred in Houthi -controlled governorates, compared to 15.4% of cases and 10.4% of deaths in government-controlled governorates. Using genomic sequencing, researchers at the Wellcome Sanger Institute and Institut Pasteur concluded the strain of cholera originated in eastern Africa and was carried to Yemen by migrants. Yemen authorities announced the cholera outbreak on October 7, 2016. By the end of that year, there were 96 deaths. Following the October 2016 outbreak, the rate of spread in most areas declined by the end of February 2017, and by mid-March 2017, the outbreak was in decline after a wave of cold weather. A total of 25,827 suspected cases, including 129 deaths, were reported by 26 April 2017. The number of cholera cases resurged in a second wave that began on 27 April 2017. According to Qadri, Islam and Clemens, writing in The New England Journal of Medicine , the dramatic April 2017 resurgence was "coincident with heavy rains that may have contaminated drinking water sources, and was amplified by war-related destruction of municipal water and sewage systems". During May 2017, 74,311 suspected cases, including 605 deaths, were reported. By June, UNICEF and WHO estimated that 5,000 new cases per day were occurring, and that the total number of cases in the country since the outbreak began in October had exceeded 200,000, with 1,300 deaths. The two agencies stated that it was then "the worst cholera outbreak in the world". By 4 July 2017, there were 269,608 cases and the death toll was at 1,614 with a case fatality rate of 0.6%. On 14 August 2017 the WHO updated the number of suspected cholera cases to 500,000. Oxfam said in 2017 the outbreak would become the largest epidemic since record-keeping began, overtaking the 754,373 cases of cholera recorded after the 2010 Haiti earthquake . In six months, more people were ill with cholera in Yemen than in seven years after the earthquake in Haiti, and the situation in Yemen was made worse by hunger and malnutrition. On 22 December 2017, WHO reported the number of suspected cholera cases in Yemen had surpassed one million. By October 2018, there were more than 1.2 million cases reported, and more than 2,500 people—58% children—have died in the Yemen cholera outbreak, which is the worst epidemic in recorded history and was, according to the United Nations (UN), the worst humanitarian crisis in the world. Between 1 January 2018 to 31 May 2020, the cumulative total number of suspected cases was 1,371,819 with 1566 associated deaths. The case fatality rate for the outbreak was 0.11% as of 2020, having declined from a high of 1% when the outbreak first began. UNICEF and the WHO attributed the outbreak to malnutrition , collapsing sanitation and clean water systems due to the country's ongoing conflict, and the approximately 30,000 local health care workers who had not been paid for almost a year. These factors resulted in a delayed vaccination program, which was not started until more than one million people were already ill. Even before civil war affected Yemen, it was "beset by circumstances that made it ripe for cholera". A country with high poverty rates, Yemen also suffered frequent droughts and severe water access problems, with only about half of the population having had access to good water and sanitation before the war. Children under five showed a high prevalence of malnutrition, making them further susceptible to disease; Yemen had "one of the highest rates of childhood malnutrition worldwide". The health care system in Yemen before the conflict was weak and lacking infrastructure. For instance, before the war, 70–80% of children were vaccinated against measles, but the vaccination rate had dropped by the end of 2015. Because of the ongoing conflict in Yemen, and resulting displacement of people who do not have adequate food, waster, housing or sanitation, pre-existing conditions were exacerbated. Shortages have been made worse by naval and air blockades. Bombing has damaged water and sanitation infrastructure. Airstrikes have destroyed facilities in the country for health care; "half of the nation's hospitals have been either destroyed by Saudi airstrikes, occupied by rebel forces, or shut down because there are no medical personnel to staff them". Doctors Without Borders reported that a Saudi Arabian coalition airstrike hit a new Médecins Sans Frontières cholera treatment center in Abs , in northwestern Yemen. Doctors Without Borders reported that they had provided GPS coordinates to Saudi Arabia on twelve separate occasions, and had received nine written responses confirming receipt of those coordinates. Grant Pritchard, Save the Children 's interim country director for Yemen, stated in April 2017, "With the right medicines, these [diseases] are all completely treatable – but the Saudi Arabia-led coalition is stopping them from getting in." Yemen's wastewater and solid waste management systems are the least developed among Middle Eastern countries, which has been a major contributor to the cholera outbreak. With 16 functional sewage treatment plants (STPs) and a growing population, the country's sewage systems are ill-equipped to meet the needs of citizens and serve just 7% of the population. Actual flow rates through the STPs in Yemen exceed the flow rates they were designed to accommodate, which reduces their efficiency. The treatment processes used are also suboptimal, with 68% of STPs using only stabilization ponds - which are generally intended as a primary treatment - to remove pathogens from sewage. This has resulted in high quantities of infectious agents in effluent , which is hazardous to health and can enable the spread of cholera. Moreover, wastewater in Yemen is frequently reused for irrigation purposes by farmers due to a lack of awareness about safety risks. High concentrations of Escherichia coli , Streptococcus faecalis , Klebsiella pneumoniae , Enterobacter aerogenes , Salmonella typhi , S. typhimurium , and Shigella sonnei - among other harmful fecal coliforms - are present in this wastewater, and transmit to humans when they consume foods irrigated by it. Official dumping sites for solid waste are being created increasingly close to communities, which has increased the risk of infection and general health issues among citizens. This is especially true for the roughly 70% of citizens without access to potable water, who consume water from wells near dumping sites. The El Niño–Southern Oscillation phenomenon is a major driver of climate variability associated with health outcomes, including influencing cholera dynamics due to changes in rainfall. For example, in East Africa, there was an upsurge in cholera cases in areas with increased rainfall, along with an increase in cases in areas with decreased rainfall. In the 2015-2016 El Niño event, there were an additional 50 000 cases of cholera in East Africa. Based on genomic approaches, there was a linkage found between the epidemic in Yemen starting in 2016 and the earlier outbreaks in East Africa. This alludes to a possible connection between cholera in East Africa and Yemen. Chironomidae are natural reservoirs and carriers of the Vibrio cholerae bacterium. It has been suggested that adult chironomidae may aerially carry the bacterium between bodies of water, assisting in the transmission of cholera. Based on this evidence, it is hypothesized that the El Nino conditions over the Gulf of Aden may have contributed to the transmission of cholera from the Horn of Africa to Yemen through wind effects on cholera-contaminated flying insects. As of 2016, the government ended funding for public health, leaving many employees without salary. The impacts of the outbreak were exacerbated by the collapse of the Yemeni health services , where many health workers remained unpaid for months. A months-long strike of sanitation workers over unpaid wages contributed to the accumulation of garbage that entered the water supply. Qadri, Islam and Clemens write that the dramatic April 2017 resurgence coincided with heavy rains, and "was amplified by war-related destruction of municipal water and sewage systems". An International Committee of the Red Cross (ICRC) worker in Yemen noted that April's cholera resurgence began ten days after Sana'a's sewer system stopped working. Raslan et al write in Frontiers in Public Health : A failing sewage system, continued conflict and inadequate health care facilities are only a few of the reasons contributing to this problem. Malnutrition, which is a significant consequence of the Yemen War, has further contributed to this outbreak. Epidemiological modelling of the outbreak from October 2016 to January 2016 together with satellite image-derived meteorological data showed that the rainfall had a strong impact in increasing the chances of transmission, with the rainy season of April 2017 having coincided with the onset of the second wave of the outbreak topping at more than 50,000 cases per week. The geography of Yemen means that the Western mountainous plateau sees more rainfall, and has therefore an increased risk of high cholera incidence due to water precipitations. The International Coordinating Group on Vaccine Provision, which maintains vaccine stockpiles for cholera, announced a plan in June 2017 to send one million doses of oral cholera vaccine (OCV) to Yemen, but this plan stalled. Controversy surrounded whether vaccination was the best strategy, whether it was too late to start a vaccination campaign, whether there was enough stockpiled vaccine to meet worldwide needs, whether all of the reported cases of cholera in Yemen were true cases as opposed to simply cases of diarrhea or other similar symptoms, and the effectiveness of the vaccine. The request for vaccine was retracted. In May 2018, the first OCV campaign in Yemen was launched. The WHO and UNICEF delivered oral vaccines to 540,000 individuals in August 2018. Federspiel and Ali write in BMC Public Health : OCVs were not delivered until nearly 3.5 years into this humanitarian emergency, which has most likely been due to ongoing conflict, logistical circumstances, the scale of the epidemic, impairment of the humanitarian response by the parts to the conflict and some degree of negligence from donors, politicians and other decision makers. Whatever the reasons, OCVs were not distributed until nearly 16 months into the cholera outbreak by which time more than a million cases had accumulated. Neither were they in the two years of WaSH infrastructure breakdown that preceded the outbreak. This should serve as a historic example of the failure to control the spread of cholera given the tools that are available. Today, "cholera outbreaks are entirely containable" (The Lancet editorial, 2017). The COVID-19 pandemic in Yemen is part of the worldwide pandemic of coronavirus disease 2019 . As of 12 November 2020, there were 2,070 confirmed cases and 602 deaths. The COVID-19 pandemic has further burdened the already overwhelmed healthcare system in Yemen fighting a number of diseases including cholera, dengue fever, and malaria. Only half of existing health facilities are fully functioning while more than 17.9 million people of a total population of 30 million need health care services in 2020. In addition, those that remain open lack medical personnel, basic medicine, and essential supplies such as masks and gloves. The lack of flights in and out of Yemen to mitigate the pandemic has also restricted the movement of aid workers responding to the humanitarian crisis. Even before civil war affected Yemen, it was "beset by circumstances that made it ripe for cholera". A country with high poverty rates, Yemen also suffered frequent droughts and severe water access problems, with only about half of the population having had access to good water and sanitation before the war. Children under five showed a high prevalence of malnutrition, making them further susceptible to disease; Yemen had "one of the highest rates of childhood malnutrition worldwide". The health care system in Yemen before the conflict was weak and lacking infrastructure. For instance, before the war, 70–80% of children were vaccinated against measles, but the vaccination rate had dropped by the end of 2015. Because of the ongoing conflict in Yemen, and resulting displacement of people who do not have adequate food, waster, housing or sanitation, pre-existing conditions were exacerbated. Shortages have been made worse by naval and air blockades. Bombing has damaged water and sanitation infrastructure. Airstrikes have destroyed facilities in the country for health care; "half of the nation's hospitals have been either destroyed by Saudi airstrikes, occupied by rebel forces, or shut down because there are no medical personnel to staff them". Doctors Without Borders reported that a Saudi Arabian coalition airstrike hit a new Médecins Sans Frontières cholera treatment center in Abs , in northwestern Yemen. Doctors Without Borders reported that they had provided GPS coordinates to Saudi Arabia on twelve separate occasions, and had received nine written responses confirming receipt of those coordinates. Grant Pritchard, Save the Children 's interim country director for Yemen, stated in April 2017, "With the right medicines, these [diseases] are all completely treatable – but the Saudi Arabia-led coalition is stopping them from getting in." Yemen's wastewater and solid waste management systems are the least developed among Middle Eastern countries, which has been a major contributor to the cholera outbreak. With 16 functional sewage treatment plants (STPs) and a growing population, the country's sewage systems are ill-equipped to meet the needs of citizens and serve just 7% of the population. Actual flow rates through the STPs in Yemen exceed the flow rates they were designed to accommodate, which reduces their efficiency. The treatment processes used are also suboptimal, with 68% of STPs using only stabilization ponds - which are generally intended as a primary treatment - to remove pathogens from sewage. This has resulted in high quantities of infectious agents in effluent , which is hazardous to health and can enable the spread of cholera. Moreover, wastewater in Yemen is frequently reused for irrigation purposes by farmers due to a lack of awareness about safety risks. High concentrations of Escherichia coli , Streptococcus faecalis , Klebsiella pneumoniae , Enterobacter aerogenes , Salmonella typhi , S. typhimurium , and Shigella sonnei - among other harmful fecal coliforms - are present in this wastewater, and transmit to humans when they consume foods irrigated by it. Official dumping sites for solid waste are being created increasingly close to communities, which has increased the risk of infection and general health issues among citizens. This is especially true for the roughly 70% of citizens without access to potable water, who consume water from wells near dumping sites. The El Niño–Southern Oscillation phenomenon is a major driver of climate variability associated with health outcomes, including influencing cholera dynamics due to changes in rainfall. For example, in East Africa, there was an upsurge in cholera cases in areas with increased rainfall, along with an increase in cases in areas with decreased rainfall. In the 2015-2016 El Niño event, there were an additional 50 000 cases of cholera in East Africa. Based on genomic approaches, there was a linkage found between the epidemic in Yemen starting in 2016 and the earlier outbreaks in East Africa. This alludes to a possible connection between cholera in East Africa and Yemen. Chironomidae are natural reservoirs and carriers of the Vibrio cholerae bacterium. It has been suggested that adult chironomidae may aerially carry the bacterium between bodies of water, assisting in the transmission of cholera. Based on this evidence, it is hypothesized that the El Nino conditions over the Gulf of Aden may have contributed to the transmission of cholera from the Horn of Africa to Yemen through wind effects on cholera-contaminated flying insects. As of 2016, the government ended funding for public health, leaving many employees without salary. The impacts of the outbreak were exacerbated by the collapse of the Yemeni health services , where many health workers remained unpaid for months. A months-long strike of sanitation workers over unpaid wages contributed to the accumulation of garbage that entered the water supply. Qadri, Islam and Clemens write that the dramatic April 2017 resurgence coincided with heavy rains, and "was amplified by war-related destruction of municipal water and sewage systems". An International Committee of the Red Cross (ICRC) worker in Yemen noted that April's cholera resurgence began ten days after Sana'a's sewer system stopped working. Raslan et al write in Frontiers in Public Health : A failing sewage system, continued conflict and inadequate health care facilities are only a few of the reasons contributing to this problem. Malnutrition, which is a significant consequence of the Yemen War, has further contributed to this outbreak. Epidemiological modelling of the outbreak from October 2016 to January 2016 together with satellite image-derived meteorological data showed that the rainfall had a strong impact in increasing the chances of transmission, with the rainy season of April 2017 having coincided with the onset of the second wave of the outbreak topping at more than 50,000 cases per week. The geography of Yemen means that the Western mountainous plateau sees more rainfall, and has therefore an increased risk of high cholera incidence due to water precipitations. The International Coordinating Group on Vaccine Provision, which maintains vaccine stockpiles for cholera, announced a plan in June 2017 to send one million doses of oral cholera vaccine (OCV) to Yemen, but this plan stalled. Controversy surrounded whether vaccination was the best strategy, whether it was too late to start a vaccination campaign, whether there was enough stockpiled vaccine to meet worldwide needs, whether all of the reported cases of cholera in Yemen were true cases as opposed to simply cases of diarrhea or other similar symptoms, and the effectiveness of the vaccine. The request for vaccine was retracted. In May 2018, the first OCV campaign in Yemen was launched. The WHO and UNICEF delivered oral vaccines to 540,000 individuals in August 2018. Federspiel and Ali write in BMC Public Health : OCVs were not delivered until nearly 3.5 years into this humanitarian emergency, which has most likely been due to ongoing conflict, logistical circumstances, the scale of the epidemic, impairment of the humanitarian response by the parts to the conflict and some degree of negligence from donors, politicians and other decision makers. Whatever the reasons, OCVs were not distributed until nearly 16 months into the cholera outbreak by which time more than a million cases had accumulated. Neither were they in the two years of WaSH infrastructure breakdown that preceded the outbreak. This should serve as a historic example of the failure to control the spread of cholera given the tools that are available. Today, "cholera outbreaks are entirely containable" (The Lancet editorial, 2017). The COVID-19 pandemic in Yemen is part of the worldwide pandemic of coronavirus disease 2019 . As of 12 November 2020, there were 2,070 confirmed cases and 602 deaths. The COVID-19 pandemic has further burdened the already overwhelmed healthcare system in Yemen fighting a number of diseases including cholera, dengue fever, and malaria. Only half of existing health facilities are fully functioning while more than 17.9 million people of a total population of 30 million need health care services in 2020. In addition, those that remain open lack medical personnel, basic medicine, and essential supplies such as masks and gloves. The lack of flights in and out of Yemen to mitigate the pandemic has also restricted the movement of aid workers responding to the humanitarian crisis. Through 2018, several humanitarian healthcare organizations had reported activity to contain the cholera outbreak. The International Committee of the Red Cross have supported 17 treatment centers with supplies including IV fluids , oral rehydration therapy supplies, antibiotics, chlorine tablets, in addition to sending engineers to help restore water distribution in Yemen. The International Rescue Committee (IRC) supplied seven hospitals with medicine and supplies, deployed health teams and trained volunteers, delivered health and nutrition services, and facilitated referrals of malnourished children. The World Health Organization coordinated the Yemen Health Cluster with 40 member organizations, and together with Health and Water Sanitation and Hygiene ( WaSH ) units, explored the use of oral cholera vaccines (OCVs). The WHO reported operating 414 facilities using 406 teams active in 323 districts in Yemen, which included 36 treatment centers for cholera. In the management of cholera, they stated that they trained 900 health workers and ran 139 oral rehydration locations, to treat 700,000 reported cases of the illness. UNICEF reported that they ran awareness campaigns with 20,000 promoters, provided water to more than one million individuals, served as the WaSH lead, and delivered "40 tons of medical equipment including medicine, oral rehydration solution, IV fluids and diarrhea kits". Médecins Sans Frontières (Doctors Without Borders) said it treated at least 103,000 individuals in 37 locations. As of June 2, 2020, Canada has pledged $40 million in humanitarian aid for Yemen to help the politically unstable country cope with cholera, malaria, dengue fever, and diphtheria along with COVID-19. This brings Canada's total contributions to Yemen since 2015 to $220 million, which contributes towards the goal of US$2.4 billion for underfunded humanitarian programs run by UN agencies and humanitarian organizations in Yemen. Saudi Arabia has been backing the Yemen government in the fight against the Houthi rebels, and they are also one of the top donors for UN humanitarian aid operations in Yemen. On 23 June 2017, Saudi Arabia's crown prince, Mohammed bin Salman , authorized a donation in excess of $66 million for cholera relief in Yemen. Mohammed al-Jaber, the Saudi ambassador to Yemen, has announced half a billion dollars from Saudi Arabia to support UN programs in 2020. An aid conference was held in Geneva in April 2017 that raised half of the US$2.1 billion that the United Nations (UN) estimated was needed. As of July 8, 2019, the UN and partners are running 1200 cholera treatment facilities around the country, however, funding is an issue. The 2019 Yemen Humanitarian Response Plan required $4.2 billion to deliver assistance, but they ended up receiving $3.6 billion. For the 2020 plan, the UN has so far received 15% of the necessary $3.5 billion needed. On April 3, 2018, the United States (U.S.) announced $87 million in additional humanitarian assistance to help the people of Yemen, bringing the U.S. total assistance since 2017 to more than $854 million. This money will be used for food assistance, safe drinking water, emergency shelter, and medical supplies. The U.S. is also planning to provide $55 million in economic and development assistance, including programs to support livelihoods, rebuild infrastructure, and restore access to education. On March 27, 2020, the Trump administration cut $70 million in assistance destined for northern Yemen, framing the decreased funding as a response to the interference of Houthi rebels. The U.S. officials were concerned that the assistance was directed to fighters instead of civilians. South Yemen, which is less populous, still received aid dollars. The United Kingdom (UK) government has been one of the largest humanitarian donors to Yemen, budgeting £139 million in 2017/2018 and earmarking £8m from the Yemen budget specifically to respond to cholera. The UK has partnered with organizations including UNICEF and the International Organisation for Migration (IOM) to combat the cholera disease in Yemen. The UK's humanitarian response includes nutrition support, clean water, sanitation, and medical supplies, such as chlorine tablets and hygiene kits. The UK Department for International Development (DFID) has also worked with the Met Office , NASA and U.S. scientists to deploy a model to predict and effectively respond to outbreaks of cholera. DFID Secretary Priti Patel has urged the international community to follow the UK government's steps to curb the cholera outbreak. On August 25, 2017, the World Bank announced $200 million U.S. to support Yemen as it struggles to contain the cholera outbreak. This money is being used to strengthen the country's health, water, and sanitation systems. As of June 2, 2020, Canada has pledged $40 million in humanitarian aid for Yemen to help the politically unstable country cope with cholera, malaria, dengue fever, and diphtheria along with COVID-19. This brings Canada's total contributions to Yemen since 2015 to $220 million, which contributes towards the goal of US$2.4 billion for underfunded humanitarian programs run by UN agencies and humanitarian organizations in Yemen. Saudi Arabia has been backing the Yemen government in the fight against the Houthi rebels, and they are also one of the top donors for UN humanitarian aid operations in Yemen. On 23 June 2017, Saudi Arabia's crown prince, Mohammed bin Salman , authorized a donation in excess of $66 million for cholera relief in Yemen. Mohammed al-Jaber, the Saudi ambassador to Yemen, has announced half a billion dollars from Saudi Arabia to support UN programs in 2020. An aid conference was held in Geneva in April 2017 that raised half of the US$2.1 billion that the United Nations (UN) estimated was needed. As of July 8, 2019, the UN and partners are running 1200 cholera treatment facilities around the country, however, funding is an issue. The 2019 Yemen Humanitarian Response Plan required $4.2 billion to deliver assistance, but they ended up receiving $3.6 billion. For the 2020 plan, the UN has so far received 15% of the necessary $3.5 billion needed. On April 3, 2018, the United States (U.S.) announced $87 million in additional humanitarian assistance to help the people of Yemen, bringing the U.S. total assistance since 2017 to more than $854 million. This money will be used for food assistance, safe drinking water, emergency shelter, and medical supplies. The U.S. is also planning to provide $55 million in economic and development assistance, including programs to support livelihoods, rebuild infrastructure, and restore access to education. On March 27, 2020, the Trump administration cut $70 million in assistance destined for northern Yemen, framing the decreased funding as a response to the interference of Houthi rebels. The U.S. officials were concerned that the assistance was directed to fighters instead of civilians. South Yemen, which is less populous, still received aid dollars. The United Kingdom (UK) government has been one of the largest humanitarian donors to Yemen, budgeting £139 million in 2017/2018 and earmarking £8m from the Yemen budget specifically to respond to cholera. The UK has partnered with organizations including UNICEF and the International Organisation for Migration (IOM) to combat the cholera disease in Yemen. The UK's humanitarian response includes nutrition support, clean water, sanitation, and medical supplies, such as chlorine tablets and hygiene kits. The UK Department for International Development (DFID) has also worked with the Met Office , NASA and U.S. scientists to deploy a model to predict and effectively respond to outbreaks of cholera. DFID Secretary Priti Patel has urged the international community to follow the UK government's steps to curb the cholera outbreak. On August 25, 2017, the World Bank announced $200 million U.S. to support Yemen as it struggles to contain the cholera outbreak. This money is being used to strengthen the country's health, water, and sanitation systems. The WHO provided regular outbreak updates for the epidemic in Yemen up until August 2020. Since then the epidemic has declined in numbers of cases and deaths, with 2020 seeing a total of 230,540 suspected cases and 84 deaths and 5,676 suspected cases with two deaths between January 1 and March 6 of 2021 Furthermore, UNICEF reports that in 2021 over 190,000 children received a cholera vaccine, achieving 94% coverage.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2023—2024_cholera_outbreak_in_South_Africa/html

2023—2024 cholera outbreak in South Africa

On 1 February, 2023, a cholera outbreak began in South Africa. As of 3 March 2024, 1395 cases had been reported. The South African outbreak is thought to originate from two sisters that introduced it into the country after visiting Chinsapo ( Lilongwe ) in Malawi. The initial cases were isolated to Gauteng . As of 21 January 2024, 1499 (or 1395) new suspected cholera cases were reported across all 9 provinces. The first cases of cholera were reported on 1 February 2023. In May, the Gauteng province health department declared an outbreak in Hammanskraal . Fifteen deaths and 41 cases had been recorded as of May 22. Residents blamed the local government for failing to provide adequate potable water. By July 10, nearly 50 deaths had been recorded, most of which occurred in Hammanskraal . On 16 January 2024, the health ministry confirmed two cases through laboratory tests in Limpopo province .

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1817–1824_cholera_pandemic/html

1817–1824 cholera pandemic

The first cholera pandemic (1817–1824), also known as the first Asiatic cholera pandemic or Asiatic cholera , began near the city of Calcutta and spread throughout South Asia and Southeast Asia to the Middle East , Eastern Africa and the Mediterranean coast. While cholera had spread across India many times previously, this outbreak went further; it reached as far as China and the Mediterranean Sea before subsiding. Millions of people died as a result of this pandemic , including many British soldiers , which attracted European attention. This was the first of several cholera pandemics to sweep through Asia and Europe during the 19th and 20th centuries. This first pandemic spread over an unprecedented range of territory, affecting almost every country in Asia.The name cholera had been used in previous centuries to describe illnesses involving nausea and vomiting. Today, cholera specifically describes illness caused by the Vibrio cholerae bacteria. There are numerous examples of epidemics prior to 1817 which are suspected as being cholera. In the sixth century BCE cholera-like symptoms were described by an Indian text. Indeed, descriptions of a disease in India from as far back as 2,500 years ago describe an illness reminiscent of cholera. Greek physician Hippocrates wrote about an illness resembling cholera about 2,400 years ago, as did Roman physician Galen roughly 500 years later in the 2nd century. In the 16th century, an outbreak of acute diarrhea was reported to have occurred in the East Indies by the Dutch. A similar outbreak was recorded in 1669 in China. But, there is not evidence of "true Asiatic Cholera" prior to 1781, in which the first well-documented epidemic occurred. Having begun in southern India, it would later spread to eastern India and eventually Sri Lanka . Cholera was endemic to the lower Ganges River . At festival times, pilgrims frequently contracted the disease there and carried it back to other parts of India on their returns, where it would spread, then subside. The first cholera pandemic started similarly, as an outbreak that was suspected to have begun in 1817 in the town of Jessore . Some epidemiologists and medical historians have suggested that it spread globally through a Hindu pilgrimage, the Kumbh Mela , on the upper Ganges River. Earlier outbreaks of cholera had occurred near Purnia in Bihar , but scholars think these were independent events. In 1817, cholera began spreading outside the Ganges Delta . By September 1817, the disease had reached Calcutta on the Bay of Bengal and quickly spread to the rest of the subcontinent. By 1818 the disease broke out in Bombay , on the west coast.After spreading beyond India, the first cholera pandemic hit other parts of Asia and the African coast the hardest. It would not be until later epidemics of cholera that it would ravage Europe and the Americas. In March 1820, the disease was identified in Siam , in May 1820 it had spread as far as Bangkok and Manila ; in July the outbreak torched Vietnam ; in spring of 1821 it reached Java , Oman , and Anhai in China ; in 1822 it was found in Japan , in the Persian Gulf , in Baghdad , in Syria , and in the Transcaucasus ; and in 1823 cholera reached Astrakhan , Zanzibar , and Mauritius . When the epidemic reached Russia and specifically Astrakhan , their response was to formulate an anti-Cholera program in 1823. This program was headed by a German physician by the name of Dr. Rehmann. The Anti-Cholera program inspired the creation of a medical-administration board by Tsar Alexander I that inspired similar medical administration across Europe. In 1824, transmission of the disease ended. Some researchers believe that may have been due to the cold winter of 1823–1824, which would have killed the bacteria in the water supplies. The spread of the first cholera pandemic was closely linked to warfare and trade. According to economic history professor Donato Gómez-Diaz, "[advances] in commercial exchange and navigation contributed to cholera's dispersion." Navy and merchant ships carried people with the disease to the shores of the Indian Ocean, from Africa to Indonesia, and north to China and Japan. During the Ottoman-Persian War of 1821–1823 , cholera would affect both armies in what is modern-day Armenia. Hindu pilgrims spread cholera within the subcontinent, as had happened many times previously, and British troops carried it overland to Nepal and Afghanistan . In 1821, British troops spread cholera to Oman after becoming infected with it in India. The total deaths from the epidemic remain unknown. Scholars of particular areas have estimated death tolls. For instance, some estimate that Bangkok might have suffered 30,000 deaths from the disease. In Semarang , Central Java, 1,225 people died in eleven days in April 1821. In total, over 100,000 people died as a result of cholera on Java during the first pandemic. Also in 1821, Basra, Iraq saw 18,000 deaths in less than a month's time. In the same year, it is estimated that up to 100,000 deaths occurred in Korea. Vietnamese royal archives recorded 206,835 people died from the disease. In the southwest of the Mekong Delta , the outbreak swept through the constructing Vĩnh Tế Canal , killing thousand of workers (most of them Cambodians) and triggered a Cambodian uprising in later that year. The well-known novelist NguyỠn Du died contracting the disease. As for India, the initially reported mortality rate was estimated to be 1.25 million per year, placing the death toll at around 8,750,000. However, this report was certainly an overestimation as David Arnold writes: "The death toll in 1817–21 was undoubtedly great, but there is no evidence to suggest that it was as uniformly high as Moreau de Jonnès presumed. [...] Statistics collected by James Jameson for the Bengal Medical Board showed mortality in excess of 10,000 in several districts. [...] Although reporting was sketchy, for the Madras districts as a whole the mortality during the height of the epidemic appears to have been around 11 to 12 per 1,000. If this figure were applied to the whole of India, with a population of some 120–150 million, the total number of deaths would have been no more than one or two million." According to historian Samuel Kohn, in antiquity , epidemics frequently brought members of a society together. However, some diseases such as cholera produced the opposite result, triggering blame and even violence against those people who were perceived as being from regions in which people were believed to be infected with the disease. Often times, fear of cholera outbreaks would lead to increased racial tensions. The cholera pandemic's origin in India led to a rise in anti-Asian sentiment, especially towards Indian people and culture , in the West during the initial outbreak and following more outbreaks decades later. The disease was subsequently associated with Asia and South Asia, in particular, was seen as in some way to blame for cholera. Derision towards Indian cultural practices, especially Hindu pilgrimages, and hygiene following the initial outbreak were reported. Speaking about the anti-Asian sentiment that rose after the outbreak, British historian David Arnold wrote that "the Indian origins of cholera and its almost global dissemination from Bengal made the disease a convenient symbol for much that the west feared or despised about a society so different from its own". Medical professionals of the time were also noted for relying on moral judgments and generalizations of Indian people on pilgrimages. The sanitary commissioner of Bengal, David Smith, wrote that "the human mind can scarcely sink lower than it has done in connection with the appalling degeneration of idol-worship at Pooree". During the outbreak, the colonial authorities launched inquiries into the medical conditions of South Asian people on pilgrimages and eventually classified pilgrims as a "dangerous class" due their belief that many pilgrims were infected with cholera, placing them under surveillance. Historian Christopher Hamlin noted that European physicians attempted to distinguish the "new" strain of Asiatic cholera from the "old" strain, and that evidence for a Bengali origin of the pandemic were often based on 19th-century accounts which were "steeped in biases" against Hindu and Indian culture in general. In the years after the pandemic subsided in many areas of the world, there were still small outbreaks, and pockets of cholera remained. In the period from 1823 to 1829, the first cholera outbreak remained outside of much of Europe. Its spread into Europe in the years after the initial outbreak started with the spread of the bacterium to the Russian empire yet again. Historians theorize that the spread back into Europe was largely to due to its movement in the Russian river system and with passengers on the river. This movement of the virus in the rivers of Russia allowed cholera to reach England by 1832, and the Americas shortly afterward. The bacterium also was theorized to have spread into England from British soldiers returning home after tours of duty in India, many of them serving in the Bombay Army which was stationed where the pandemic broke out. Special deputations from the west traveled to Russia to observe the Russian response and formulate a plan to deal with these pocketed outbreaks . Reports from this committee of scientists were bleak, with a Dr. Rauch proclaiming that, "the cholera will not be cured by nature's powers alone without the help of art...". The conclusion of Dr. Rauch's findings was that no one standardized method was the key to controlling an outbreak. By 1835, these pockets of the bacterium claimed hundreds of thousands of lives. This timeline from 1826 to 1837 is widely described as the second cholera pandemic . The last of the seven main cholera pandemics in history extends into the modern day.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2024_Mozambique_boat_disaster/html

2024 Mozambique boat disaster

The makeshift ferry Zico sank on April 7, 2024, between the Mozambique Channel and Mossuril Bay, off the coast of northern Mozambique . Over 100 of the 130 passengers on the overloaded vessel died.Mozambique and other neighboring African countries such as Zimbabwe and Malawi had uncontained cholera outbreaks in the months preceding the disaster. Since October 2023, the country has recorded about 15,000 cases of cholera and 32 deaths due to the disease. Many parts of the country are only accessible by boats, and the country has a poor road network and many parts are inaccessible by air. The disaster occurred despite recent pressure on ferry operators to improve safety. There is little oversight for the thousands of ferries operating in Mozambique and less deadly incidents are not uncommon. The Mozambican vessel Zico , a fishing boat converted for use as a ferry, was traveling from Lunga in Mossuril District, Nampula Province to the Island of Mozambique on 7 April 2024. Most of the 130–150 passengers were trying to escape the mainland because of a cholera outbreak , with Nampula being one of the worst-affected provinces. Others were travelling to attend a fair on the island. Surviving crewmember Menque Amade said that he requested that the crew chief increase the boat's speed once he saw that the boat was adrift. A survivor claimed that the vessel was overcrowded and began to take on water because of the number of people leading to passengers panicking and jumping off the vessel into the sea. The vessel sank off the coast of northern Mozambique between the Mozambique Channel and Mossuril Bay and was later dragged to shore. Over 100 people were killed, including many children. There were 12 survivors, according to provincial officials and as of 9 April 2024 [ update ] , around 20 people were still missing. Bodies washed up on the beach, and some were quickly buried in line with Islamic rites . Authorities initially blamed the sinking on overcrowding but later said the boat sank after taking on water. Early reports also suggested that the boat had been struck by a tidal wave. Nampula province's Secretary of State Jaime Neto said that misinformation about cholera caused people to panic and board the boat. A Maritime Transport Institute official indicated that the boat was not licensed to transport passengers. President Filipe Nyusi ordered an investigation headed by the transport minister, Mateus Magala . A period of national mourning was observed from 10 to 12 April.

Wiki

Cholera

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

Classical swine fever

Classical swine fever ( CSF ) or hog cholera (also sometimes called pig plague based on the German word Schweinepest ) is a highly contagious disease of swine ( Old World and New World pigs ). It has been mentioned as a potential bioweapon . Swine fever causes fever , skin lesions , convulsions , splenic infarctions and usually (particularly in young animals) death within 15 days. [ citation needed ] The disease has acute and chronic forms, and can range from severe, with high mortality, to mild or even unapparent. [ citation needed ] In the acute form of the disease, in all age groups, there is fever, huddling of sick animals, loss of appetite, dullness, weakness, conjunctivitis, constipation followed by diarrhoea, and an unsteady gait. Several days after the onset of clinical signs, the ears, abdomen and inner thighs may show a purple discoloration. Animals with acute disease die within 1–2 weeks. Severe cases of the disease appear very similar to African swine fever . With low-virulence strains, the only expression may be poor reproductive performance and the birth of piglets with neurologic defects such as congenital tremor. A small fraction of the infected pigs may survive and are rendered immune. Artificial immunization procedures were first developed by Marion Dorset . The disease is endemic in much of Asia, [Central and South America, and parts of Europe and Africa. It was believed to have been eradicated in the United Kingdom by 1966 (according to the Department for Environment, Food and Rural Affairs ), but an outbreak occurred in East Anglia in 2000. On January 31, 1978 USDA Secretary Bob Bergland declared that the United States was free of the disease. The appearance of CSF in Italy and Spain was traced by in a retroactive genetic analysis . Greiser-Wilke et al. , 2000 traced these to shipments of piglets from the Netherlands. Other regions believed free of CSF include Australia, Belgium (1998), Canada (1962), Ireland, New Zealand, and Scandinavia. [ citation needed ]The infectious agent responsible is a virus CSFV (previously called hog cholera virus) of the genus Pestivirus in the family Flaviviridae . CSFV is closely related to the ruminant pestiviruses that cause bovine viral diarrhoea and border disease . The effect of different CSFV strains varies widely, leading to a wide range of clinical signs. Highly virulent strains correlate with acute, obvious disease and high mortality, including neurological signs and hemorrhages within the skin. [ citation needed ] Less virulent strains can give rise to subacute or chronic infections that may escape detection, while still causing abortions and stillbirths. In these cases, herds in high-risk areas are usually serologically tested on a thorough statistical basis. [ citation needed ] Infected piglets born to infected but subclinical sows help maintain the disease within a population. Other signs can include lethargy, fever, immunosuppression, chronic diarrhoea, and secondary respiratory infections. The incubation period of CSF ranges from 2 to 14 days, but clinical signs may not be apparent until after 2 to 3 weeks. Preventive state regulations usually assume 21 days as the outside limit of the incubation period. Animals with an acute infection can survive 2 to 3 months before their eventual death. [ citation needed ] Eradicating CSF is problematic. Current programmes revolve around rapid detection, diagnosis, and slaughter. This may possibly be followed by emergency vaccination ( ATCvet codes: QI09AA06 ( WHO ) for the inactivated viral vaccine, QI09AD04 ( WHO ) for the live vaccine). Vaccination is only used where the virus is widespread in the domestic pig population and/or in wild or feral pigs. In the latter case, a slaughter policy alone is usually impracticable. Instead, countries within the EU have implemented hunting restrictions designed to limit the movement of infected boars, as well as using marker and emergency vaccines to inhibit the spread of infection. Possible sources for maintaining and introducing infection include the wide transport of pigs and pork products, as well as endemic CSF within wild boar and feral pig populations.Histology of the brain shows vasculoendothelial proliferation and perivascular cuffing (cuffing is highly suggestive when accompanied by other signs, but is not pathognomonic for the disease).Histology of the brain shows vasculoendothelial proliferation and perivascular cuffing (cuffing is highly suggestive when accompanied by other signs, but is not pathognomonic for the disease).

Wiki

Cholera

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

Oral rehydration therapy

Oral rehydration therapy ( ORT ) is a type of fluid replacement used to prevent and treat dehydration , especially due to diarrhea . It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium . Oral rehydration therapy can also be given by a nasogastric tube . Therapy can include the use of zinc supplements to reduce the duration of diarrhea in infants and children under the age of 5. Use of oral rehydration therapy has been estimated to decrease the risk of death from diarrhea by up to 93%. Side effects may include vomiting , high blood sodium , or high blood potassium . If vomiting occurs, it is recommended that use be paused for 10 minutes and then gradually restarted. The recommended formulation includes sodium chloride , sodium citrate , potassium chloride , and glucose . Glucose may be replaced by sucrose and sodium citrate may be replaced by sodium bicarbonate , if not available, although the resulting mixture is not shelf stable in high-humidity environments. It works as glucose increases the uptake of sodium and thus water by the intestines , and the potassium chloride and sodium citrate help prevent hypokalemia and acidosis , respectively, which are both common side effects of diarrhea. A number of other formulations are also available including versions that can be made at home. However, the use of homemade solutions has not been well studied. Oral rehydration therapy was developed in the 1940s using electrolyte solutions with or without glucose on an empirical basis chiefly for mild or convalescent patients, but did not come into common use for rehydration and maintenance therapy until after the discovery that glucose promoted sodium and water absorption during cholera in the 1960s. It is on the World Health Organization's List of Essential Medicines . Globally, as of 2015 [ update ] , oral rehydration therapy is used by 41% of children with diarrhea. This use has played an important role in reducing the number of deaths in children under the age of five . ORT is less invasive than the other strategies for fluid replacement, specifically intravenous (IV) fluid replacement. Mild to moderate dehydration in children seen in an emergency department is best treated with ORT. Persons taking ORT should eat within six hours and return to their full diet within 24–48 hours. Oral rehydration therapy may also be used as a treatment for the symptoms of dehydration and rehydration in burns in resource-limited settings. ORT may lower the mortality rate of diarrhea by as much as 93%. Case studies in four developing countries also have demonstrated an association between increased use of ORS and reduction in mortality. ORT using the original ORS formula has no effect on the duration of the diarrheic episode or the volume of fluid loss, although reduced osmolarity solutions have been shown to reduce stool volume. The degree of dehydration should be assessed before initiating ORT. ORT is suitable for people who are not dehydrated and those who show signs and symptoms of mild to moderate dehydration. People who have severe dehydration should seek professional medical help immediately and receive intravenous rehydration as soon as possible to rapidly replenish fluid volume in the body. ORT may lower the mortality rate of diarrhea by as much as 93%. Case studies in four developing countries also have demonstrated an association between increased use of ORS and reduction in mortality. ORT using the original ORS formula has no effect on the duration of the diarrheic episode or the volume of fluid loss, although reduced osmolarity solutions have been shown to reduce stool volume. The degree of dehydration should be assessed before initiating ORT. ORT is suitable for people who are not dehydrated and those who show signs and symptoms of mild to moderate dehydration. People who have severe dehydration should seek professional medical help immediately and receive intravenous rehydration as soon as possible to rapidly replenish fluid volume in the body. ORT should be discontinued and fluids replaced intravenously when vomiting is protracted despite proper administration of ORT; or signs of dehydration worsen despite giving ORT; or the person is unable to drink due to a decreased level of consciousness; or there is evidence of intestinal blockage or ileus . ORT might also be contraindicated in people who are in hemodynamic shock due to impaired airway protective reflexes. Short-term vomiting is not a contraindication to receiving oral rehydration therapy. In persons who are vomiting, drinking oral rehydration solution at a slow and continuous pace will help resolve vomiting. WHO and UNICEF have jointly developed official guidelines for the manufacture of oral rehydration solution and the oral rehydration salts used to make it (both often abbreviated ORS ). They also describe other acceptable solutions, depending on material availability. Commercial preparations are available as prepared fluids and as packets of powder ready to mix with water. A basic oral rehydration therapy solution can also be prepared when packets of oral rehydration salts are not available. The molar ratio of sugar to salt should be 1:1 and the solution should not be hyperosmolar . The Rehydration Project states, "Making the mixture a little diluted (with more than 1 litre of clean water) is not harmful." The optimal fluid for preparing oral rehydration solution is clean water. However, if this is not available, the usually available water should be used. Oral rehydration solution should not be withheld simply because the available water is potentially unsafe; rehydration takes precedence. When oral rehydration salts packets and suitable teaspoons for measuring sugar and salt are not available, the WHO has recommended that homemade gruels, soups, etc., may be considered to help maintain hydration. A Lancet review in 2013 emphasized the need for more research on appropriate home made fluids to prevent dehydration. Sports drinks are not optimal oral rehydration solutions, but they can be used if optimal choices are not available. They should not be withheld for lack of better options; again, rehydration takes precedence. But they are not replacements for oral rehydration solutions in nonemergency situations. In 2003, WHO and UNICEF recommended that the osmolarity of oral rehydration solution be reduced from 311 to 245 mOsm/L. These guidelines were also updated in 2006. This recommendation was based on multiple clinical trials showing that the reduced osmolarity solution reduces stool volume in children with diarrhea by about twenty-five percent and the need for IV therapy by about thirty percent when compared to standard oral rehydration solution. The incidence of vomiting is also reduced. The reduced osmolarity oral rehydration solution has lower concentrations of glucose and sodium chloride than the original solution, but the concentrations of potassium and citrate are unchanged. The reduced osmolarity solution has been criticized by some for not providing enough sodium for adults with cholera. Clinical trials have, however, shown reduced osmolarity solution to be effective for adults and children with cholera. They seem to be safe but some caution is warranted according to the Cochrane review . In 2003, WHO and UNICEF recommended that the osmolarity of oral rehydration solution be reduced from 311 to 245 mOsm/L. These guidelines were also updated in 2006. This recommendation was based on multiple clinical trials showing that the reduced osmolarity solution reduces stool volume in children with diarrhea by about twenty-five percent and the need for IV therapy by about thirty percent when compared to standard oral rehydration solution. The incidence of vomiting is also reduced. The reduced osmolarity oral rehydration solution has lower concentrations of glucose and sodium chloride than the original solution, but the concentrations of potassium and citrate are unchanged. The reduced osmolarity solution has been criticized by some for not providing enough sodium for adults with cholera. Clinical trials have, however, shown reduced osmolarity solution to be effective for adults and children with cholera. They seem to be safe but some caution is warranted according to the Cochrane review . ORT is based on evidence that water continues to be absorbed from the gastrointestinal tract even while fluid is lost through diarrhea or vomiting. The World Health Organization specify indications, preparations and procedures for ORT. WHO/UNICEF guidelines suggest ORT should begin at the first sign of diarrhea in order to prevent dehydration. Babies may be given ORS with a dropper or a syringe. Infants under two may be given a teaspoon of ORS fluid every one to two minutes. Older children and adults should take frequent sips from a cup, with a recommended intake of 200–400 mL of solution after every loose movement. The WHO recommends giving children under two a quarter- to a half-cup of fluid following each loose bowel movement and older children a half- to a full cup. If the person vomits, the caregiver should wait 5–10 minutes and then resume giving ORS. : Section 4.2 ORS may be given by aid workers or health care workers in refugee camps, health clinics and hospital settings. Mothers should remain with their children and be taught how to give ORS. This will help to prepare them to give ORT at home in the future. Breastfeeding should be continued throughout ORT. As part of oral rehydration therapy, the WHO recommends supplemental zinc (10 to 20 mg daily) for ten to fourteen days, to reduce the severity and duration of the illness and make recurrent illness in the following two to three months less likely. Preparations are available as a zinc sulfate solution for adults, a modified solution for children and in tablet form. After severe dehydration is corrected and appetite returns, feeding the person speeds the recovery of normal intestinal function, minimizes weight loss and supports continued growth in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to breastfeed . A child with watery diarrhea typically regains their appetite as soon as dehydration is corrected, whereas a child with bloody diarrhea often eats poorly until the illness resolves. Such children should be encouraged to resume normal feeding as soon as possible. Once diarrhea is corrected, the WHO recommends giving the child an extra meal each day for two weeks, and longer if the child is malnourished. Dehydration may be overestimated in wasted children and underestimated in edematous children. Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration include an eagerness to drink, lethargy, cool and moist extremities, weak or absent radial pulse (wrist), and reduced or absent urine flow. In children with severe malnutrition, it is often impossible to reliably distinguish between moderate and severe dehydration. A severely malnourished child who has signs of severe dehydration but who does not have a history of watery diarrhea should be treated for septic shock . The original ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both contain too much sodium and too little potassium for severely malnourished children with dehydration due to diarrhea. ReSoMal ( Re hydration So lution for Mal nutrition) is recommended for such children. It contains less sodium (45 mmol/L) and more potassium (40 mmol/L) than reduced osmolarity ORS. It can be obtained in packets produced by UNICEF or other manufacturers. [ citation needed ] An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), in which case standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended. Malnourished children should be rehydrated slowly. The WHO recommends 10 milliliters of ReSoMal per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 mL of ReSoMal over the course of the first hour, and another 90 mL for the second hour) and then continuing at this same rate or slower based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethargic. If the child drinks poorly, a nasogastric tube should be used. The IV route should not be used for rehydration except in cases of shock and then only with care, infusing slowly to avoid flooding the circulation and overloading the heart. Feeding should usually resume within 2–3 hours after starting rehydration and should continue every 2–3 hours, day and night. For an initial cereal diet before a child regains his or her full appetite, the WHO recommends combining 25 grams skimmed milk powder, 20 grams vegetable oil, 60 grams sugar, and 60 grams rice powder or other cereal into 1,000 milliliters water and boiling gently for five minutes. Give 130 mL per kilogram of body weight during per 24 hours. A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six equal feedings. Later on, the child should be given cereal made with a greater amount of skimmed milk product and vegetable oil and slightly less sugar. As appetite fully returns, the child should be eating 200 mL per kilogram of body weight per day. Zinc, potassium, vitamin A, and other vitamins and minerals should be added to both recommended cereal products, or to the oral rehydration solution itself. Children who are breastfed should continue breastfeeding. The WHO recommends that all severely malnourished children admitted to hospital should receive broad-spectrum antibiotics (for example, gentamicin and ampicillin ). In addition, hospitalized children should be checked daily for other specific infections. If cholera is suspected give an antibiotic to which V. cholera e are susceptible. This reduces the volume loss due to diarrhea by 50% and shortens the duration of diarrhea to about 48 hours. As part of oral rehydration therapy, the WHO recommends supplemental zinc (10 to 20 mg daily) for ten to fourteen days, to reduce the severity and duration of the illness and make recurrent illness in the following two to three months less likely. Preparations are available as a zinc sulfate solution for adults, a modified solution for children and in tablet form. After severe dehydration is corrected and appetite returns, feeding the person speeds the recovery of normal intestinal function, minimizes weight loss and supports continued growth in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to breastfeed . A child with watery diarrhea typically regains their appetite as soon as dehydration is corrected, whereas a child with bloody diarrhea often eats poorly until the illness resolves. Such children should be encouraged to resume normal feeding as soon as possible. Once diarrhea is corrected, the WHO recommends giving the child an extra meal each day for two weeks, and longer if the child is malnourished. Dehydration may be overestimated in wasted children and underestimated in edematous children. Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration include an eagerness to drink, lethargy, cool and moist extremities, weak or absent radial pulse (wrist), and reduced or absent urine flow. In children with severe malnutrition, it is often impossible to reliably distinguish between moderate and severe dehydration. A severely malnourished child who has signs of severe dehydration but who does not have a history of watery diarrhea should be treated for septic shock . The original ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both contain too much sodium and too little potassium for severely malnourished children with dehydration due to diarrhea. ReSoMal ( Re hydration So lution for Mal nutrition) is recommended for such children. It contains less sodium (45 mmol/L) and more potassium (40 mmol/L) than reduced osmolarity ORS. It can be obtained in packets produced by UNICEF or other manufacturers. [ citation needed ] An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), in which case standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended. Malnourished children should be rehydrated slowly. The WHO recommends 10 milliliters of ReSoMal per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 mL of ReSoMal over the course of the first hour, and another 90 mL for the second hour) and then continuing at this same rate or slower based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethargic. If the child drinks poorly, a nasogastric tube should be used. The IV route should not be used for rehydration except in cases of shock and then only with care, infusing slowly to avoid flooding the circulation and overloading the heart. Feeding should usually resume within 2–3 hours after starting rehydration and should continue every 2–3 hours, day and night. For an initial cereal diet before a child regains his or her full appetite, the WHO recommends combining 25 grams skimmed milk powder, 20 grams vegetable oil, 60 grams sugar, and 60 grams rice powder or other cereal into 1,000 milliliters water and boiling gently for five minutes. Give 130 mL per kilogram of body weight during per 24 hours. A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six equal feedings. Later on, the child should be given cereal made with a greater amount of skimmed milk product and vegetable oil and slightly less sugar. As appetite fully returns, the child should be eating 200 mL per kilogram of body weight per day. Zinc, potassium, vitamin A, and other vitamins and minerals should be added to both recommended cereal products, or to the oral rehydration solution itself. Children who are breastfed should continue breastfeeding. The WHO recommends that all severely malnourished children admitted to hospital should receive broad-spectrum antibiotics (for example, gentamicin and ampicillin ). In addition, hospitalized children should be checked daily for other specific infections. If cholera is suspected give an antibiotic to which V. cholera e are susceptible. This reduces the volume loss due to diarrhea by 50% and shortens the duration of diarrhea to about 48 hours. Fluid from the body enters the intestinal lumen during digestion . This fluid is isosmotic with the blood and contains a high quantity, about 142 mEq/L, of sodium . A healthy individual secretes 2000–3000 milligrams of sodium per day into the intestinal lumen. Nearly all of this is reabsorbed so that sodium levels in the body remain constant . In a diarrheal illness, sodium-rich intestinal secretions are lost before they can be reabsorbed. This can lead to life-threatening dehydration or electrolyte imbalances within hours when fluid loss is severe. The objective of therapy is the replenishment of sodium and water losses by ORT or intravenous infusion. Sodium absorption occurs in two stages. The first is via intestinal epithelial cells ( enterocytes ). Sodium passes into these cells by co-transport with glucose, via the SGLT1 protein. From the intestinal epithelial cells, sodium is pumped by active transport via the sodium-potassium pump through the basolateral cell membrane into the extracellular space . The sodium–potassium ATPase pump at the basolateral cell membrane moves three sodium ions into the extracellular space, while pulling into the enterocyte two potassium ions. This creates a "downhill" sodium gradient within the cell. SGLT proteins use energy from this downhill sodium gradient to transport glucose across the apical membrane of the cell against the glucose gradient. The co-transporters are examples of secondary active transport . The GLUT uniporters then transport glucose across the basolateral membrane. Both SGLT1 and SGLT2 are known as symporters , since both sodium and glucose are transported in the same direction across the membrane. [ citation needed ] The co-transport of glucose into epithelial cells via the SGLT1 protein requires sodium. Two sodium ions and one molecule of glucose (or galactose ) are transported together across the cell membrane via the SGLT1 protein. Without glucose, intestinal sodium is not absorbed. This is why oral rehydration salts include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell to maintain osmotic equilibrium. The resultant absorption of sodium and water can achieve rehydration even while diarrhea continues. In the early 1980s, "oral rehydration therapy" meant only the preparation prescribed by the World Health Organization (WHO) and UNICEF . In 1988, the definition was changed to include recommended home-made solutions, because the official preparation was not always available. The definition was also amended in 1988, to include continued feeding as associated therapy. In 1991, the definition became "an increase in administered hydrational fluids "; in 1993, "an increase in administered fluids and continued feeding". Dehydration was a major cause of death during the 1829 cholera pandemic in Russia and Western Europe. In 1831, William Brooke O'Shaughnessy noted the changes in blood composition and loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (IV fluids), first administered by Latta. The prescribing of hypertonic IV therapy by Rogers [ who? ] decreased the mortality rate of cholera to 40 percent, from 70. In the West, IV therapy became the "gold standard" for the treatment of moderate and severe dehydration. In 1953, Hemendra Nath Chatterjee published in The Lancet the results of using ORT to treat people with mild cholera. He gave the solution orally and rectally, along with Coleus extract, antihistimines, and antiemetics, without controls. The formula of the fluid replacement solution was 4 g of sodium chloride , 25 g of glucose , and 1000 mL of water . He did not publish any balance data, and his exclusion of patients with severe dehydration did not lead to any confirming study; his report remained anecdotal. [ citation needed ] Robert Allan Phillips tried to make an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride could be absorbed in patients with cholera; but he failed because his solution was too hypertonic and he used it to try to stop the diarrhea rather than to rehydrate patients. [ citation needed ] In the early 1960s, Robert K. Crane described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. This, along with evidence that the intestinal mucosa appears undamaged in cholera, suggested that intestinal absorption of glucose and sodium might continue during the illness. This supported the notion that oral rehydration might be possible even during severe diarrhea due to cholera. In 1967–1968, Norbert Hirschhorn and Nathaniel F. Pierce showed that people with severe cholera can absorb glucose, salt, and water and that this can occur in sufficient amounts to maintain hydration. In 1968, David R. Nalin and Richard A. Cash , helped by Rafiqul Islam and Majid Molla, reported that giving adults with cholera an oral glucose-electrolyte solution in volumes equal to those of the diarrhea losses reduced the need for IV fluid therapy by eighty percent. In 1971, fighting during the Bangladesh Liberation War displaced millions and an epidemic of cholera ensued among the refugees. When IV fluid ran out in the refugee camps , Dilip Mahalanabis , a physician working with the Johns Hopkins International Center for Medical Research and Training in Calcutta, issued instructions to prepare an oral rehydration solution and to distribute it to family members and caregivers. Over 3,000 people with cholera received ORT in this way. The mortality rate was 3.6 percent among those given ORT, compared with 30 percent in those given IV fluid therapy. After Bangladesh won independence, there was a wide campaign to promote the use of saline in the treatment of diarrhea. In 1980, the World Health Organization recognized ORT and began a global program for its dissemination. [ citation needed ] In the 1970s, Norbert Hirschhorn used oral rehydration therapy on the White River Apache Indian Reservation with a grant from the National Institute of Allergy and Infectious Diseases. He observed that children voluntarily drank as much of the solution as needed to restore hydration, and that rehydration and early re-feeding would protect their nutrition. This led to increased use of ORT for children with diarrhea, especially in developing countries. [ citation needed ] In 1980, the Bangladeshi nonprofit BRAC created a door-to-door and person-to-person sales force to teach ORT for use by mothers at home. A task force of fourteen women, one cook and one male supervisor traveled from village to village. After visiting with women in several villages, they hit upon the idea of encouraging the women in the village to make their own oral rehydration fluid. They used available household equipment, starting with a "half a seer" (half a quart) of water and adding a fistful of sugar and a three-finger pinch of salt. Later on, the approach was broadcast over television and radio and a market for oral rehydration salts packets developed. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluids at home or in a health facility. ORT is known in Bangladesh as Orosaline or Orsaline. [ citation needed ] From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received an oral rehydration solution, with estimates ranging from 30% to 41% depending on the region. ORT is one of the principal elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunization; female education; family spacing and food supplementation ). The program aims to increase child survival in developing nations through proven low-cost interventions. People had fled from civil war in Mozambique to southern Malawi . In November 1990, cholera broke out in a refugee camp in southern Malawi where approximately 74,000 persons were temporarily living. David Swerdlow of the U.S.'s CDC Epidemic Intelligence Service (EIS) wrote about the situation. He recommended setting up a tent just for children who would be assisted by some of the best nurses. He recommended against over-reliance on IV tubes, which often were left attached to persons for a week or more and which could lead to infections and septic shock. And he noticed that sick persons were not drinking enough rehydration solution. He assigned so-called "ORS officers" whose job was to encourage persons to drink more solution. It was a minor mystery how persons were getting sick since deep-bore wells provided clean water and refugees were encouraged to wash their hands. It was then discovered that the only place for persons to wash hands were in the same buckets in which water was transported and stored. Swerdlow wrote in his report, "Use of narrow mouthed water containers would probably decrease the likelihood of contamination." In the early 1980s, "oral rehydration therapy" meant only the preparation prescribed by the World Health Organization (WHO) and UNICEF . In 1988, the definition was changed to include recommended home-made solutions, because the official preparation was not always available. The definition was also amended in 1988, to include continued feeding as associated therapy. In 1991, the definition became "an increase in administered hydrational fluids "; in 1993, "an increase in administered fluids and continued feeding". Dehydration was a major cause of death during the 1829 cholera pandemic in Russia and Western Europe. In 1831, William Brooke O'Shaughnessy noted the changes in blood composition and loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (IV fluids), first administered by Latta. The prescribing of hypertonic IV therapy by Rogers [ who? ] decreased the mortality rate of cholera to 40 percent, from 70. In the West, IV therapy became the "gold standard" for the treatment of moderate and severe dehydration. In 1953, Hemendra Nath Chatterjee published in The Lancet the results of using ORT to treat people with mild cholera. He gave the solution orally and rectally, along with Coleus extract, antihistimines, and antiemetics, without controls. The formula of the fluid replacement solution was 4 g of sodium chloride , 25 g of glucose , and 1000 mL of water . He did not publish any balance data, and his exclusion of patients with severe dehydration did not lead to any confirming study; his report remained anecdotal. [ citation needed ] Robert Allan Phillips tried to make an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride could be absorbed in patients with cholera; but he failed because his solution was too hypertonic and he used it to try to stop the diarrhea rather than to rehydrate patients. [ citation needed ] In the early 1960s, Robert K. Crane described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. This, along with evidence that the intestinal mucosa appears undamaged in cholera, suggested that intestinal absorption of glucose and sodium might continue during the illness. This supported the notion that oral rehydration might be possible even during severe diarrhea due to cholera. In 1967–1968, Norbert Hirschhorn and Nathaniel F. Pierce showed that people with severe cholera can absorb glucose, salt, and water and that this can occur in sufficient amounts to maintain hydration. In 1968, David R. Nalin and Richard A. Cash , helped by Rafiqul Islam and Majid Molla, reported that giving adults with cholera an oral glucose-electrolyte solution in volumes equal to those of the diarrhea losses reduced the need for IV fluid therapy by eighty percent. In 1971, fighting during the Bangladesh Liberation War displaced millions and an epidemic of cholera ensued among the refugees. When IV fluid ran out in the refugee camps , Dilip Mahalanabis , a physician working with the Johns Hopkins International Center for Medical Research and Training in Calcutta, issued instructions to prepare an oral rehydration solution and to distribute it to family members and caregivers. Over 3,000 people with cholera received ORT in this way. The mortality rate was 3.6 percent among those given ORT, compared with 30 percent in those given IV fluid therapy. After Bangladesh won independence, there was a wide campaign to promote the use of saline in the treatment of diarrhea. In 1980, the World Health Organization recognized ORT and began a global program for its dissemination. [ citation needed ] In the 1970s, Norbert Hirschhorn used oral rehydration therapy on the White River Apache Indian Reservation with a grant from the National Institute of Allergy and Infectious Diseases. He observed that children voluntarily drank as much of the solution as needed to restore hydration, and that rehydration and early re-feeding would protect their nutrition. This led to increased use of ORT for children with diarrhea, especially in developing countries. [ citation needed ] In 1980, the Bangladeshi nonprofit BRAC created a door-to-door and person-to-person sales force to teach ORT for use by mothers at home. A task force of fourteen women, one cook and one male supervisor traveled from village to village. After visiting with women in several villages, they hit upon the idea of encouraging the women in the village to make their own oral rehydration fluid. They used available household equipment, starting with a "half a seer" (half a quart) of water and adding a fistful of sugar and a three-finger pinch of salt. Later on, the approach was broadcast over television and radio and a market for oral rehydration salts packets developed. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluids at home or in a health facility. ORT is known in Bangladesh as Orosaline or Orsaline. [ citation needed ] From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received an oral rehydration solution, with estimates ranging from 30% to 41% depending on the region. ORT is one of the principal elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunization; female education; family spacing and food supplementation ). The program aims to increase child survival in developing nations through proven low-cost interventions. People had fled from civil war in Mozambique to southern Malawi . In November 1990, cholera broke out in a refugee camp in southern Malawi where approximately 74,000 persons were temporarily living. David Swerdlow of the U.S.'s CDC Epidemic Intelligence Service (EIS) wrote about the situation. He recommended setting up a tent just for children who would be assisted by some of the best nurses. He recommended against over-reliance on IV tubes, which often were left attached to persons for a week or more and which could lead to infections and septic shock. And he noticed that sick persons were not drinking enough rehydration solution. He assigned so-called "ORS officers" whose job was to encourage persons to drink more solution. It was a minor mystery how persons were getting sick since deep-bore wells provided clean water and refugees were encouraged to wash their hands. It was then discovered that the only place for persons to wash hands were in the same buckets in which water was transported and stored. Swerdlow wrote in his report, "Use of narrow mouthed water containers would probably decrease the likelihood of contamination."

Wiki

Cholera

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

Cholera epidemics in Spain

The cholera epidemics in Spain were a series of morbid cholera outbreaks that occurred from the first third of the 19th century until the end of the same century in the large cities of Spain . In total, some 800,000 people died during the four pandemics that occurred in Spain during that century. However, cholera was one of several contagious diseases that struck the country. Suffice it to say that the Spanish population in 1800 was 11.5 million people and was characterized by a high birth and death rate . The successive pandemics that the country suffered caused an economic recession , as well as an opportunity for profound change in health and hygiene in Spain. It was not free of controversy, both for the use of the vaccines created by Jaime Ferrán y Clúa and for the ways of combating the disease, as well as for the policies used to deal with it. It is worth mentioning that the terror caused in the population, due to the deaths caused, was the cause of popular revolts and social instability. Since the first outbreak in 1817 , which occurred in India , it has been known as a pandemic disease. Its subsequent spread throughout successive European countries finally led to the appearance of the first cases in Spain. The first outbreak occurred in early 1833, in the port of Vigo , which was repeated almost simultaneously in southern Spain (Andalusia). The first outbreak arose in a conflictive and unstable political environment, in the midst of a severe political transition. The then very recent death of Ferdinand VII after the Ominous Decade left a weak and conflict-ridden state, the first outbreaks occurred during what would become the First Carlist War that was taking place in northern Spain. In 1884, Robert Koch discovered the origin of the disease in the form of a bacillus ; the fight against its advance already had a scientific sense from that year on, however epidemic outbreaks appeared throughout the world. In the 20th century, there were only two outbreaks of cholera in Spain, in 1971 and 1979. Cholera is an infectious disease caused by enterotoxins of the bacillus Vibrio cholerae . The patients show a syndrome based on vomiting and excessive diarrhea (called cholerine ) with watery stools with little or no fever, after an incubation period of one or two days. Death occurs from dehydration in less than a week. The disease is usually transmitted by water and food. When the outbreak becomes established in a population, it is the abundant stools (more than thirty times a day) that easily contaminate drinking water sources and the clothes of the affected persons. It spreads easily in humid areas, and its incidence is higher in countries with a warm climate. The disease arrived in Europe between 1817 and 1823 from India . It struck various parts of Europe from this date onwards, and its victims numbered several million. Finally, on February 2, 1884, Dr. Robert Koch discovered the bacillus causing the disease in the feces of patients. Before this date, all cures were scientifically meaningless lucubrations, since many of the doctors were attached to the miasmatic theory . Many of the prophylactic activities were based on bloodletting , which due to its abundance produced deaths by exsanguination. Emollient and mucilaginous enemas were frequent. After Koch's discovery, Dr. Jaime Ferrán y Clúa tested a vaccine in Spain a year later, which was widely criticized by scientists and politicians. To this criticism contributed the Spaniard Santiago Ramón y Cajal , who denied the effectiveness of the method proposed by Jaime. Finally, the vaccine is not officially approved, and only until June 1919, at an international congress on hygiene held in Paris, it was finally accepted publicly. At present, penicillins are not used for its cure: with a solution of tetracycline its effects are considerably reduced. The current treatment consists of rehydration of the patient with mineral salts , either intravenously or orally. Cholera disease seems to have disappeared in Europe and America at the end of the 19th century, and since 1950 only sporadic outbreaks have occurred in India and nearby countries such as Bangladesh . However, the World Health Organization (WHO) records new outbreaks every year in different parts of the world, generally in developing countries . Nevertheless, two new outbreaks appeared in Spain in the mid-twentieth century, which were relatively easily contained, and in which the number of victims was low, compared to the outbreaks of the 19th century.One of the characteristics of the initial evolution of cholera is that each infected country tried to solve the problem on its own, without requesting help from the rest and without taking any joint action or providing any information to other nations. In Spain, it happened in the same way. Infectious diseases are a common form of mortality, and at the beginning of the 20th century, deaths from infectious diseases still accounted for almost a quarter of all deaths. Cholera was one of the most feared by society, but it was not the only one that plagued the country: yellow fever and smallpox were examples. The mortality from the different outbreaks caused about 300 000 deaths in the period 1833-1834, about 236 000 deaths in 1854-1855, about 120 000 in 1865 and another 120 000 in 1885. It can be seen that the last outbreak occurred when the cause of the disease was already known. Cholera affected in its various outbreaks mainly the eastern half of the Iberian Peninsula , and particularly the densely populated urban centers on the coast and some of them also in the interior. Since the disease appeared in Great Britain in 1832, there was concern in Spain about its origin, prevention and treatment. However, since the etiology of the disease was unknown, preventive actions were trials without any scientific basis. The administration took preventive measures to stop the advance of the disease, believing in the classic epidemic theories of the time. Dr. Pedro Castelló obtained from Fernando VII the authorization to send, in February 1832, a medical commission composed of Pedro María Rubio , Lorenzo Sánchez Núñez and Francisco Paula y Folch , in order to study the effects of cholera in cities such as Paris, Vienna and Munich. The result of their trip was the report sent from Berlin on May 31, 1833, which was not published until 1834. The appearance of the first outbreak in the peninsula from 1832 onwards was a question of time. Some of the measures were based on the creation of sanitary cordons , quarantines in the lazarettos , sectorized isolation of the population, and the establishment of hospitals. The hygienic conditions of some populated cities were improved, cleaning the streets more frequently. A Plan for the Cure of Morbid Cholera was published. The first controversy arose when the cords began to be applied to certain segments of the population: some doctors did not agree with the application of cords because of their dubious efficiency, besides the fact that they paralyzed economic activities. Some physicians, however, agreed with the measures and adopted them at their own discretion in the absence of a central health authority. At this time in the 19th century, cholera was considered an epidemic disease, not at all contagious, and therefore it was thought that the best course of action was to have good hygiene in order not to get it. The Plan for the Cure of Morbid Cholera gave numerous indications in this respect. It was mentioned that the main cause of cholera resided in the atmosphere itself. Prophylactic actions were carried out, such as taking the sale of fruits and vegetables out of the cities. Local Health Boards were established. The main pathogenic theories on morbidity were nervous, spasmodic, humoral and gastroenteric or inflammatory. One of the doctors who stood out in the first outbreaks was the hygienist Mateo Seoane Sobral , who published several articles on the evolution of pandemics in Europe, compiling the experiences of other countries in the treatment of the disease. In the same way, the precursor of Spanish epidemiology, Nicasio Landa y Álvarez de Carvallo carried out numerous statistical studies (medical topography, incidence rates, lethality rates, etc.) that allow studying the evolution of the disease today, especially those corresponding to the second outbreak of 1855. Nine months had passed since cholera had arrived in Paris , and a year and a half since it had arrived in England, and the Spanish and Portuguese authorities knew that it was only a matter of time before the first outbreak appeared on the peninsula. The first cases of the disease occurred in the city of Vigo , in January 1833. The first affected person was named Francisco Conde, and lived in the vicinity of the Vigo arsenal. In Barcelona, an outbreak occurred almost simultaneously. The outbreak started due to the landing of combat troops from the Portuguese War of Succession ; it is possible that they were responsible for their arrival in Spain, and it was in Andalusia where the most deadly cases occurred in the summer of that same year. The arrival of winter slowed the advance of the pandemic throughout the country, and when spring arrived, the disease reached Madrid in a second advance. From Vigo it spread to Pontevedra , and was isolated in that area of Galicia . Other stories mention that the disease came aboard the steamship Isabel la Católica , which came from Greece; in it, three sick people were traveling and were isolated in the corresponding lazaretto. However, days later cases appeared in Redondela , Tuy , Vigo, Pontevedra and in almost all the towns of the province. The outbreak in southern Spain was more virulent, and spread with great force due to environmental conditions, reaching Madrid , Toledo , Guadalajara , Soria , Avila , Burgos and Cuenca . In the capital, already in July 1834, the terror of the disease was of such intensity that there were massacres of friars , accused of causing the disease by poisoning the water. The event was reported in the local press. Everyone began to be suspected, the water carriers , the pharmacists, the doctors. The number of complaints of people suspected of contaminating the water multiplied. There was a third route of entry of the cholera of 1834 through the Mediterranean , the Balearic Islands and Tarragona . One of the causes was the French ship Triton , which had left Toulon with soldiers of the foreign legion on a long voyage that included Oran and Algiers . Cases of cholera on the ship began as soon as it left Toulon and, despite quarantining and sanitizing with lime, the ship spread cholera to the cities where it stopped, such as Tarragona and Roses . This first epidemic affected some 1,394 towns, the last province affected was Cáceres and the last town was Ceclavín . The epidemic lasted a total of one year, five months and twenty-two days. From the first outbreak almost 300,000 people were affected, three percent of the population. On November 19, 1853, the disease returned to the port of Vigo, through the steamship Isabel La Católica . The ship and its crew remained in quarantine in the lazaretto on the island of San Simón , from where the pathology gradually spread throughout the Rías Bajas. At first, the outbreak only affected the lower classes, but it became increasingly virulent, and in 1854 it spread throughout La Coruña, causing three thousand deaths, according to an estimate by the doctor and mayor of La Coruña , Narciso Pérez Reoyo . The epidemic of 1855 affected large areas of the interior. This second outbreak is the most documented by the press of the time and the one with the greatest impact on the memory of those affected. It is possible to think that one out of every nineteen Spaniards was affected in the second epidemic. Although it was not the most deadly of the cholera outbreaks that occurred in Spain in the 19th century, it was devastating because of the consequences generated by its fear. All this despite the fact that the modes of transmission of the infection among the population were already beginning to be suspected and an incipient international network of health posts was being coordinated to provide regular information on the evolution and situation of the disease. In some cities, such as Madrid, the water communication and sanitation system was renewed, creating the Isabel II Canal . Epidemic outbreaks appeared successively in the Spanish provinces. This outbreak attacked with greater virulence the lower classes, especially the emerging working classes. Worldwide, the next pandemic emerged in 1863 and lasted until 1873. In 1865, cholera entered Spain through the port of Valencia , and the most affected provinces were Valencia , Palma de Mallorca , Gerona , León , Albacete , Huesca and Teruel . Dr. Antonio Fernández García did a commendable job of data collection. In Spain, political changes had occurred during the period from 1855 to 1865. In 1885, a great cholera epidemic affected about 5000 people, of whom 50 percent died, in the province of Jaén . It arrived preceded by some catastrophic phenomena, such as earthquakes and torrential rains, which created the ground for the epidemic to develop. It arrived from the Levant, through the province of Granada . In July 1885, it was already affecting towns such as Villacarrillo , Torreperogil , Cazorla , Arjonilla and Baeza . Although the first case was registered in Jaén on August 13, a month earlier there were deaths caused by enterocolitis , a diagnosis that can be interpreted as a euphemism for cholera when the disease is not declared. The total number of fatalities in the capital was 611, similar to that of the 1855 epidemic, but lower, percentage-wise; in any case, much higher than that of the national total. One of the last most virulent outbreaks occurred in 1893 in the Canary Islands. On October 11 of that year, the Italian ship Remo docked in Santa Cruz de Tenerife; it arrived from Rio Grande, on its way to Genoa . The isolation measures failed, which caused an epidemic of Asian-morbid-cholera to spread throughout the city and neighboring municipalities. Alarm spread to the other islands, which were immediately cut off from the island of Tenerife . Religious rogatory processions were carried out through the streets of the city, such as the Señor de las Tribulaciones (Lord of Tribulations). The attitude of the people of Santa Cruz during the epidemic earned the city the title of " Very Beneficent " and the Cross of First Class of the Spanish Order of Beneficence . It is estimated that 1,744 citizens were affected by the disease (8.84% of the population), of whom 382 died (21.90%). In the 20th century, the use of anti-cholera vaccines became regularized and the approach to the disease became known. There was progress in the development of vaccines and antibiotics. In spite of everything, there was an epidemic outbreak of cholera in the middle of Franco's regime , and the focus was located on the banks of the Jalón river ; this occurred in July 1971. Later, there was another outbreak in 1979. The administration took preventive measures to stop the advance of the disease, believing in the classic epidemic theories of the time. Dr. Pedro Castelló obtained from Fernando VII the authorization to send, in February 1832, a medical commission composed of Pedro María Rubio , Lorenzo Sánchez Núñez and Francisco Paula y Folch , in order to study the effects of cholera in cities such as Paris, Vienna and Munich. The result of their trip was the report sent from Berlin on May 31, 1833, which was not published until 1834. The appearance of the first outbreak in the peninsula from 1832 onwards was a question of time. Some of the measures were based on the creation of sanitary cordons , quarantines in the lazarettos , sectorized isolation of the population, and the establishment of hospitals. The hygienic conditions of some populated cities were improved, cleaning the streets more frequently. A Plan for the Cure of Morbid Cholera was published. The first controversy arose when the cords began to be applied to certain segments of the population: some doctors did not agree with the application of cords because of their dubious efficiency, besides the fact that they paralyzed economic activities. Some physicians, however, agreed with the measures and adopted them at their own discretion in the absence of a central health authority. At this time in the 19th century, cholera was considered an epidemic disease, not at all contagious, and therefore it was thought that the best course of action was to have good hygiene in order not to get it. The Plan for the Cure of Morbid Cholera gave numerous indications in this respect. It was mentioned that the main cause of cholera resided in the atmosphere itself. Prophylactic actions were carried out, such as taking the sale of fruits and vegetables out of the cities. Local Health Boards were established. The main pathogenic theories on morbidity were nervous, spasmodic, humoral and gastroenteric or inflammatory. One of the doctors who stood out in the first outbreaks was the hygienist Mateo Seoane Sobral , who published several articles on the evolution of pandemics in Europe, compiling the experiences of other countries in the treatment of the disease. In the same way, the precursor of Spanish epidemiology, Nicasio Landa y Álvarez de Carvallo carried out numerous statistical studies (medical topography, incidence rates, lethality rates, etc.) that allow studying the evolution of the disease today, especially those corresponding to the second outbreak of 1855.Nine months had passed since cholera had arrived in Paris , and a year and a half since it had arrived in England, and the Spanish and Portuguese authorities knew that it was only a matter of time before the first outbreak appeared on the peninsula. The first cases of the disease occurred in the city of Vigo , in January 1833. The first affected person was named Francisco Conde, and lived in the vicinity of the Vigo arsenal. In Barcelona, an outbreak occurred almost simultaneously. The outbreak started due to the landing of combat troops from the Portuguese War of Succession ; it is possible that they were responsible for their arrival in Spain, and it was in Andalusia where the most deadly cases occurred in the summer of that same year. The arrival of winter slowed the advance of the pandemic throughout the country, and when spring arrived, the disease reached Madrid in a second advance. From Vigo it spread to Pontevedra , and was isolated in that area of Galicia . Other stories mention that the disease came aboard the steamship Isabel la Católica , which came from Greece; in it, three sick people were traveling and were isolated in the corresponding lazaretto. However, days later cases appeared in Redondela , Tuy , Vigo, Pontevedra and in almost all the towns of the province. The outbreak in southern Spain was more virulent, and spread with great force due to environmental conditions, reaching Madrid , Toledo , Guadalajara , Soria , Avila , Burgos and Cuenca . In the capital, already in July 1834, the terror of the disease was of such intensity that there were massacres of friars , accused of causing the disease by poisoning the water. The event was reported in the local press. Everyone began to be suspected, the water carriers , the pharmacists, the doctors. The number of complaints of people suspected of contaminating the water multiplied. There was a third route of entry of the cholera of 1834 through the Mediterranean , the Balearic Islands and Tarragona . One of the causes was the French ship Triton , which had left Toulon with soldiers of the foreign legion on a long voyage that included Oran and Algiers . Cases of cholera on the ship began as soon as it left Toulon and, despite quarantining and sanitizing with lime, the ship spread cholera to the cities where it stopped, such as Tarragona and Roses . This first epidemic affected some 1,394 towns, the last province affected was Cáceres and the last town was Ceclavín . The epidemic lasted a total of one year, five months and twenty-two days. From the first outbreak almost 300,000 people were affected, three percent of the population.On November 19, 1853, the disease returned to the port of Vigo, through the steamship Isabel La Católica . The ship and its crew remained in quarantine in the lazaretto on the island of San Simón , from where the pathology gradually spread throughout the Rías Bajas. At first, the outbreak only affected the lower classes, but it became increasingly virulent, and in 1854 it spread throughout La Coruña, causing three thousand deaths, according to an estimate by the doctor and mayor of La Coruña , Narciso Pérez Reoyo . The epidemic of 1855 affected large areas of the interior. This second outbreak is the most documented by the press of the time and the one with the greatest impact on the memory of those affected. It is possible to think that one out of every nineteen Spaniards was affected in the second epidemic. Although it was not the most deadly of the cholera outbreaks that occurred in Spain in the 19th century, it was devastating because of the consequences generated by its fear. All this despite the fact that the modes of transmission of the infection among the population were already beginning to be suspected and an incipient international network of health posts was being coordinated to provide regular information on the evolution and situation of the disease. In some cities, such as Madrid, the water communication and sanitation system was renewed, creating the Isabel II Canal . Epidemic outbreaks appeared successively in the Spanish provinces. This outbreak attacked with greater virulence the lower classes, especially the emerging working classes. Worldwide, the next pandemic emerged in 1863 and lasted until 1873. In 1865, cholera entered Spain through the port of Valencia , and the most affected provinces were Valencia , Palma de Mallorca , Gerona , León , Albacete , Huesca and Teruel . Dr. Antonio Fernández García did a commendable job of data collection. In Spain, political changes had occurred during the period from 1855 to 1865. In 1885, a great cholera epidemic affected about 5000 people, of whom 50 percent died, in the province of Jaén . It arrived preceded by some catastrophic phenomena, such as earthquakes and torrential rains, which created the ground for the epidemic to develop. It arrived from the Levant, through the province of Granada . In July 1885, it was already affecting towns such as Villacarrillo , Torreperogil , Cazorla , Arjonilla and Baeza . Although the first case was registered in Jaén on August 13, a month earlier there were deaths caused by enterocolitis , a diagnosis that can be interpreted as a euphemism for cholera when the disease is not declared. The total number of fatalities in the capital was 611, similar to that of the 1855 epidemic, but lower, percentage-wise; in any case, much higher than that of the national total. One of the last most virulent outbreaks occurred in 1893 in the Canary Islands. On October 11 of that year, the Italian ship Remo docked in Santa Cruz de Tenerife; it arrived from Rio Grande, on its way to Genoa . The isolation measures failed, which caused an epidemic of Asian-morbid-cholera to spread throughout the city and neighboring municipalities. Alarm spread to the other islands, which were immediately cut off from the island of Tenerife . Religious rogatory processions were carried out through the streets of the city, such as the Señor de las Tribulaciones (Lord of Tribulations). The attitude of the people of Santa Cruz during the epidemic earned the city the title of " Very Beneficent " and the Cross of First Class of the Spanish Order of Beneficence . It is estimated that 1,744 citizens were affected by the disease (8.84% of the population), of whom 382 died (21.90%). In the 20th century, the use of anti-cholera vaccines became regularized and the approach to the disease became known. There was progress in the development of vaccines and antibiotics. In spite of everything, there was an epidemic outbreak of cholera in the middle of Franco's regime , and the focus was located on the banks of the Jalón river ; this occurred in July 1971. Later, there was another outbreak in 1979. The first outbreak of cholera was treated very discreetly by the Spanish press. For example, in the Madrid press the real situation was concealed until the outbreak reached the capital in 1834. It was feared that the disease would paralyze trade activities. The cholera pandemics, and especially that of 1885, have been extensively studied, including their therapeutic dimensions. The controversies about the possible scientific treatments, the discussions about the most effective ones, all of them were of great importance and created social alarm. It is worth mentioning Ferran 's vaccination and the national controversy unleashed around it. In any case, the social controversy was found in the frequent miraculous treatments. There was no shortage of healers who cured by means of prayers, magic words and signs. The multitude of ways of pretending to cure the disease depended fundamentally on the etiopathogenic doctrines held by the physicians of the time. As a prophylactic, quinine sulfate , camphor , and benzoic acid were recommended; other remedies were cinnabar cigar, a mineral rich in mercury , and charcoal smoke. The level of destitution in the cities was high; since the end of the 18th century, the number of people in such conditions in the big cities did not stop growing. It was this social group that led popular revolts, some directed against the Church and others against other hierarchical bodies of power. Riots broke out in the big cities. Their lifestyle, lacking hygiene, food and basic means, made them one of the targets of the disease. Cities and towns became isolated and suffered from access controls. Walled cities used the walls as a "barrier of access". Suspects were taken to the lazarettos . The Carlist Wars , with their consequent movement of troops, contributed to the spread of cholera epidemics. The terror caused by the disease caused the cholera outbreak of 1865 to empty cities such as Madrid and Burgos . A large percentage of the population was displaced, leaving their businesses abandoned and the cities depopulated. The effect on the economy was felt in subsequent decades. After each outbreak, the fields were abandoned and were followed by periods of famine that affected large groups of the population. Prior to these epidemics, cemeteries in Spain were located in the center of cities, sometimes near the hospitals themselves, and sometimes people were buried inside churches. The transfer of the cemeteries from the center of the towns to the outskirts was due precisely to the number of deaths. In many cases, cemeteries were moved from within the city walls to outside the city walls. In many cemeteries, "family" graves were kept open, waiting for new deaths among close relatives to cover them when they were full. After the first outbreaks, rare was the city that did not have cemeteries located "on the outskirts"; at present, some of the popular cemeteries are located on the outskirts, and date from the beginning of the 20th century.

Wiki

Cholera

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

Sambhu Nath De

Sambhunath De FRS FRSM ; (1 February 1915 – 15 April 1985) was an Indian medical scientist and researcher, who discovered the cholera toxin , the animal model of cholera , and successfully demonstrated the method of transmission of cholera pathogen Vibrio cholerae . Shambhu Nath De was born in Hooghly District , West Bengal, India. His father Mr Dasarathi De was a not so successful businessman. Supported by his uncle Asutosh De, De completed the Matriculation examination with distinction from Garbati High School that helped him to get the District scholarship as well as to pursue further education in Hooghly Mohsin College , which was then affiliated with the prestigious University of Calcutta . His higher education was supported by Kestodhan Seth , who identified De as an extraordinary student. De passed his M.B. examination in 1939 from Calcutta Medical College and completed a Diploma in Tropical Medicine (DTM) in 1942. Soon after graduation he joined Calcutta Medical College as a Demonstrator of Pathology and initiated his research under Professor B. P. Tribedi. In 1947, De joined as a PhD student under Sir Roy Cameron at the Department of Morbid Anatomy, University College Hospital Medical School , London, and obtained his PhD degree in Pathology in 1949. After his return, De worked on pathogenesis of cholera and started publishing his findings. In 1955, De became the Head of Pathology and Bacteriology Division of the Calcutta Medical College, which he continued until his retirement. De published more than 30 research papers and has written an excellent monograph on cholera and its pathogenesis. De made significant contributions to our recent understanding of cholera and related diarrhoeal diseases and set a permanent milestone in the modern view of diseases caused by bacterial exotoxins. Followed by the discovery of Vibrio cholerae in 1884 by Robert Koch, many works have been carried out all over the world to answer many questions related with its pathogenesis and mode of transmission in causing outbreaks. The seminal works of De in Calcutta (now, Kolkata), during 1950–60 breached several qualms pertaining to the enteric toxin produced by bacteria including V. cholerae and Escherichia coli. Three of his works viz., ligated intestinal loop method (which was a reinvention of Violle and Crendiropoulo method in 1915, but De was unaware of this work and made an independent discovery) for studying cholera in rabbit model; ileal loop model to demonstrate the association of some strains of E. coli with diarrhoea and lastly but most importantly is his discovery of cholera toxin in 1959 in the cell-free culture filtrate of V. cholerae that stimulated a specific cellular response. Says Eugene Garfield, founder-editor of Current Contents and Science Citation Index and publisher of The Scientist, in his 1986 tribute to De: In 1959 De was the first to demonstrate that cholera bacteria secrete enterotoxin. This discovery eventually promoted research to find a treatment aimed directly at neutralising the cholera enterotoxin. De's paper "Enterotoxicity of bacteria-free culture-filtrate of Vibrio cholerae," while initially unrecognised, today is considered a milestone in the history of cholera research. Biochemist W.E. van Heyningen, professor emeritus, University of Oxford, UK, and John R. Seal, former scientific director, National Institute of Allergy and Infectious Diseases, Bethesda, note that De's paper "deserves to go down as a classic in the history of cholera, and, indeed, as later developments have shown, in the history of cellular physiology and biochemistry." Thanks to De's discovery of the cholera enterotoxin, research has been redirected to find a vaccine that will spark the immune system to fight the enterotoxin specifically, rather than the bacteria. De and colleagues also published highly cited pioneering studies on V.cholerae action on the intestinal membrane. , , The 1953 paper "An experimental study of the mechanism of action of Vibrio cholerae on the intestinal mucous membrane" is De's most-cited paper, cited 340 times until August 1986. De's most-cited paper has been core to cholera research fronts for many years, especially research fronts on "E. coli and Vibrio cholerae enterotoxin: detection, characterization, and role of adherence" and "Characterization of cholera enterotoxin and other enterotoxins". As noted by John Craig, State University of New York Health Science Center at Brooklyn, De's work was truly creative and novel, and it "forever altered our concepts surrounding the pathogenesis of secretory diarrhoea." These famous findings came out from the work he carried out at the Nilratan Sircar Medical College, Calcutta Medical College and Bose Institute, Kolkata in extremely modest laboratory settings. Using research methodology that was very simple, easy to perform and inexpensive, he set the highest standards of excellence in novel experimental design and execution. In the words of Nobel Laureate Prof. Joshua Lederberg, "De's clinical observations led him to the bold thought that dehydration was a sufficient cause of pathology of cholera, that the cholera toxin can kill 'merely' by stimulating the secretion of water into the bowel". Thus, the oral rehydration therapy (ORT) for replenishing the massive fluid loss in cholera patients, has saved innumerable lives, should be considered as a direct outcome of De's discovery of cholera toxin. His findings on exotoxins set the stage for the modern views of diseases caused by toxin producing bacteria, helped in the purification of cholera and heat-labile (LT) enterotoxins produced by V. cholerae and E. coli, respectively, and in the development of series of cholera and enterotoxigenic E. coli (in short ETEC strains) vaccines.De retired in 1973 from the Calcutta Medical College at the age of 58. After his retirement, he showed no interest in higher positions but continued his research at the Bose Institute, Calcutta. De's desire to purify the cholera toxin did not progress any further as the protein purification technology was not well established in his research settings. During his time of research, De worked with hypertoxin-producing classical strains of V. cholerae O1, which was abruptly replaced by El Tor biotype [producing less cholera toxin] in Calcutta from 1963. This new development was another reason why De could not continue his research on purification of cholera toxin. In 1978, the Nobel Foundation invited De to participate in the 43rd Nobel Symposium on Cholera and Related Diarrhoeas. De died on 15 April 1985 at the age of 70.But for Eugene Garfield's 1986 tribute to De in Current Contents,6 De's great contributions to cholera research would have continued to remain unknown to many even in India. A special issue of the journal Current Science (Bangalore, India) was published in 1990 in honour of De, to which several eminent scientists of national and international repute contributed. In the words of Dr S Sriramachari, former director of the Institute of Pathology and additional director general of the Indian Council of Medical Research, New Delhi, De's contributions stand out as a pinnacle of excellence in our understanding of the pathogenesis of cholera. Nobel laureate Prof. Joshua Lederberg had nominated De for the Nobel Prize more than once. Said Lederberg, "our appreciation of De must then extend beyond the humanitarian consequences of his discovery. . . he is also an examplar and inspiration for a boldness of challenge to the established wisdom, a style of thought that should be more aggressively taught by example as well as precept." And yet De was never elected a fellow of any Indian academy and never received any major award. Indeed as Professor Padmanabhan Balaram pointed out in an editorial in Current Science, "De died in 1985 unhonoured and unsung in India's scientific circles. That De received no major award in India during his lifetime and our Academies did not see it fit to elect him to their Fellowships must rank as one of the most glaring omissions of our time. De emerges, in retrospect, as a modest self-effacing scientist driven by inner compulsions to grapple with a major scientific problem of the time. His choice of cholera as his field of interest was remarkably appropriate to his setting. To this problem De brought a wonderfully thoughtful approach, together with deep intuition, enabling him to make the long-awaited breakthrough in the field. De's heroic story of persistence, dedication and achievement should serve as an inspiration to the many who are increasingly bewildered by the current fashion of mega projects, surrounded by fanfare and publicity and most often surprisingly little discernible scientific output."

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/Chicago_1885_cholera_epidemic_myth/html

Chicago 1885 cholera epidemic myth

The Chicago 1885 cholera epidemic myth is a persistent urban legend , stating that 90,000 people in Chicago died of typhoid fever and cholera in 1885. Although the story is widely reported, these deaths did not occur. Lake Michigan was the source of Chicago's drinking water. During a tremendous storm in 1885, the rainfall washed refuse from the Chicago River far out into the lake. Citizens feared that sewage run-off from the storm would reach the intake cribs of the Chicago lake tunnels (built in 1866 and 1874) and pollute the city's drinking water. According to the legend, typhoid, cholera and other waterborne diseases from the contaminated drinking water killed up to 90,000 people. The Chicago Sanitary District (now The Metropolitan Water Reclamation District ) was said [ by whom? ] to have been created by the Illinois legislature in 1889 in response to a terrible epidemic which killed thousands of residents of this fledgling city. However, analysis of the deaths in Chicago shows no deaths from cholera and only a slight rise in typhoid deaths. In fact, no cholera outbreaks had occurred in Chicago since the 1860s. Typhoid deaths never exceeded 1,000 in any year in the 1880s. The supposed 90,000 deaths would have represented 12% of the city's entire population and would have left numerous public records as well as newspaper accounts. Libby Hill, researching her book The Chicago River: A Natural and Unnatural History , found no newspaper or mortality records and, at her prompting, the Chicago Tribune issued a retraction (on September 29, 2005) of the three recent instances where they had mentioned the epidemic. An outbreak of cholera in 1849 killed 678 persons, 2.9 percent of the city's population, and an 1854 outbreak killed 1,424 people. Another cholera epidemic hit the city in 1866 and 1867. In the late 19th century, typhoid fever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst year was 1891, when the typhoid death rate was 174 per 100,000 persons.

Wiki

Cholera

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

VIPoma

A VIPoma or vipoma ( / v ɪ ˈ p oʊ m ə / ) is a rare endocrine tumor that overproduces vasoactive intestinal peptide (thus VIP + -oma ). The incidence is about 1 per 10,000,000 per year. VIPomas usually (about 90%) originate from the non-β islet cells of the pancreas . They are sometimes associated with multiple endocrine neoplasia type 1 . Roughly 50–75% of VIPomas are malignant , but even when they are benign , they are problematic because they tend to cause a specific syndrome : the massive amounts of VIP cause a syndrome of profound and chronic watery diarrhea and resultant dehydration , hypokalemia , achlorhydria , acidosis, flushing and hypotension (from vasodilation ), hypercalcemia , and hyperglycemia . This syndrome is called Verner–Morrison syndrome ( VMS ), WDHA syndrome (from watery diarrhea–hypokalemia–achlorhydria), or pancreatic cholera syndrome ( PCS ). The eponym reflects the physicians who first described the syndrome. The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration . Half of the patients have relatively constant diarrhea while the rest have alternating periods of severe and moderate diarrhea . One third have diarrhea < 1yr before diagnosis, but in 25%, diarrhea is present for 5 yr or more before diagnosis. Lethargy , muscle weakness, nausea , vomiting and crampy abdominal pain are frequent symptoms. Hypokalemia and impaired glucose tolerance occur in < 50% of patients. Achlorhydria is also a feature. During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely. Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor , which is usually metastatic at presentation. Tests include: Blood chemistry tests (basic or comprehensive metabolic panel) CT scan of the abdomen MRI of the abdomen Stool examination for the cause of diarrhea and electrolyte levels Vasoactive intestinal peptide (VIP) level in the blood The first goal of treatment is to correct dehydration. Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea. The next goal is to slow the diarrhea. Some medications can help control diarrhea. Octreotide , which is a human-made form of the natural hormone somatostatin, blocks the action of VIP. [ citation needed ] The best chance for a cure is surgery to remove the tumor. If the tumor has not spread to other organs, surgery can often cure the condition. [ citation needed ] For metastatic disease, peptide receptor radionuclide therapy (PRRT) can be highly effective. This treatment involves attaching a radionuclide (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a novel way to deliver high doses of beta radiation to kill tumours. Some people seem to respond to a combination chemo called capecitabine and temozolomide but there is no report that it totally cured people of VIPoma. [ citation needed ]Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured. [ citation needed ]

Wiki

Cholera

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

Cholera Street

28 November 1997 ( 1997-11-28 ) Cholera Street (Original Turkish title: Ağır Roman , literally meaning "Heavy Romani ") is a 1997 Turkish film directed by Mustafa Altıoklar , adapted from Metin Kaçan 's best selling novel Ağır Roman .The film is set in a rundown, crime ridden neighborhood of Istanbul dubbed "Cholera Street" (Kolera Sokağı). Salih is a mechanic and son of a respected barber Ali. A woman Tina arrives at Cholera street where she takes up residence and works as a prostitute. Deniz is a gangster who gives himself the nickname "Reiss" ("Chief"), tries to take control of the neighbourhood through intimidation. After Reiss takes over a horse stable and causes the suicide of the owner, Arap Sado (a close friend of Salih) challenges Reiss to a knife duel and after defeating him, demands that he leave the neighborhood. One night, a prostitute is murdered with her genitals cut out, and this causes fears of a serial killer on the loose called the "Kolera Canavarı" ("Cholera Monster"). Sado is targeted by Reis' men in a drive by shooting and he dies in Salih's arms after giving him his prized pocket knife. With Sado dead, Reiss opens a casino and seeks to dominate the neighbour. At the opening of Sado's bust, Salih and Reiss clash on the street, during which the public defies Reis and side with Salih. Tina invites Salih to her home that night, after which Tina and Salih become a couple. Salih gets Tina to promise that she will give up prostitution, but this causes hardship because they now have no income. The "Cholera Monster" strikes again and murders "Puma" Zehra (the madame of a brothel) on Salih's watch. Reiss takes advantage of the situation, declaring himself protector of the neighborhood and turning the public against Salih. Salih becomes suspicious after Tina returns late and confronts her about it. Tina tries to justify her returning to prostitution by saying that they needed money to survive. While Tina runs away from an angry Salih, she is attacked by the "Cholera Monster" but Salih manages save her and subdue him. Tina's former pimp Nihat is distraught at the loss of his livelihood and his treatment at hands of Tina. He goes to Reis who takes him in and draws up a scheme to get rid of Salih. After being provoked by Reis, Nihat attacks Tina and slashes her cheek with a blade at a wedding. Salih runs him down, kills him and cuts his cheek off with a knife. The corrupt police chief who is under Reis' pay, arrests Salih and tries to force him to confess to the murder. Reis approaches Tina and makes a deal that he will get Salih released if she gives herself to him. When Salih returns home, he finds Reiss and Tina together in bed; he becomes distraught and cuts himself and bleeds to death. As an act of revenge, Tina gets into Reis' car and blows it up with Reiss and herself in it.Ağır Roman won 3 awards at the 35th Antalya Film Festival : "Best Supporting Actor" (Mustafa Uğurlu), "Best Supporting Actress" (Sevda Ferdağ) and "Best Art Director" (Mustafa Ziya Ülkenciler). Additionally, Okan Bayülgen was awarded "Best Actor" at the 3rd Sadri Alışık awards.

Wiki

Cholera

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

World War I

and others ... Military dead: Over 5,525,000 Civilian dead: Over 4,000,000 Total dead: Over 9,000,000 ... further details Military dead: Over 4,386,000 Civilian dead: Over 3,700,000 Total dead: Over 8,000,000 ... further details World War I , commonly known as The Great War [lower-alpha 10] or as the First World War (28 July 1914 – 11 November 1918) was a global conflict between two coalitions: the Allies and the Central Powers . Fighting took place throughout Europe , the Middle East , Africa , the Pacific , and parts of Asia . One of the deadliest wars in history , it resulted in an estimated 9 million soldiers dead and 23 million wounded, plus up to 8 million civilian deaths from numerous causes including genocide . The movement of large numbers of troops and civilians during the war was a major factor in spreading the 1918 Spanish flu pandemic. Increasing diplomatic tensions between the European great powers reached a breaking point on 28 June 1914, when a Bosnian Serb named Gavrilo Princip assassinated Archduke Franz Ferdinand , heir to the Austro-Hungarian throne. Austria-Hungary held Serbia responsible, and declared war on 28 July. Russia came to Serbia's defence, and by 4 August, Germany , France , and Britain were drawn into the war, with the Ottoman Empire joining in November of the same year. Germany's strategy in 1914 was to first defeat France, then transfer forces to the Russian front. However, this failed , and by the end of 1914, the Western Front consisted of a continuous line of trenches stretching from the English Channel to Switzerland . The Eastern Front was more dynamic, but neither side could gain a decisive advantage, despite costly offensives. As the war expanded to more fronts, Bulgaria , Italy , Romania , Greece and others joined in from 1915 onward. In early 1917, the United States entered the war on the Allies' side, and later the same year, the Bolsheviks seized power in the Russian October Revolution , making peace with the Central Powers in early 1918. Germany launched an offensive in the west in March 1918, and despite initial successes, it left the German Army exhausted and demoralised. A successful Allied counter-offensive later that year caused a collapse of the German frontline. By the end of 1918, Bulgaria, the Ottoman Empire and Austria-Hungary agreed to armistices with the Allies, leaving Germany isolated. Facing revolution at home and with his army on the verge of mutiny, Kaiser Wilhelm II abdicated on 9 November. The fighting ended with the Armistice of 11 November 1918 , while the subsequent Paris Peace Conference imposed various settlements on the defeated powers, notably the Treaty of Versailles . The dissolution of the Russian, German, Austro-Hungarian, and Ottoman Empires resulted in the creation of new independent states, including Poland , Finland , Czechoslovakia , and Yugoslavia . The inability to manage post-war instability contributed to the outbreak of World War II in September 1939.The first recorded use of the term First World War was in September 1914 by German biologist and philosopher Ernst Haeckel who stated, "There is no doubt that the course and character of the feared 'European War' ... will become the first world war in the full sense of the word." It was later used as a title for his 1920 memoirs by Lt-Col. Charles à Court Repington . Before World War II , the events of 1914–1918 were generally known as the Great War or simply the World War . In August 1914, the magazine The Independent wrote "This is the Great War. It names itself". In October 1914, the Canadian magazine Maclean's similarly wrote, "Some wars name themselves. This is the Great War." Contemporary Europeans also referred to it as " the war to end war " and it was also described as "the war to end all wars" due to their perception of its unparalleled scale, devastation, and loss of life. For much of the 19th century, the major European powers maintained a tenuous balance of power , known as the Concert of Europe . After 1848, this was challenged by Britain's withdrawal into so-called splendid isolation , the decline of the Ottoman Empire , New Imperialism , and the rise of Prussia under Otto von Bismarck . The 1866 Austro-Prussian War established Prussian hegemony in German states, while victory in the 1870–1871 Franco-Prussian War allowed Bismarck to consolidate a German Empire under Prussian leadership. Avenging the defeat of 1871, or revanchism , and recovering the provinces of Alsace-Lorraine became an obsession of French policy and public opinion for the following few years, yet since the 1880s this concern was eclipsed by the conquest of a vast colonial empire, and had disappeared from the programs of all French political parties as utterly unrealistic. To isolate France and avoid a war on two fronts, Bismarck negotiated the League of the Three Emperors between Austria-Hungary , Russia and Germany. After Russian victory in the 1877–1878 Russo-Turkish War , the League was dissolved due to Austrian concerns over Russian influence in the Balkans , an area they considered to be of vital strategic interest. Germany and Austria-Hungary then formed the 1879 Dual Alliance , which became the Triple Alliance when Italy joined in 1882. For Bismarck, the purpose of these agreements was to isolate France by ensuring the three Empires resolve any disputes between themselves; when this was threatened in 1880 by British and French attempts to negotiate directly with Russia, he reformed the League in 1881, which was renewed in 1883 and 1885. After the agreement lapsed in 1887, he replaced it with the Reinsurance Treaty , a secret agreement between Germany and Russia to remain neutral if either were attacked by France or Austria-Hungary. Bismarck viewed peace with Russia as the foundation of German foreign policy but after becoming Kaiser in 1890, Wilhelm II forced him to retire and was persuaded not to renew the Reinsurance Treaty by his new Chancellor , Leo von Caprivi . This provided France an opportunity to counteract the Triple Alliance by signing the Franco-Russian Alliance in 1894, followed by the 1904 Entente Cordiale with Britain. The Triple Entente was completed by the 1907 Anglo-Russian Convention . While these were not formal alliances, by settling long-standing colonial disputes in Asia and Africa, the notion of British entry into any future conflict involving France or Russia became a possibility. British and Russian support for France against Germany during the Agadir Crisis in 1911 reinforced their relationship, increasing Anglo-German estrangement. German industrial strength and production had significantly increased after 1871, driven by the creation of a unified Reich, French indemnity payments, and the annexation of Alsace-Lorraine . Backed by Wilhelm II, Admiral Alfred von Tirpitz sought to use this growth in economic power to build a Kaiserliche Marine , or Imperial German Navy , which could compete with the British Royal Navy for naval supremacy. His thinking was influenced by US naval strategist Alfred Thayer Mahan , who had argued that possession of a blue-water navy was vital for global power projection; Tirpitz had his books translated into German, while Wilhelm made them required reading for his advisors and senior military personnel. However, it was also an emotional decision, driven by Wilhelm's simultaneous admiration for the Royal Navy and desire to surpass it. Bismarck thought that the British would not interfere in Europe, as long as its maritime supremacy remained secure, but his dismissal in 1890 led to a change in policy and an Anglo-German naval arms race began. Despite the vast sums spent by Tirpitz, the launch of HMS Dreadnought in 1906 gave the British a technological advantage over their German rivals. Ultimately, the race diverted huge resources into creating a German navy large enough to antagonise Britain, but not defeat it; in 1911, Chancellor Theobald von Bethmann Hollweg acknowledged defeat, leading to the Rüstungswende or 'armaments turning point', when he switched expenditure from the navy to the army. This decision was not driven by a reduction in political tensions but by German concern over Russia's quick recovery from its defeat in the Russo-Japanese War and subsequent 1905 Russian Revolution that same year. Economic reforms, backed by French funding, led to a significant post-1908 expansion of railways and transportation infrastructure, particularly in its western border regions. Since Germany and Austria-Hungary relied on faster mobilisation to compensate for their numerical inferiority compared to Russia , the threat posed by the closing of this gap was more important than competing with the Royal Navy. After Germany expanded its standing army by 170,000 troops in 1913, France extended compulsory military service from two to three years; similar measures were taken by the Balkan powers and Italy, which led to increased expenditure by the Ottomans and Austria-Hungary. Absolute figures are difficult to calculate due to differences in categorising expenditure since they often omit civilian infrastructure projects like railways which also had logistical importance and military use. It is known, however, that from 1908 to 1913, military spending by the six major European powers increased by over 50% in real terms. The years before 1914 were marked by a series of crises in the Balkans, as other powers sought to benefit from the Ottoman decline. While Pan-Slavic and Orthodox Russia considered itself the protector of Serbia and other Slav states, they preferred the strategically vital Bosporus straits to be controlled by a weak Ottoman government, rather than an ambitious Slav power like Bulgaria . Since Russia had its ambitions in northeastern Anatolia , while their clients had overlapping claims in the Balkans, balancing these divided Russian policy-makers and added to regional instability. Austrian statesmen viewed the Balkans as essential for the continued existence of their Empire and saw Serbian expansion as a direct threat. The 1908–1909 Bosnian Crisis began when Austria annexed the former Ottoman territory of Bosnia and Herzegovina , which it had occupied since 1878. Timed to coincide with the Bulgarian Declaration of Independence from the Ottoman Empire, this unilateral action was denounced by the European powers, but accepted as there was no consensus on how to resolve the situation. Some historians see this as a significant escalation, ending any chance of Austria cooperating with Russia in the Balkans, while also damaging diplomatic relations between Serbia and Italy, both of whom had their expansionist ambitions in the region. Tensions increased after the 1911–1912 Italo-Turkish War demonstrated Ottoman weakness and led to the formation of the Balkan League , an alliance of Serbia, Bulgaria, Montenegro , and Greece . The League quickly overran most of the Ottomans' territory in the Balkans during the 1912–1913 First Balkan War , much to the surprise of outside observers. The Serbian capture of ports on the Adriatic resulted in partial Austrian mobilisation, starting on 21 November 1912, including units along the Russian border in Galicia . In a meeting the next day, the Russian government decided not to mobilise in response, unwilling to precipitate a war for which they were not as of yet prepared to handle. The Great Powers sought to re-assert control through the 1913 Treaty of London , which had created an independent Albania while enlarging the territories of Bulgaria, Serbia, Montenegro and Greece. However, disputes between the victors sparked the 33-day Second Balkan War , when Bulgaria attacked Serbia and Greece on 16 June 1913; it was defeated, losing most of Macedonia to Serbia and Greece, and Southern Dobruja to Romania. The result was that even countries which benefited from the Balkan Wars, such as Serbia and Greece, felt cheated of their "rightful gains", while for Austria it demonstrated the apparent indifference with which other powers viewed their concerns, including Germany. This complex mix of resentment, nationalism and insecurity helps explain why the pre-1914 Balkans became known as the " powder keg of Europe ". For much of the 19th century, the major European powers maintained a tenuous balance of power , known as the Concert of Europe . After 1848, this was challenged by Britain's withdrawal into so-called splendid isolation , the decline of the Ottoman Empire , New Imperialism , and the rise of Prussia under Otto von Bismarck . The 1866 Austro-Prussian War established Prussian hegemony in German states, while victory in the 1870–1871 Franco-Prussian War allowed Bismarck to consolidate a German Empire under Prussian leadership. Avenging the defeat of 1871, or revanchism , and recovering the provinces of Alsace-Lorraine became an obsession of French policy and public opinion for the following few years, yet since the 1880s this concern was eclipsed by the conquest of a vast colonial empire, and had disappeared from the programs of all French political parties as utterly unrealistic. To isolate France and avoid a war on two fronts, Bismarck negotiated the League of the Three Emperors between Austria-Hungary , Russia and Germany. After Russian victory in the 1877–1878 Russo-Turkish War , the League was dissolved due to Austrian concerns over Russian influence in the Balkans , an area they considered to be of vital strategic interest. Germany and Austria-Hungary then formed the 1879 Dual Alliance , which became the Triple Alliance when Italy joined in 1882. For Bismarck, the purpose of these agreements was to isolate France by ensuring the three Empires resolve any disputes between themselves; when this was threatened in 1880 by British and French attempts to negotiate directly with Russia, he reformed the League in 1881, which was renewed in 1883 and 1885. After the agreement lapsed in 1887, he replaced it with the Reinsurance Treaty , a secret agreement between Germany and Russia to remain neutral if either were attacked by France or Austria-Hungary. Bismarck viewed peace with Russia as the foundation of German foreign policy but after becoming Kaiser in 1890, Wilhelm II forced him to retire and was persuaded not to renew the Reinsurance Treaty by his new Chancellor , Leo von Caprivi . This provided France an opportunity to counteract the Triple Alliance by signing the Franco-Russian Alliance in 1894, followed by the 1904 Entente Cordiale with Britain. The Triple Entente was completed by the 1907 Anglo-Russian Convention . While these were not formal alliances, by settling long-standing colonial disputes in Asia and Africa, the notion of British entry into any future conflict involving France or Russia became a possibility. British and Russian support for France against Germany during the Agadir Crisis in 1911 reinforced their relationship, increasing Anglo-German estrangement. German industrial strength and production had significantly increased after 1871, driven by the creation of a unified Reich, French indemnity payments, and the annexation of Alsace-Lorraine . Backed by Wilhelm II, Admiral Alfred von Tirpitz sought to use this growth in economic power to build a Kaiserliche Marine , or Imperial German Navy , which could compete with the British Royal Navy for naval supremacy. His thinking was influenced by US naval strategist Alfred Thayer Mahan , who had argued that possession of a blue-water navy was vital for global power projection; Tirpitz had his books translated into German, while Wilhelm made them required reading for his advisors and senior military personnel. However, it was also an emotional decision, driven by Wilhelm's simultaneous admiration for the Royal Navy and desire to surpass it. Bismarck thought that the British would not interfere in Europe, as long as its maritime supremacy remained secure, but his dismissal in 1890 led to a change in policy and an Anglo-German naval arms race began. Despite the vast sums spent by Tirpitz, the launch of HMS Dreadnought in 1906 gave the British a technological advantage over their German rivals. Ultimately, the race diverted huge resources into creating a German navy large enough to antagonise Britain, but not defeat it; in 1911, Chancellor Theobald von Bethmann Hollweg acknowledged defeat, leading to the Rüstungswende or 'armaments turning point', when he switched expenditure from the navy to the army. This decision was not driven by a reduction in political tensions but by German concern over Russia's quick recovery from its defeat in the Russo-Japanese War and subsequent 1905 Russian Revolution that same year. Economic reforms, backed by French funding, led to a significant post-1908 expansion of railways and transportation infrastructure, particularly in its western border regions. Since Germany and Austria-Hungary relied on faster mobilisation to compensate for their numerical inferiority compared to Russia , the threat posed by the closing of this gap was more important than competing with the Royal Navy. After Germany expanded its standing army by 170,000 troops in 1913, France extended compulsory military service from two to three years; similar measures were taken by the Balkan powers and Italy, which led to increased expenditure by the Ottomans and Austria-Hungary. Absolute figures are difficult to calculate due to differences in categorising expenditure since they often omit civilian infrastructure projects like railways which also had logistical importance and military use. It is known, however, that from 1908 to 1913, military spending by the six major European powers increased by over 50% in real terms. The years before 1914 were marked by a series of crises in the Balkans, as other powers sought to benefit from the Ottoman decline. While Pan-Slavic and Orthodox Russia considered itself the protector of Serbia and other Slav states, they preferred the strategically vital Bosporus straits to be controlled by a weak Ottoman government, rather than an ambitious Slav power like Bulgaria . Since Russia had its ambitions in northeastern Anatolia , while their clients had overlapping claims in the Balkans, balancing these divided Russian policy-makers and added to regional instability. Austrian statesmen viewed the Balkans as essential for the continued existence of their Empire and saw Serbian expansion as a direct threat. The 1908–1909 Bosnian Crisis began when Austria annexed the former Ottoman territory of Bosnia and Herzegovina , which it had occupied since 1878. Timed to coincide with the Bulgarian Declaration of Independence from the Ottoman Empire, this unilateral action was denounced by the European powers, but accepted as there was no consensus on how to resolve the situation. Some historians see this as a significant escalation, ending any chance of Austria cooperating with Russia in the Balkans, while also damaging diplomatic relations between Serbia and Italy, both of whom had their expansionist ambitions in the region. Tensions increased after the 1911–1912 Italo-Turkish War demonstrated Ottoman weakness and led to the formation of the Balkan League , an alliance of Serbia, Bulgaria, Montenegro , and Greece . The League quickly overran most of the Ottomans' territory in the Balkans during the 1912–1913 First Balkan War , much to the surprise of outside observers. The Serbian capture of ports on the Adriatic resulted in partial Austrian mobilisation, starting on 21 November 1912, including units along the Russian border in Galicia . In a meeting the next day, the Russian government decided not to mobilise in response, unwilling to precipitate a war for which they were not as of yet prepared to handle. The Great Powers sought to re-assert control through the 1913 Treaty of London , which had created an independent Albania while enlarging the territories of Bulgaria, Serbia, Montenegro and Greece. However, disputes between the victors sparked the 33-day Second Balkan War , when Bulgaria attacked Serbia and Greece on 16 June 1913; it was defeated, losing most of Macedonia to Serbia and Greece, and Southern Dobruja to Romania. The result was that even countries which benefited from the Balkan Wars, such as Serbia and Greece, felt cheated of their "rightful gains", while for Austria it demonstrated the apparent indifference with which other powers viewed their concerns, including Germany. This complex mix of resentment, nationalism and insecurity helps explain why the pre-1914 Balkans became known as the " powder keg of Europe ". In the summer of 1914, the sovereigns of Europe were woven together by treaties, alliances, as well as secret agreements. The Triple Alliance (1882) encompassed the German Empire, Austria , and Italy. On 28 June 1914, Archduke Franz Ferdinand of Austria , heir presumptive to Emperor Franz Joseph I of Austria , visited Sarajevo , the capital of the recently annexed Bosnia and Herzegovina . Cvjetko Popović , Gavrilo Princip , Nedeljko Čabrinović , Trifko Grabež , and Vaso Čubrilović ( Bosnian Serbs ) and Muhamed Mehmedbašić (from the Bosniaks community), from the movement known as Young Bosnia , took up positions along the route taken by the Archduke's motorcade, to assassinate him. Supplied with arms by extremists within the Serbian Black Hand intelligence organisation, they hoped his death would free Bosnia from Austrian rule, although there was little agreement on what would replace it. Nedeljko Čabrinović threw a grenade at the Archduke's car and injured two of his aides, who were taken to hospital while the convoy carried on. The other assassins were also unsuccessful but, an hour later, as Ferdinand was returning from visiting the injured officers, his car took a wrong turn into a street where Gavrilo Princip was standing. He fired two pistol shots, fatally wounding Ferdinand and his wife Sophie . Although Emperor Franz Joseph was shocked by the incident, political and personal differences meant the two men were not close; allegedly, his first reported comment was "A higher power has re-established the order which I, alas, could not preserve". According to historian Zbyněk Zeman , in Vienna "the event almost failed to make any impression whatsoever. On 28 and 29 June, the crowds listened to music and drank wine, as if nothing had happened." Nevertheless, the impact of the murder of the heir to the throne was significant, and has been described by historian Christopher Clark as a " 9/11 effect , a terrorist event charged with historic meaning, transforming the political chemistry in Vienna". Austro-Hungarian authorities encouraged subsequent anti-Serb riots in Sarajevo , in which Bosnian Croats and Bosniaks killed two Bosnian Serbs and damaged numerous Serb-owned buildings. Violent actions against ethnic Serbs were also organised outside Sarajevo, in other cities in Austro-Hungarian-controlled Bosnia and Herzegovina, Croatia and Slovenia. Austro-Hungarian authorities in Bosnia and Herzegovina imprisoned and extradited approximately 5,500 prominent Serbs, 700 to 2,200 of whom died in prison. A further 460 Serbs were sentenced to death. A predominantly Bosniak special militia known as the Schutzkorps was established, and carried out the persecution of Serbs. The assassination initiated the July Crisis , a month of diplomatic manoeuvring between Austria-Hungary, Germany, Russia, France and Britain. Believing that Serbian intelligence helped organise Franz Ferdinand's murder, Austrian officials wanted to use the opportunity to end their interference in Bosnia and saw war as the best way of achieving this. However, the Foreign Ministry had no solid proof of Serbian involvement and a dossier used to make its case contained multiple errors. On 23 July, Austria delivered an ultimatum to Serbia, listing ten demands made intentionally unacceptable to provide an excuse for starting hostilities. Serbia ordered general mobilization on 25 July, but accepted all the terms, except for those empowering Austrian representatives to suppress "subversive elements" inside Serbia, and take part in the investigation and trial of Serbians linked to the assassination. Claiming this amounted to rejection, Austria broke off diplomatic relations and ordered partial mobilisation the next day; on 28 July, they declared war on Serbia and began shelling Belgrade . Having initiated war preparations on 25 July, Russia now ordered general mobilization in support of Serbia on 30th. Anxious to ensure backing from the SPD political opposition by presenting Russia as the aggressor, German Chancellor Bethmann Hollweg delayed the commencement of war preparations until 31 July. That afternoon, the Russian government were handed a note requiring them to "cease all war measures against Germany and Austria-Hungary" within 12 hours. A further German demand for neutrality was refused by the French who ordered general mobilization but delayed declaring war. The German General Staff had long assumed they faced a war on two fronts; the Schlieffen Plan envisaged using 80% of the army to defeat France, then switch to Russia. Since this required them to move quickly, mobilization orders were issued that afternoon. At a meeting on 29 July, the British cabinet had narrowly decided its obligations to Belgium under the 1839 Treaty of London did not require it to oppose a German invasion with military force. However, this was largely driven by Prime Minister Asquith 's desire to maintain unity; he and his senior Cabinet ministers were already committed to supporting France, the Royal Navy had been mobilised, and public opinion was strongly in favour of intervention. On 31 July, Britain sent notes to Germany and France, asking them to respect Belgian neutrality; France pledged to do so, but Germany did not reply. Once the German ultimatum to Russia expired on the morning of 1 August, the two countries were at war. Later the same day, Wilhelm was informed by his ambassador in London, Prince Lichnowsky , that Britain would remain neutral if France was not attacked, and might not intervene at all given the ongoing Home Rule Crisis in Ireland. Jubilant at this news, he ordered General Moltke , the German chief of staff, to "march the whole of the ... army to the East". This allegedly brought Moltke to the verge of a nervous breakdown, before Lichnowsky realized he was mistaken. Once Wilhelm received a telegram from George V , it confirmed there had been a misunderstanding, and he told Moltke, "Now do what you want." Aware of German plans to attack through Belgium, French Commander-in-Chief Joseph Joffre asked his government for permission to cross the border and pre-empt such a move. To avoid violating Belgian neutrality, he was told any advance could come only after a German invasion. Instead, the French cabinet ordered its Army to withdraw 10 km behind the German frontier, to avoid any incident which might provoke the war. On 2 August, Germany occupied Luxembourg and exchanged fire with French units when German patrols entered French territory; on 3 August, they declared war on France and demanded free passage across Belgium, which was refused. Early on the morning of 4 August, the Germans invaded, and Albert I of Belgium called for assistance under the Treaty of London . Britain sent Germany an ultimatum demanding they withdraw from Belgium; when this expired at midnight, without a response, the two empires were at war. In the summer of 1914, the sovereigns of Europe were woven together by treaties, alliances, as well as secret agreements. The Triple Alliance (1882) encompassed the German Empire, Austria , and Italy. On 28 June 1914, Archduke Franz Ferdinand of Austria , heir presumptive to Emperor Franz Joseph I of Austria , visited Sarajevo , the capital of the recently annexed Bosnia and Herzegovina . Cvjetko Popović , Gavrilo Princip , Nedeljko Čabrinović , Trifko Grabež , and Vaso Čubrilović ( Bosnian Serbs ) and Muhamed Mehmedbašić (from the Bosniaks community), from the movement known as Young Bosnia , took up positions along the route taken by the Archduke's motorcade, to assassinate him. Supplied with arms by extremists within the Serbian Black Hand intelligence organisation, they hoped his death would free Bosnia from Austrian rule, although there was little agreement on what would replace it. Nedeljko Čabrinović threw a grenade at the Archduke's car and injured two of his aides, who were taken to hospital while the convoy carried on. The other assassins were also unsuccessful but, an hour later, as Ferdinand was returning from visiting the injured officers, his car took a wrong turn into a street where Gavrilo Princip was standing. He fired two pistol shots, fatally wounding Ferdinand and his wife Sophie . Although Emperor Franz Joseph was shocked by the incident, political and personal differences meant the two men were not close; allegedly, his first reported comment was "A higher power has re-established the order which I, alas, could not preserve". According to historian Zbyněk Zeman , in Vienna "the event almost failed to make any impression whatsoever. On 28 and 29 June, the crowds listened to music and drank wine, as if nothing had happened." Nevertheless, the impact of the murder of the heir to the throne was significant, and has been described by historian Christopher Clark as a " 9/11 effect , a terrorist event charged with historic meaning, transforming the political chemistry in Vienna". Austro-Hungarian authorities encouraged subsequent anti-Serb riots in Sarajevo , in which Bosnian Croats and Bosniaks killed two Bosnian Serbs and damaged numerous Serb-owned buildings. Violent actions against ethnic Serbs were also organised outside Sarajevo, in other cities in Austro-Hungarian-controlled Bosnia and Herzegovina, Croatia and Slovenia. Austro-Hungarian authorities in Bosnia and Herzegovina imprisoned and extradited approximately 5,500 prominent Serbs, 700 to 2,200 of whom died in prison. A further 460 Serbs were sentenced to death. A predominantly Bosniak special militia known as the Schutzkorps was established, and carried out the persecution of Serbs. The assassination initiated the July Crisis , a month of diplomatic manoeuvring between Austria-Hungary, Germany, Russia, France and Britain. Believing that Serbian intelligence helped organise Franz Ferdinand's murder, Austrian officials wanted to use the opportunity to end their interference in Bosnia and saw war as the best way of achieving this. However, the Foreign Ministry had no solid proof of Serbian involvement and a dossier used to make its case contained multiple errors. On 23 July, Austria delivered an ultimatum to Serbia, listing ten demands made intentionally unacceptable to provide an excuse for starting hostilities. Serbia ordered general mobilization on 25 July, but accepted all the terms, except for those empowering Austrian representatives to suppress "subversive elements" inside Serbia, and take part in the investigation and trial of Serbians linked to the assassination. Claiming this amounted to rejection, Austria broke off diplomatic relations and ordered partial mobilisation the next day; on 28 July, they declared war on Serbia and began shelling Belgrade . Having initiated war preparations on 25 July, Russia now ordered general mobilization in support of Serbia on 30th. Anxious to ensure backing from the SPD political opposition by presenting Russia as the aggressor, German Chancellor Bethmann Hollweg delayed the commencement of war preparations until 31 July. That afternoon, the Russian government were handed a note requiring them to "cease all war measures against Germany and Austria-Hungary" within 12 hours. A further German demand for neutrality was refused by the French who ordered general mobilization but delayed declaring war. The German General Staff had long assumed they faced a war on two fronts; the Schlieffen Plan envisaged using 80% of the army to defeat France, then switch to Russia. Since this required them to move quickly, mobilization orders were issued that afternoon. At a meeting on 29 July, the British cabinet had narrowly decided its obligations to Belgium under the 1839 Treaty of London did not require it to oppose a German invasion with military force. However, this was largely driven by Prime Minister Asquith 's desire to maintain unity; he and his senior Cabinet ministers were already committed to supporting France, the Royal Navy had been mobilised, and public opinion was strongly in favour of intervention. On 31 July, Britain sent notes to Germany and France, asking them to respect Belgian neutrality; France pledged to do so, but Germany did not reply. Once the German ultimatum to Russia expired on the morning of 1 August, the two countries were at war. Later the same day, Wilhelm was informed by his ambassador in London, Prince Lichnowsky , that Britain would remain neutral if France was not attacked, and might not intervene at all given the ongoing Home Rule Crisis in Ireland. Jubilant at this news, he ordered General Moltke , the German chief of staff, to "march the whole of the ... army to the East". This allegedly brought Moltke to the verge of a nervous breakdown, before Lichnowsky realized he was mistaken. Once Wilhelm received a telegram from George V , it confirmed there had been a misunderstanding, and he told Moltke, "Now do what you want." Aware of German plans to attack through Belgium, French Commander-in-Chief Joseph Joffre asked his government for permission to cross the border and pre-empt such a move. To avoid violating Belgian neutrality, he was told any advance could come only after a German invasion. Instead, the French cabinet ordered its Army to withdraw 10 km behind the German frontier, to avoid any incident which might provoke the war. On 2 August, Germany occupied Luxembourg and exchanged fire with French units when German patrols entered French territory; on 3 August, they declared war on France and demanded free passage across Belgium, which was refused. Early on the morning of 4 August, the Germans invaded, and Albert I of Belgium called for assistance under the Treaty of London . Britain sent Germany an ultimatum demanding they withdraw from Belgium; when this expired at midnight, without a response, the two empires were at war. The strategy of the Central Powers suffered from miscommunication. Germany promised to support Austria-Hungary's invasion of Serbia, but interpretations of what this meant differed. Previously tested deployment plans had been replaced early in 1914, but those had never been tested in exercises. Austro-Hungarian leaders believed Germany would cover its northern flank against Russia. Beginning on 12 August, the Austrians and Serbs clashed at the battles of the Cer and Kolubara ; over the next two weeks, Austrian attacks were repulsed with heavy losses, dashing their hopes of a swift victory and marking the first major Allied victories of the war. As a result, Austria had to keep sizeable forces on the Serbian front, weakening their efforts against Russia. Serbia's victory against Austria-Hungary in the 1914 invasion has been called one of the major upset victories of the twentieth century. In spring 1915, the campaign saw the first use of anti-aircraft warfare after an Austrian plane was shot down with ground-to-air fire, as well as the first medical evacuation by the Serbian army in autumn 1915. Upon mobilisation, 80% of the German Army was located on the Western Front, with the remainder acting as a screening force in the East; officially titled Aufmarsch II West, it is better known as the Schlieffen Plan after its creator, Alfred von Schlieffen , head of the German General Staff from 1891 to 1906. Rather than a direct attack across their shared frontier, the German right wing would sweep through the Netherlands and Belgium , then swing south, encircling Paris and trapping the French army against the Swiss border. Schlieffen estimated that this would take six weeks, after which the German army would transfer to the East and defeat the Russians. The plan was substantially modified by his successor, Helmuth von Moltke the Younger . Under Schlieffen, 85% of German forces in the west were assigned to the right wing, with the remainder holding along the frontier. By keeping his left-wing deliberately weak, he hoped to lure the French into an offensive into the "lost provinces" of Alsace-Lorraine , which was the strategy envisaged by their Plan XVII . However, Moltke grew concerned that the French might push too hard on his left flank and as the German Army increased in size from 1908 to 1914, he changed the allocation of forces between the two wings from 85:15 to 70:30. He also considered Dutch neutrality essential for German trade and cancelled the incursion into the Netherlands, which meant any delays in Belgium threatened the viability of the plan. Historian Richard Holmes argues that these changes meant the right wing was not strong enough to achieve decisive success and thus led to unrealistic goals and timings. The initial German advance in the West was very successful and by the end of August, the Allied left, which included the British Expeditionary Force (BEF), was in full retreat . At the same time, the French offensive in Alsace-Lorraine was a disastrous failure, with casualties exceeding 260,000, including 27,000 killed on 22 August during the Battle of the Frontiers . German planning provided broad strategic instructions while allowing army commanders considerable freedom in carrying them out at the front; this worked well in 1866 and 1870 but in 1914, von Kluck used this freedom to disobey orders, opening a gap between the German armies as they closed on Paris. The French army, reinforced by the British expeditionary corps, seized this opportunity to counter-attack and pushed the German army 40 to 80 km back. Both armies were then so exhausted that no decisive move could be implemented, so they settled in trenches, with the vain hope of breaking through as soon as they could build local superiority. In 1911, the Russian Stavka agreed with the French to attack Germany within fifteen days of mobilisation, ten days before the Germans had anticipated, although it meant the two Russian armies that entered East Prussia on 17 August did so without many of their support elements. By the end of 1914, German troops held strong defensive positions inside France, controlled the bulk of France's domestic coalfields, and inflicted 230,000 more casualties than it lost itself. However, communications problems, combined with questionable command decisions, cost Germany the chance of a decisive outcome, while it had failed to achieve the primary objective of avoiding a long, two-front war. As was apparent to several German leaders, this amounted to a strategic defeat; shortly after the Marne, Crown Prince Wilhelm told an American reporter "We have lost the war. It will go on for a long time but lost it is already." On 30 August 1914, New Zealand occupied German Samoa , now the independent state of Samoa . On 11 September, the Australian Naval and Military Expeditionary Force landed on the island of New Britain , then part of German New Guinea . On 28 October, the German cruiser SMS Emden sank the Russian cruiser Zhemchug in the Battle of Penang . Japan declared war on Germany before seizing territories in the Pacific, which later became the South Seas Mandate , as well as German Treaty ports on the Chinese Shandong peninsula at Tsingtao . After Vienna refused to withdraw its cruiser SMS Kaiserin Elisabeth from Tsingtao, Japan declared war on Austria-Hungary as well, and the ship was sunk at Tsingtao in November 1914. Within a few months, Allied forces had seized all German territories in the Pacific, leaving only isolated commerce raiders and a few holdouts in New Guinea. Some of the first clashes of the war involved British, French, and German colonial forces in Africa. On 6–7 August, French and British troops invaded the German protectorate of Togoland and Kamerun . On 10 August, German forces in South-West Africa attacked South Africa; sporadic and fierce fighting continued for the rest of the war. The German colonial forces in German East Africa , led by Colonel Paul von Lettow-Vorbeck , fought a guerrilla warfare campaign during World War I and only surrendered two weeks after the armistice took effect in Europe. Before the war, Germany had attempted to use Indian nationalism and pan-Islamism to its advantage, a policy continued post-1914 by instigating uprisings in India , while the Niedermayer–Hentig Expedition urged Afghanistan to join the war on the side of Central Powers. However, contrary to British fears of a revolt in India, the outbreak of the war saw a reduction in nationalist activity. This was largely because leaders from the Indian National Congress and other groups believed support for the British war effort would hasten Indian Home Rule , a promise allegedly made explicit in 1917 by Edwin Montagu , the Secretary of State for India . In 1914, the British Indian Army was larger than the British Army itself, and between 1914 and 1918 an estimated 1.3 million Indian soldiers and labourers served in Europe, Africa, and the Middle East, while the Government of India and their princely allies supplied large quantities of food, money, and ammunition. In all, 140,000 soldiers served on the Western Front and nearly 700,000 in the Middle East, with 47,746 killed and 65,126 wounded. The suffering engendered by the war, as well as the failure of the British government to grant self-government to India after the end of hostilities, bred disillusionment, resulting in the campaign for full independence led by Mahatma Gandhi . Pre-war military tactics that had emphasised open warfare and the individual rifleman proved obsolete when confronted with conditions prevailing in 1914. Technological advances allowed the creation of strong defensive systems largely impervious to massed infantry advances, such as barbed wire , machine guns and above all far more powerful artillery , which dominated the battlefield and made crossing open ground extremely difficult. Both sides struggled to develop tactics for breaching entrenched positions without suffering heavy casualties. In time, however, technology enabled the production of new offensive weapons, such as gas warfare and the tank . After the First Battle of the Marne in September 1914, Allied and German forces unsuccessfully tried to outflank each other, a series of manoeuvres later known as the " Race to the Sea ". By the end of 1914, the opposing forces confronted each other along an uninterrupted line of entrenched positions from the Channel to the Swiss border. Since the Germans were normally able to choose where to stand, they generally held the high ground, while their trenches tended to be better built; those constructed by the French and English were initially considered "temporary", only needed until an offensive would destroy the German defences. Both sides tried to break the stalemate using scientific and technological advances. On 22 April 1915, at the Second Battle of Ypres , the Germans (violating the Hague Convention ) used chlorine gas for the first time on the Western Front. Several types of gas soon became widely used by both sides and though it never proved a decisive, battle-winning weapon, it became one of the most feared and best-remembered horrors of the war. In February 1916, the Germans attacked French defensive positions at the Battle of Verdun , lasting until December 1916. The Germans made initial gains before French counter-attacks returned matters to near their starting point. Casualties were greater for the French, but the Germans bled heavily as well, with anywhere from 700,000 to 975,000 casualties suffered between the two combatants. Verdun became a symbol of French determination and self-sacrifice. The Battle of the Somme was an Anglo-French offensive from July to November 1916. The opening day on 1 July 1916 was the bloodiest single day in the history of the British Army , which suffered 57,500 casualties, including 19,200 dead. As a whole, the Somme offensive led to an estimated 420,000 British casualties, along with 200,000 French and 500,000 Germans. Gunfire was not the only cause of death; the diseases that emerged in the trenches were a major killer on both sides. The living conditions led to disease and infection, such as trench foot , lice , typhus , trench fever , and the ' Spanish flu '. At the start of the war, German cruisers were scattered across the globe, some of which were subsequently used to attack Allied merchant shipping . These were systematically hunted down by the Royal Navy, though not before causing considerable damage. One of the most successful was the SMS Emden , part of the German East Asia Squadron stationed at Qingdao, which seized or sank 15 merchantmen, as well as a Russian cruiser and a French destroyer. Most of the squadron was returning to Germany when it sank two British armoured cruisers at the Battle of Coronel in November 1914, before being virtually destroyed at the Battle of the Falkland Islands in December. The SMS Dresden escaped with a few auxiliaries, but after the Battle of Más a Tierra , these too were either destroyed or interned. Soon after the outbreak of hostilities, Britain began a naval blockade of Germany . This proved effective in cutting off vital military and civilian supplies, though it violated accepted international law. Britain also mined international waters which closed off entire sections of the ocean, even to neutral ships. Since there was limited response to this tactic of the British, Germany expected a similar response to its unrestricted submarine warfare. The Battle of Jutland [lower-alpha 12] in May/June 1916 was the only full-scale clash of battleships during the war, and one of the largest in history. The clash was indecisive, though the Germans inflicted more damage than they received, since thereafter the bulk of the German High Seas Fleet was confined to port. German U-boat attempted to cut the supply lines between North America and Britain. The nature of submarine warfare meant that attacks often came without warning, giving the crews of the merchant ships little hope of survival. The United States launched a protest, and Germany changed its rules of engagement. After the sinking of the passenger ship RMS Lusitania in 1915, Germany promised not to target passenger liners, while Britain armed its merchant ships, placing them beyond the protection of the " cruiser rules ", which demanded warning and movement of crews to "a place of safety" (a standard that lifeboats did not meet). Finally, in early 1917, Germany adopted a policy of unrestricted submarine warfare , realising the Americans would eventually enter the war. Germany sought to strangle Allied sea lanes before the United States could transport a large army overseas, but, after initial successes, eventually failed to do so. The U-boat threat lessened in 1917, when merchant ships began travelling in convoys , escorted by destroyers . This tactic made it difficult for U-boats to find targets, which significantly lessened losses; after the hydrophone and depth charges were introduced, destroyers could potentially successfully attack a submerged submarine. Convoys slowed the flow of supplies since ships had to wait as convoys were assembled; the solution was an extensive program of building new freighters. Troopships were too fast for the submarines and did not travel the North Atlantic in convoys. The U-boats sunk more than 5,000 Allied ships, at the cost of 199 submarines. World War I also saw the first use of aircraft carriers in combat, with HMS Furious launching Sopwith Camels in a successful raid against the Zeppelin hangars at Tondern in July 1918, as well as blimps for antisubmarine patrol. Faced with Russia in the east, Austria-Hungary could spare only one-third of its army to attack Serbia. After suffering heavy losses, the Austrians briefly occupied the Serbian capital, Belgrade . A Serbian counter-attack in the Battle of Kolubara succeeded in driving them from the country by the end of 1914. For the first 10 months of 1915, Austria-Hungary used most of its military reserves to fight Italy. German and Austro-Hungarian diplomats, however, scored a coup by persuading Bulgaria to join the attack on Serbia. The Austro-Hungarian provinces of Slovenia , Croatia and Bosnia provided troops for Austria-Hungary in the fight with Serbia, Russia and Italy. Montenegro allied itself with Serbia. Bulgaria declared war on Serbia on 14 October 1915 and joined in the attack by the Austro-Hungarian army under Mackensen's army of 250,000 that was already underway. Serbia was conquered in a little more than a month, as the Central Powers, now including Bulgaria, sent in 600,000 troops in total. The Serbian army, fighting on two fronts and facing certain defeat, retreated into northern Albania . The Serbs suffered defeat in the Battle of Kosovo . Montenegro covered the Serbian retreat toward the Adriatic coast in the Battle of Mojkovac on 6–7 January 1916, but ultimately the Austrians also conquered Montenegro. The surviving Serbian soldiers were then evacuated to Greece. After the conquest, Serbia was divided between Austro-Hungary and Bulgaria. In late 1915, a Franco-British force landed at Salonica in Greece to offer assistance and to pressure its government to declare war against the Central Powers. However, the pro-German King Constantine I dismissed the pro-Allied government of Eleftherios Venizelos before the Allied expeditionary force arrived. The Macedonian front was at first mostly static. French and Serbian forces retook limited areas of Macedonia by recapturing Bitola on 19 November 1916 following the costly Monastir offensive , which brought stabilisation of the front. Serbian and French troops finally made a breakthrough in September 1918 in the Vardar offensive , after most German and Austro-Hungarian troops had been withdrawn. The Bulgarians were defeated at the Battle of Dobro Pole , and by 25 September British and French troops had crossed the border into Bulgaria proper as the Bulgarian army collapsed. Bulgaria capitulated four days later, on 29 September 1918. The German high command responded by despatching troops to hold the line, but these forces were too weak to re-establish a front. The disappearance of the Macedonian front meant that the road to Budapest and Vienna was now opened to Allied forces. Hindenburg and Ludendorff concluded that the strategic and operational balance had now shifted decidedly against the Central Powers and, a day after the Bulgarian collapse, insisted on an immediate peace settlement. The Ottomans threatened Russia's Caucasian territories and Britain's communications with India via the Suez Canal . As the conflict progressed, the Ottoman Empire took advantage of the European powers' preoccupation with the war and conducted large-scale ethnic cleansing of the indigenous Armenian , Greek , and Assyrian Christian populations, known as the Armenian genocide , Greek genocide , and Sayfo respectively. The British and French opened overseas fronts with the Gallipoli (1915) and Mesopotamian campaigns (1914). In Gallipoli, the Ottoman Empire successfully repelled the British, French, and Australian and New Zealand Army Corps (ANZACs). In Mesopotamia , by contrast, after the defeat of the British defenders in the siege of Kut by the Ottomans (1915–16), British Imperial forces reorganised and captured Baghdad in March 1917. The British were aided in Mesopotamia by local Arab and Assyrian fighters, while the Ottomans employed local Kurdish and Turcoman tribes. Further to the west, the Suez Canal was defended from Ottoman attacks in 1915 and 1916; in August, a German and Ottoman force was defeated at the Battle of Romani by the ANZAC Mounted Division and the 52nd (Lowland) Infantry Division . Following this victory, an Egyptian Expeditionary Force advanced across the Sinai Peninsula , pushing Ottoman forces back in the Battle of Magdhaba in December and the Battle of Rafa on the border between the Egyptian Sinai and Ottoman Palestine in January 1917. Russian armies generally had success in the Caucasus campaign . Enver Pasha , supreme commander of the Ottoman armed forces, was ambitious and dreamed of re-conquering central Asia and areas that had been previously lost to Russia. He was, however, a poor commander. He launched an offensive against the Russians in the Caucasus in December 1914 with 100,000 troops, insisting on a frontal attack against mountainous Russian positions in winter. He lost 86% of his force at the Battle of Sarikamish . The Ottoman Empire, with German support, invaded Persia (modern Iran ) in December 1914 to cut off British and Russian access to petroleum reservoirs around Baku near the Caspian Sea . Persia, ostensibly neutral, had long been under the spheres of British and Russian influence. The Ottomans and Germans were aided by Kurdish and Azeri forces, together with a large number of major Iranian tribes, such as the Qashqai , Tangistanis , Lurs , and Khamseh , while the Russians and British had the support of Armenian and Assyrian forces. The Persian campaign was to last until 1918 and end in failure for the Ottomans and their allies. However, the Russian withdrawal from the war in 1917 led Armenian and Assyrian forces, who had hitherto inflicted a series of defeats upon the forces of the Ottomans and their allies, to be cut off from supply lines, outnumbered, outgunned and isolated, forcing them to fight and flee towards British lines in northern Mesopotamia. General Yudenich , the Russian commander from 1915 to 1916, drove the Turks out of most of the southern Caucasus with a string of victories. The Arab Revolt , instigated by the Arab bureau of the British Foreign Office , started in June 1916 with the Battle of Mecca , led by Sharif Hussein of Mecca . The Sharif declared the independence of the Kingdom of Hejaz and, with British assistance, conquered much of Ottoman-held Arabia, resulting finally in the Ottoman surrender of Damascus. Fakhri Pasha , the Ottoman commander of Medina , resisted for more than 2 + 1 ⁄ 2 years during the siege of Medina before surrendering in January 1919. The Senussi tribe, along the border of Italian Libya and British Egypt , incited and armed by the Turks, waged a small-scale guerrilla war against Allied troops. The British were forced to dispatch 12,000 troops to oppose them in the Senussi campaign . Their rebellion was finally crushed in mid-1916. Total Allied casualties on the Ottoman fronts amounted to 650,000 men. Total Ottoman casualties were 725,000, with 325,000 dead and 400,000 wounded. Though Italy joined the Triple Alliance in 1882, a treaty with its traditional Austrian enemy was so controversial that subsequent governments denied its existence and the terms were only made public in 1915. This arose from nationalist designs on Austro-Hungarian territory in Trentino , the Austrian Littoral , Rijeka and Dalmatia , which were considered vital to secure the borders established in 1866 . In 1902, Rome secretly had agreed with France to remain neutral if the latter was attacked by Germany, effectively nullifying its role in the Triple Alliance. When the war began in 1914, Italy argued the Triple Alliance was defensive and it was not obliged to support an Austrian attack on Serbia. Opposition to joining the Central Powers increased when Turkey became a member in September, since in 1911 Italy had occupied Ottoman possessions in Libya and the Dodecanese islands. To secure Italian neutrality, the Central Powers offered them Tunisia , while in return for an immediate entry into the war, the Allies agreed to their demands for Austrian territory and sovereignty over the Dodecanese. Although they remained secret, these provisions were incorporated into the April 1915 Treaty of London ; Italy joined the Triple Entente and, on 23 May, declared war on Austria-Hungary, followed by Germany fifteen months later. The pre-1914 Italian army was short of officers, trained men, adequate transport and modern weapons; by April 1915, some of these deficiencies had been remedied but it was still unprepared for the major offensive required by the Treaty of London. The advantage of superior numbers was offset by the difficult terrain; much of the fighting took place high in the Alps and Dolomites , where trench lines had to be cut through rock and ice and keeping troops supplied was a major challenge. These issues were exacerbated by unimaginative strategies and tactics. Between 1915 and 1917, the Italian commander, Luigi Cadorna , undertook a series of frontal assaults along the Isonzo , which made little progress and cost many lives; by the end of the war, Italian combat deaths totalled around 548,000. In the spring of 1916, the Austro-Hungarians counterattacked in Asiago in the Strafexpedition , but made little progress and were pushed by the Italians back to Tyrol. Although an Italian corps occupied southern Albania in May 1916, their main focus was the Isonzo front which, after the capture of Gorizia in August 1916, remained static until October 1917. After a combined Austro-German force won a major victory at Caporetto , Cadorna was replaced by Armando Diaz who retreated more than 100 kilometres (62 mi) before holding positions along the Piave River . A second Austrian offensive was repulsed in June 1918 and by October it was clear the Central Powers had lost the war. On 24 October, Diaz launched the Battle of Vittorio Veneto and initially met stubborn resistance, but with Austria-Hungary collapsing, Hungarian divisions in Italy demanded they be sent home. When this was granted, many others followed and the Imperial army disintegrated, the Italians taking over 300,000 prisoners. On 3 November, the Armistice of Villa Giusti ended hostilities between Austria-Hungary and Italy which occupied Trieste and areas along the Adriatic Sea awarded to it in 1915. As previously agreed with France, Russian plans at the start of the war were to simultaneously advance into Austrian Galicia and East Prussia as soon as possible. Although their attack on Galicia was largely successful, and the invasions achieved their aim of forcing Germany to divert troops from the Western Front, the speed of mobilisation meant they did so without much of their heavy equipment and support functions. These weaknesses contributed to Russian defeats at Tannenberg and the Masurian Lakes in August and September 1914, forcing them to withdraw from East Prussia with heavy losses. By spring 1915, they had also retreated from Galicia, and May 1915 Gorlice–Tarnów offensive than allowed the Central Powers to invade Russian-occupied Poland . Despite the successful June 1916 Brusilov offensive against the Austrians in eastern Galicia, shortages of supplies, heavy losses and command failures prevented the Russians from fully exploiting their victory. However, it was one of the most significant and impactful offensives of the war, diverting German resources from Verdun , relieving Austro-Hungarian pressure on the Italians, and convincing Romania to enter the war on the side of the Allies on 27 August. It also fatally weakened both the Austrian and Russian armies, whose offensive capabilities were badly affected by their losses and increased the disillusionment with the war that ultimately led to the Russian revolutions. Meanwhile, unrest grew in Russia as the Tsar remained at the front, with the home front controlled by Empress Alexandra . Her increasingly incompetent rule and food shortages in urban areas led to widespread protests and the murder of her favourite, Grigori Rasputin , at the end of 1916. Despite secretly agreeing to support the Triple Alliance in 1883, Romania increasingly found itself at odds with the Central Powers over their support for Bulgaria in the Balkan Wars and the status of ethnic Romanian communities in Hungarian -controlled Transylvania , which comprised an estimated 2.8 million of the 5.0 million population. With the ruling elite split into pro-German and pro-Entente factions, Romania remained neutral in 1914, arguing like Italy that because Austria-Hungary had declared war on Serbia, it was under no obligation to join them. They maintained this position for the next two years while allowing Germany and Austria to transport military supplies and advisors across Romanian territory. In September 1914, Russia acknowledged Romanian rights to Austro-Hungarian territories including Transylvania and Banat , whose acquisition had widespread popular support, and Russian success against Austria led Romania to join the Entente in the August 1916 Treaty of Bucharest. Under the strategic plan known as Hypothesis Z , the Romanian army planned an offensive into Transylvania, while defending Southern Dobruja and Giurgiu against a possible Bulgarian counterattack. On 27 August 1916, they attacked Transylvania and occupied substantial parts of the province before being driven back by the recently formed German 9th Army , led by former Chief of Staff Falkenhayn. A combined German-Bulgarian-Turkish offensive captured Dobruja and Giurgiu, although the bulk of the Romanian army managed to escape encirclement and retreated to Bucharest , which surrendered to the Central Powers on 6 December 1916. In the summer of 1917, a Central Powers offensive began in Romania under the command of August von Mackensen to knock Romania out of the war. Resulting in the battles of Oituz , Mărăști and Mărășești where up to 1,000,000 Central Powers troops were present. The battles lasted from 22 July to 3 September and eventually, the Romanian army was victorious advancing 500 km 2 . August von Mackensen could not plan for another offensive as he had to transfer troops to the Italian Front. Following the Russian revolution, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers, which recognised Romanian sovereignty over Bessarabia in return for ceding control of passes in the Carpathian Mountains to Austria-Hungary and leasing its oil wells to Germany for 99 years. Although approved by Parliament , King Ferdinand I refused to sign it, hoping for an Allied victory in the west. Romania re-entered the war on 10 November 1918 on the side of the Allies and the Treaty of Bucharest was formally annulled by the Armistice of 11 November 1918. [lower-alpha 13] On 12 December 1916, after ten brutal months of the Battle of Verdun and a successful offensive against Romania , Germany attempted to negotiate a peace with the Allies. However, this attempt was rejected out of hand as a "duplicitous war ruse". US president Woodrow Wilson attempted to intervene as a peacemaker, asking for both sides to state their demands and start negotiations. Lloyd George's War Cabinet considered the German offer to be a ploy to create divisions among the Allies. After initial outrage and much deliberation, they took Wilson's note as a separate effort, signalling that the United States was on the verge of entering the war against Germany following the "submarine outrages". While the Allies debated a response to Wilson's offer, the Germans chose to rebuff it in favour of "a direct exchange of views". Learning of the German response, the Allied governments were free to make clear demands in their response of 14 January. They sought restoration of damages, the evacuation of occupied territories, reparations for France, Russia and Romania, and a recognition of the principle of nationalities. This included the liberation of Italians, Slavs, Romanians, Czecho-Slovaks, and the creation of a "free and united Poland". The Allies sought guarantees that would prevent or limit future wars, complete with sanctions, as a condition of any peace settlement. The negotiations failed and the Entente powers rejected the German offer on the grounds of honour, and noted Germany had not put forward any specific proposals. By the end of 1916, Russian casualties totalled nearly five million killed, wounded or captured, with major urban areas affected by food shortages and high prices. In March 1917, Tsar Nicholas ordered the military to forcibly suppress a wave of strikes in Petrograd but the troops refused to fire on the crowds. Revolutionaries set up the Petrograd Soviet and fearing a left-wing takeover, the State Duma forced Nicholas to abdicate and established the Russian Provisional Government , which confirmed Russia's willingness to continue the war. However, the Petrograd Soviet refused to disband, creating competing power centres and causing confusion and chaos, with frontline soldiers becoming increasingly demoralised and unwilling to fight on. Following the Tsar's abdication, Vladimir Lenin —with the help of the German government—was ushered from Switzerland into Russia on 16 April 1917. Discontent and the weaknesses of the Provisional Government led to a rise in the popularity of the Bolshevik Party, led by Lenin, which demanded an immediate end to the war. The Revolution of November was followed in December by an armistice and negotiations with Germany. At first, the Bolsheviks refused the German terms, but when German troops began marching across Ukraine unopposed, the new government acceded to the Treaty of Brest-Litovsk on 3 March 1918. The treaty ceded vast territories, including Finland, Estonia, Latvia, Lithuania, and parts of Poland and Ukraine to the Central Powers. With the Russian Empire out of the war, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers in May 1918, ending the state of war between Romania and the Central Powers . Under the terms of the treaty, Romania had to give territory to Austria-Hungary and Bulgaria and lease its oil reserves to Germany. However, the terms also included the Central Powers' recognition of the union of Bessarabia with Romania. The United States was a major supplier of war material to the Allies but remained neutral in 1914, in large part due to domestic opposition. The most significant factor in creating the support Wilson needed was the German submarine offensive, which not only cost American lives but paralysed trade as ships were reluctant to put to sea. On 6 April 1917, Congress declared war on Germany as an "Associated Power" of the Allies. The United States Navy sent a battleship group to Scapa Flow to join the Grand Fleet, and provided convoy escorts. In April 1917, the United States Army had fewer than 300,000 men, including National Guard units, compared to British and French armies of 4.1 and 8.3 million respectively. The Selective Service Act of 1917 drafted 2.8 million men, though training and equipping such numbers was a huge logistical challenge. By June 1918, over 667,000 members of the American Expeditionary Forces (AEF) were transported to France, a figure which reached 2 million by the end of November. Despite his conviction that Germany must be defeated, Wilson went to war to ensure the US played a leading role in shaping the peace, which meant preserving the AEF as a separate military force, rather than being absorbed into British or French units as his Allies wanted. He was strongly supported by AEF commander General John J. Pershing , a proponent of pre-1914 "open warfare" who considered the French and British emphasis on artillery as misguided and incompatible with American "offensive spirit". Much to the frustration of his Allies, who had suffered heavy losses in 1917, he insisted on retaining control of American troops, and refused to commit them to the front line until able to operate as independent units. As a result, the first significant US involvement was the Meuse–Argonne offensive in late September 1918. In December 1916, Robert Nivelle replaced Pétain as commander of French armies on the Western Front and began planning a spring attack in Champagne , part of a joint Franco-British operation. Nivelle claimed the capture of his main objective, the Chemin des Dames , would achieve a massive breakthrough and cost no more than 15,000 casualties. Poor security meant German intelligence was well informed on tactics and timetables, but despite this, when the attack began on 16 April the French made substantial gains, before being brought to a halt by the newly built and extremely strong defences of the Hindenburg Line. Nivelle persisted with frontal assaults and, by 25 April, the French had suffered nearly 135,000 casualties, including 30,000 dead, most incurred in the first two days. Concurrent British attacks at Arras were more successful, though ultimately of little strategic value. Operating as a separate unit for the first time, the Canadian Corps capture of Vimy Ridge is viewed by many Canadians as a defining moment in creating a sense of national identity. Though Nivelle continued the offensive, on 3 May the 21st Division , which had been involved in some of the heaviest fighting at Verdun, refused orders to go into battle, initiating the French Army mutinies ; within days, "collective indiscipline" had spread to 54 divisions, while over 20,000 deserted. Unrest was almost entirely confined to the infantry, whose demands were largely non-political, including better economic support for families at home, and regular periods of leave, which Nivelle had ended. In March and April 1917, at the First and Second Battles of Gaza , German and Ottoman forces stopped the advance of the Egyptian Expeditionary Force, which had begun in August 1916 at the Battle of Romani. At the end of October, the Sinai and Palestine campaign resumed, when General Edmund Allenby 's XXth Corps , XXI Corps and Desert Mounted Corps won the Battle of Beersheba . Two Ottoman armies were defeated a few weeks later at the Battle of Mughar Ridge and, early in December, Jerusalem had been captured following another Ottoman defeat at the Battle of Jerusalem . About this time, Friedrich Freiherr Kress von Kressenstein was relieved of his duties as the Eighth Army's commander, replaced by Djevad Pasha , and a few months later the commander of the Ottoman Army in Palestine, Erich von Falkenhayn , was replaced by Otto Liman von Sanders . In early 1918, the front line was extended and the Jordan Valley was occupied, following the First Transjordan and the Second Transjordan attacks by British Empire forces in March and April 1918. In December 1917, the Central Powers signed an armistice with Russia, thus freeing large numbers of German troops for use in the West. With German reinforcements and new American troops pouring in, the outcome was to be decided on the Western Front. The Central Powers knew that they could not win a protracted war, but they held high hopes for success in a final quick offensive. Ludendorff drew up plans ( codenamed Operation Michael ) for the 1918 offensive on the Western Front. The operation commenced on 21 March 1918, with an attack on British forces near Saint-Quentin . German forces achieved an unprecedented advance of 60 kilometres (37 mi) . The initial offensive was a success; after heavy fighting, however, the offensive was halted. Lacking tanks or motorised artillery , the Germans were unable to consolidate their gains. The problems of re-supply were also exacerbated by increasing distances that now stretched over terrain that was shell-torn and often impassable to traffic. Following this, Germany launched Operation Georgette against the northern English Channel ports. The Allies halted the drive after limited territorial gains by Germany. The German Army to the south then conducted Operations Blücher and Yorck , pushing broadly towards Paris. Germany launched Operation Marne ( Second Battle of the Marne ) on 15 July, in an attempt to encircle Reims . The resulting counter-attack, which started the Hundred Days Offensive on 8 August, led to a marked collapse in German morale. By September, the Germans had fallen back to the Hindenburg Line. The Allies had advanced to the Hindenburg Line in the north and centre. German forces launched numerous counterattacks, but positions and outposts of the Line continued falling, with the BEF alone taking 30,441 prisoners in the last week of September. On 24 September, the Supreme Army Command informed the leaders in Berlin that armistice talks were inevitable. The final assault on the Hindenburg Line began with the Meuse-Argonne offensive , launched by American and French troops on 26 September. Two days later the Allied armies (Belgian, French and British) attacked around Ypres , and the day after the British Fourth and French First Army at St Quentin in the centre of the line. The following week, cooperating American and French units broke through in Champagne at the Battle of Blanc Mont Ridge (3–27 October), forcing the Germans off the commanding heights, and closing towards the Belgian frontier. On 8 October, the Hindenburg Line was pierced by British and Dominion troops of the First and Third British Armies at the Second Battle of Cambrai . Allied forces started the Vardar offensive on 15 September at two key points: Dobro Pole and near Dojran Lake . In the Battle of Dobro Pole , the Serbian and French armies had success after a three-day-long battle with relatively small casualties, and subsequently made a breakthrough in the front, something which was rarely seen in World War I. After the front was broken, Allied forces started to liberate Serbia and reached Skopje at 29 September, after which Bulgaria signed an armistice with the Allies on 30 September. The collapse of the Central Powers came swiftly. Bulgaria was the first to sign an armistice, the Armistice of Salonica on 29 September 1918. German Emperor Wilhelm II in a telegram to Bulgarian Tsar Ferdinand I described the situation thus: "Disgraceful! 62,000 Serbs decided the war!". On the same day, the German Supreme Army Command informed Kaiser Wilhelm II and the Imperial Chancellor Count Georg von Hertling , that the military situation facing Germany was hopeless. On 24 October, the Italians began a push that rapidly recovered territory lost after the Battle of Caporetto. This culminated in the Battle of Vittorio Veneto, marking the end of the Austro-Hungarian Army as an effective fighting force. The offensive also triggered the disintegration of the Austro-Hungarian Empire. During the last week of October, declarations of independence were made in Budapest, Prague, and Zagreb. On 29 October, the imperial authorities asked Italy for an armistice, but the Italians continued advancing, reaching Trento, Udine, and Trieste. On 3 November, Austria-Hungary sent a flag of truce to ask for an armistice ( Armistice of Villa Giusti ). The terms, arranged with the Allied Authorities in Paris, were communicated to the Austrian commander and accepted. The Armistice with Austria was signed in the Villa Giusti, near Padua , on 3 November. Austria and Hungary signed separate armistices following the overthrow of the Habsburg monarchy . In the following days, the Italian Army occupied Innsbruck and all Tyrol , with over 20,000 soldiers. On 30 October, the Ottoman Empire capitulated, and signed the Armistice of Mudros. With the military faltering and with widespread loss of confidence in the Kaiser leading to his abdication and fleeing of the country, Germany moved towards surrender. Prince Maximilian of Baden took charge of a new government on October 3 as Chancellor of Germany to negotiate with the Allies. Negotiations with President Wilson began immediately, in the hope that he would offer better terms than the British and French. Wilson demanded a constitutional monarchy and parliamentary control over the German military. In northern Germany, the German Revolution of 1918–1919 began at the end of October 1918. Units of the German Navy refused to set sail for a last, large-scale operation in a war they believed to be as good as lost, initiating the uprising. The sailors' revolt , which then ensued in the naval ports of Wilhelmshaven and Kiel , spread across the whole country within days and led to the proclamation of a republic on 9 November 1918, shortly thereafter to the abdication of Kaiser Wilhelm II , and German surrender. The strategy of the Central Powers suffered from miscommunication. Germany promised to support Austria-Hungary's invasion of Serbia, but interpretations of what this meant differed. Previously tested deployment plans had been replaced early in 1914, but those had never been tested in exercises. Austro-Hungarian leaders believed Germany would cover its northern flank against Russia. Beginning on 12 August, the Austrians and Serbs clashed at the battles of the Cer and Kolubara ; over the next two weeks, Austrian attacks were repulsed with heavy losses, dashing their hopes of a swift victory and marking the first major Allied victories of the war. As a result, Austria had to keep sizeable forces on the Serbian front, weakening their efforts against Russia. Serbia's victory against Austria-Hungary in the 1914 invasion has been called one of the major upset victories of the twentieth century. In spring 1915, the campaign saw the first use of anti-aircraft warfare after an Austrian plane was shot down with ground-to-air fire, as well as the first medical evacuation by the Serbian army in autumn 1915. Upon mobilisation, 80% of the German Army was located on the Western Front, with the remainder acting as a screening force in the East; officially titled Aufmarsch II West, it is better known as the Schlieffen Plan after its creator, Alfred von Schlieffen , head of the German General Staff from 1891 to 1906. Rather than a direct attack across their shared frontier, the German right wing would sweep through the Netherlands and Belgium , then swing south, encircling Paris and trapping the French army against the Swiss border. Schlieffen estimated that this would take six weeks, after which the German army would transfer to the East and defeat the Russians. The plan was substantially modified by his successor, Helmuth von Moltke the Younger . Under Schlieffen, 85% of German forces in the west were assigned to the right wing, with the remainder holding along the frontier. By keeping his left-wing deliberately weak, he hoped to lure the French into an offensive into the "lost provinces" of Alsace-Lorraine , which was the strategy envisaged by their Plan XVII . However, Moltke grew concerned that the French might push too hard on his left flank and as the German Army increased in size from 1908 to 1914, he changed the allocation of forces between the two wings from 85:15 to 70:30. He also considered Dutch neutrality essential for German trade and cancelled the incursion into the Netherlands, which meant any delays in Belgium threatened the viability of the plan. Historian Richard Holmes argues that these changes meant the right wing was not strong enough to achieve decisive success and thus led to unrealistic goals and timings. The initial German advance in the West was very successful and by the end of August, the Allied left, which included the British Expeditionary Force (BEF), was in full retreat . At the same time, the French offensive in Alsace-Lorraine was a disastrous failure, with casualties exceeding 260,000, including 27,000 killed on 22 August during the Battle of the Frontiers . German planning provided broad strategic instructions while allowing army commanders considerable freedom in carrying them out at the front; this worked well in 1866 and 1870 but in 1914, von Kluck used this freedom to disobey orders, opening a gap between the German armies as they closed on Paris. The French army, reinforced by the British expeditionary corps, seized this opportunity to counter-attack and pushed the German army 40 to 80 km back. Both armies were then so exhausted that no decisive move could be implemented, so they settled in trenches, with the vain hope of breaking through as soon as they could build local superiority. In 1911, the Russian Stavka agreed with the French to attack Germany within fifteen days of mobilisation, ten days before the Germans had anticipated, although it meant the two Russian armies that entered East Prussia on 17 August did so without many of their support elements. By the end of 1914, German troops held strong defensive positions inside France, controlled the bulk of France's domestic coalfields, and inflicted 230,000 more casualties than it lost itself. However, communications problems, combined with questionable command decisions, cost Germany the chance of a decisive outcome, while it had failed to achieve the primary objective of avoiding a long, two-front war. As was apparent to several German leaders, this amounted to a strategic defeat; shortly after the Marne, Crown Prince Wilhelm told an American reporter "We have lost the war. It will go on for a long time but lost it is already." On 30 August 1914, New Zealand occupied German Samoa , now the independent state of Samoa . On 11 September, the Australian Naval and Military Expeditionary Force landed on the island of New Britain , then part of German New Guinea . On 28 October, the German cruiser SMS Emden sank the Russian cruiser Zhemchug in the Battle of Penang . Japan declared war on Germany before seizing territories in the Pacific, which later became the South Seas Mandate , as well as German Treaty ports on the Chinese Shandong peninsula at Tsingtao . After Vienna refused to withdraw its cruiser SMS Kaiserin Elisabeth from Tsingtao, Japan declared war on Austria-Hungary as well, and the ship was sunk at Tsingtao in November 1914. Within a few months, Allied forces had seized all German territories in the Pacific, leaving only isolated commerce raiders and a few holdouts in New Guinea. Some of the first clashes of the war involved British, French, and German colonial forces in Africa. On 6–7 August, French and British troops invaded the German protectorate of Togoland and Kamerun . On 10 August, German forces in South-West Africa attacked South Africa; sporadic and fierce fighting continued for the rest of the war. The German colonial forces in German East Africa , led by Colonel Paul von Lettow-Vorbeck , fought a guerrilla warfare campaign during World War I and only surrendered two weeks after the armistice took effect in Europe. Before the war, Germany had attempted to use Indian nationalism and pan-Islamism to its advantage, a policy continued post-1914 by instigating uprisings in India , while the Niedermayer–Hentig Expedition urged Afghanistan to join the war on the side of Central Powers. However, contrary to British fears of a revolt in India, the outbreak of the war saw a reduction in nationalist activity. This was largely because leaders from the Indian National Congress and other groups believed support for the British war effort would hasten Indian Home Rule , a promise allegedly made explicit in 1917 by Edwin Montagu , the Secretary of State for India . In 1914, the British Indian Army was larger than the British Army itself, and between 1914 and 1918 an estimated 1.3 million Indian soldiers and labourers served in Europe, Africa, and the Middle East, while the Government of India and their princely allies supplied large quantities of food, money, and ammunition. In all, 140,000 soldiers served on the Western Front and nearly 700,000 in the Middle East, with 47,746 killed and 65,126 wounded. The suffering engendered by the war, as well as the failure of the British government to grant self-government to India after the end of hostilities, bred disillusionment, resulting in the campaign for full independence led by Mahatma Gandhi . The strategy of the Central Powers suffered from miscommunication. Germany promised to support Austria-Hungary's invasion of Serbia, but interpretations of what this meant differed. Previously tested deployment plans had been replaced early in 1914, but those had never been tested in exercises. Austro-Hungarian leaders believed Germany would cover its northern flank against Russia. Beginning on 12 August, the Austrians and Serbs clashed at the battles of the Cer and Kolubara ; over the next two weeks, Austrian attacks were repulsed with heavy losses, dashing their hopes of a swift victory and marking the first major Allied victories of the war. As a result, Austria had to keep sizeable forces on the Serbian front, weakening their efforts against Russia. Serbia's victory against Austria-Hungary in the 1914 invasion has been called one of the major upset victories of the twentieth century. In spring 1915, the campaign saw the first use of anti-aircraft warfare after an Austrian plane was shot down with ground-to-air fire, as well as the first medical evacuation by the Serbian army in autumn 1915. Upon mobilisation, 80% of the German Army was located on the Western Front, with the remainder acting as a screening force in the East; officially titled Aufmarsch II West, it is better known as the Schlieffen Plan after its creator, Alfred von Schlieffen , head of the German General Staff from 1891 to 1906. Rather than a direct attack across their shared frontier, the German right wing would sweep through the Netherlands and Belgium , then swing south, encircling Paris and trapping the French army against the Swiss border. Schlieffen estimated that this would take six weeks, after which the German army would transfer to the East and defeat the Russians. The plan was substantially modified by his successor, Helmuth von Moltke the Younger . Under Schlieffen, 85% of German forces in the west were assigned to the right wing, with the remainder holding along the frontier. By keeping his left-wing deliberately weak, he hoped to lure the French into an offensive into the "lost provinces" of Alsace-Lorraine , which was the strategy envisaged by their Plan XVII . However, Moltke grew concerned that the French might push too hard on his left flank and as the German Army increased in size from 1908 to 1914, he changed the allocation of forces between the two wings from 85:15 to 70:30. He also considered Dutch neutrality essential for German trade and cancelled the incursion into the Netherlands, which meant any delays in Belgium threatened the viability of the plan. Historian Richard Holmes argues that these changes meant the right wing was not strong enough to achieve decisive success and thus led to unrealistic goals and timings. The initial German advance in the West was very successful and by the end of August, the Allied left, which included the British Expeditionary Force (BEF), was in full retreat . At the same time, the French offensive in Alsace-Lorraine was a disastrous failure, with casualties exceeding 260,000, including 27,000 killed on 22 August during the Battle of the Frontiers . German planning provided broad strategic instructions while allowing army commanders considerable freedom in carrying them out at the front; this worked well in 1866 and 1870 but in 1914, von Kluck used this freedom to disobey orders, opening a gap between the German armies as they closed on Paris. The French army, reinforced by the British expeditionary corps, seized this opportunity to counter-attack and pushed the German army 40 to 80 km back. Both armies were then so exhausted that no decisive move could be implemented, so they settled in trenches, with the vain hope of breaking through as soon as they could build local superiority. In 1911, the Russian Stavka agreed with the French to attack Germany within fifteen days of mobilisation, ten days before the Germans had anticipated, although it meant the two Russian armies that entered East Prussia on 17 August did so without many of their support elements. By the end of 1914, German troops held strong defensive positions inside France, controlled the bulk of France's domestic coalfields, and inflicted 230,000 more casualties than it lost itself. However, communications problems, combined with questionable command decisions, cost Germany the chance of a decisive outcome, while it had failed to achieve the primary objective of avoiding a long, two-front war. As was apparent to several German leaders, this amounted to a strategic defeat; shortly after the Marne, Crown Prince Wilhelm told an American reporter "We have lost the war. It will go on for a long time but lost it is already." On 30 August 1914, New Zealand occupied German Samoa , now the independent state of Samoa . On 11 September, the Australian Naval and Military Expeditionary Force landed on the island of New Britain , then part of German New Guinea . On 28 October, the German cruiser SMS Emden sank the Russian cruiser Zhemchug in the Battle of Penang . Japan declared war on Germany before seizing territories in the Pacific, which later became the South Seas Mandate , as well as German Treaty ports on the Chinese Shandong peninsula at Tsingtao . After Vienna refused to withdraw its cruiser SMS Kaiserin Elisabeth from Tsingtao, Japan declared war on Austria-Hungary as well, and the ship was sunk at Tsingtao in November 1914. Within a few months, Allied forces had seized all German territories in the Pacific, leaving only isolated commerce raiders and a few holdouts in New Guinea. Some of the first clashes of the war involved British, French, and German colonial forces in Africa. On 6–7 August, French and British troops invaded the German protectorate of Togoland and Kamerun . On 10 August, German forces in South-West Africa attacked South Africa; sporadic and fierce fighting continued for the rest of the war. The German colonial forces in German East Africa , led by Colonel Paul von Lettow-Vorbeck , fought a guerrilla warfare campaign during World War I and only surrendered two weeks after the armistice took effect in Europe. Before the war, Germany had attempted to use Indian nationalism and pan-Islamism to its advantage, a policy continued post-1914 by instigating uprisings in India , while the Niedermayer–Hentig Expedition urged Afghanistan to join the war on the side of Central Powers. However, contrary to British fears of a revolt in India, the outbreak of the war saw a reduction in nationalist activity. This was largely because leaders from the Indian National Congress and other groups believed support for the British war effort would hasten Indian Home Rule , a promise allegedly made explicit in 1917 by Edwin Montagu , the Secretary of State for India . In 1914, the British Indian Army was larger than the British Army itself, and between 1914 and 1918 an estimated 1.3 million Indian soldiers and labourers served in Europe, Africa, and the Middle East, while the Government of India and their princely allies supplied large quantities of food, money, and ammunition. In all, 140,000 soldiers served on the Western Front and nearly 700,000 in the Middle East, with 47,746 killed and 65,126 wounded. The suffering engendered by the war, as well as the failure of the British government to grant self-government to India after the end of hostilities, bred disillusionment, resulting in the campaign for full independence led by Mahatma Gandhi . Pre-war military tactics that had emphasised open warfare and the individual rifleman proved obsolete when confronted with conditions prevailing in 1914. Technological advances allowed the creation of strong defensive systems largely impervious to massed infantry advances, such as barbed wire , machine guns and above all far more powerful artillery , which dominated the battlefield and made crossing open ground extremely difficult. Both sides struggled to develop tactics for breaching entrenched positions without suffering heavy casualties. In time, however, technology enabled the production of new offensive weapons, such as gas warfare and the tank . After the First Battle of the Marne in September 1914, Allied and German forces unsuccessfully tried to outflank each other, a series of manoeuvres later known as the " Race to the Sea ". By the end of 1914, the opposing forces confronted each other along an uninterrupted line of entrenched positions from the Channel to the Swiss border. Since the Germans were normally able to choose where to stand, they generally held the high ground, while their trenches tended to be better built; those constructed by the French and English were initially considered "temporary", only needed until an offensive would destroy the German defences. Both sides tried to break the stalemate using scientific and technological advances. On 22 April 1915, at the Second Battle of Ypres , the Germans (violating the Hague Convention ) used chlorine gas for the first time on the Western Front. Several types of gas soon became widely used by both sides and though it never proved a decisive, battle-winning weapon, it became one of the most feared and best-remembered horrors of the war. In February 1916, the Germans attacked French defensive positions at the Battle of Verdun , lasting until December 1916. The Germans made initial gains before French counter-attacks returned matters to near their starting point. Casualties were greater for the French, but the Germans bled heavily as well, with anywhere from 700,000 to 975,000 casualties suffered between the two combatants. Verdun became a symbol of French determination and self-sacrifice. The Battle of the Somme was an Anglo-French offensive from July to November 1916. The opening day on 1 July 1916 was the bloodiest single day in the history of the British Army , which suffered 57,500 casualties, including 19,200 dead. As a whole, the Somme offensive led to an estimated 420,000 British casualties, along with 200,000 French and 500,000 Germans. Gunfire was not the only cause of death; the diseases that emerged in the trenches were a major killer on both sides. The living conditions led to disease and infection, such as trench foot , lice , typhus , trench fever , and the ' Spanish flu '. Pre-war military tactics that had emphasised open warfare and the individual rifleman proved obsolete when confronted with conditions prevailing in 1914. Technological advances allowed the creation of strong defensive systems largely impervious to massed infantry advances, such as barbed wire , machine guns and above all far more powerful artillery , which dominated the battlefield and made crossing open ground extremely difficult. Both sides struggled to develop tactics for breaching entrenched positions without suffering heavy casualties. In time, however, technology enabled the production of new offensive weapons, such as gas warfare and the tank . After the First Battle of the Marne in September 1914, Allied and German forces unsuccessfully tried to outflank each other, a series of manoeuvres later known as the " Race to the Sea ". By the end of 1914, the opposing forces confronted each other along an uninterrupted line of entrenched positions from the Channel to the Swiss border. Since the Germans were normally able to choose where to stand, they generally held the high ground, while their trenches tended to be better built; those constructed by the French and English were initially considered "temporary", only needed until an offensive would destroy the German defences. Both sides tried to break the stalemate using scientific and technological advances. On 22 April 1915, at the Second Battle of Ypres , the Germans (violating the Hague Convention ) used chlorine gas for the first time on the Western Front. Several types of gas soon became widely used by both sides and though it never proved a decisive, battle-winning weapon, it became one of the most feared and best-remembered horrors of the war. In February 1916, the Germans attacked French defensive positions at the Battle of Verdun , lasting until December 1916. The Germans made initial gains before French counter-attacks returned matters to near their starting point. Casualties were greater for the French, but the Germans bled heavily as well, with anywhere from 700,000 to 975,000 casualties suffered between the two combatants. Verdun became a symbol of French determination and self-sacrifice. The Battle of the Somme was an Anglo-French offensive from July to November 1916. The opening day on 1 July 1916 was the bloodiest single day in the history of the British Army , which suffered 57,500 casualties, including 19,200 dead. As a whole, the Somme offensive led to an estimated 420,000 British casualties, along with 200,000 French and 500,000 Germans. Gunfire was not the only cause of death; the diseases that emerged in the trenches were a major killer on both sides. The living conditions led to disease and infection, such as trench foot , lice , typhus , trench fever , and the ' Spanish flu '. At the start of the war, German cruisers were scattered across the globe, some of which were subsequently used to attack Allied merchant shipping . These were systematically hunted down by the Royal Navy, though not before causing considerable damage. One of the most successful was the SMS Emden , part of the German East Asia Squadron stationed at Qingdao, which seized or sank 15 merchantmen, as well as a Russian cruiser and a French destroyer. Most of the squadron was returning to Germany when it sank two British armoured cruisers at the Battle of Coronel in November 1914, before being virtually destroyed at the Battle of the Falkland Islands in December. The SMS Dresden escaped with a few auxiliaries, but after the Battle of Más a Tierra , these too were either destroyed or interned. Soon after the outbreak of hostilities, Britain began a naval blockade of Germany . This proved effective in cutting off vital military and civilian supplies, though it violated accepted international law. Britain also mined international waters which closed off entire sections of the ocean, even to neutral ships. Since there was limited response to this tactic of the British, Germany expected a similar response to its unrestricted submarine warfare. The Battle of Jutland [lower-alpha 12] in May/June 1916 was the only full-scale clash of battleships during the war, and one of the largest in history. The clash was indecisive, though the Germans inflicted more damage than they received, since thereafter the bulk of the German High Seas Fleet was confined to port. German U-boat attempted to cut the supply lines between North America and Britain. The nature of submarine warfare meant that attacks often came without warning, giving the crews of the merchant ships little hope of survival. The United States launched a protest, and Germany changed its rules of engagement. After the sinking of the passenger ship RMS Lusitania in 1915, Germany promised not to target passenger liners, while Britain armed its merchant ships, placing them beyond the protection of the " cruiser rules ", which demanded warning and movement of crews to "a place of safety" (a standard that lifeboats did not meet). Finally, in early 1917, Germany adopted a policy of unrestricted submarine warfare , realising the Americans would eventually enter the war. Germany sought to strangle Allied sea lanes before the United States could transport a large army overseas, but, after initial successes, eventually failed to do so. The U-boat threat lessened in 1917, when merchant ships began travelling in convoys , escorted by destroyers . This tactic made it difficult for U-boats to find targets, which significantly lessened losses; after the hydrophone and depth charges were introduced, destroyers could potentially successfully attack a submerged submarine. Convoys slowed the flow of supplies since ships had to wait as convoys were assembled; the solution was an extensive program of building new freighters. Troopships were too fast for the submarines and did not travel the North Atlantic in convoys. The U-boats sunk more than 5,000 Allied ships, at the cost of 199 submarines. World War I also saw the first use of aircraft carriers in combat, with HMS Furious launching Sopwith Camels in a successful raid against the Zeppelin hangars at Tondern in July 1918, as well as blimps for antisubmarine patrol. Faced with Russia in the east, Austria-Hungary could spare only one-third of its army to attack Serbia. After suffering heavy losses, the Austrians briefly occupied the Serbian capital, Belgrade . A Serbian counter-attack in the Battle of Kolubara succeeded in driving them from the country by the end of 1914. For the first 10 months of 1915, Austria-Hungary used most of its military reserves to fight Italy. German and Austro-Hungarian diplomats, however, scored a coup by persuading Bulgaria to join the attack on Serbia. The Austro-Hungarian provinces of Slovenia , Croatia and Bosnia provided troops for Austria-Hungary in the fight with Serbia, Russia and Italy. Montenegro allied itself with Serbia. Bulgaria declared war on Serbia on 14 October 1915 and joined in the attack by the Austro-Hungarian army under Mackensen's army of 250,000 that was already underway. Serbia was conquered in a little more than a month, as the Central Powers, now including Bulgaria, sent in 600,000 troops in total. The Serbian army, fighting on two fronts and facing certain defeat, retreated into northern Albania . The Serbs suffered defeat in the Battle of Kosovo . Montenegro covered the Serbian retreat toward the Adriatic coast in the Battle of Mojkovac on 6–7 January 1916, but ultimately the Austrians also conquered Montenegro. The surviving Serbian soldiers were then evacuated to Greece. After the conquest, Serbia was divided between Austro-Hungary and Bulgaria. In late 1915, a Franco-British force landed at Salonica in Greece to offer assistance and to pressure its government to declare war against the Central Powers. However, the pro-German King Constantine I dismissed the pro-Allied government of Eleftherios Venizelos before the Allied expeditionary force arrived. The Macedonian front was at first mostly static. French and Serbian forces retook limited areas of Macedonia by recapturing Bitola on 19 November 1916 following the costly Monastir offensive , which brought stabilisation of the front. Serbian and French troops finally made a breakthrough in September 1918 in the Vardar offensive , after most German and Austro-Hungarian troops had been withdrawn. The Bulgarians were defeated at the Battle of Dobro Pole , and by 25 September British and French troops had crossed the border into Bulgaria proper as the Bulgarian army collapsed. Bulgaria capitulated four days later, on 29 September 1918. The German high command responded by despatching troops to hold the line, but these forces were too weak to re-establish a front. The disappearance of the Macedonian front meant that the road to Budapest and Vienna was now opened to Allied forces. Hindenburg and Ludendorff concluded that the strategic and operational balance had now shifted decidedly against the Central Powers and, a day after the Bulgarian collapse, insisted on an immediate peace settlement. The Ottomans threatened Russia's Caucasian territories and Britain's communications with India via the Suez Canal . As the conflict progressed, the Ottoman Empire took advantage of the European powers' preoccupation with the war and conducted large-scale ethnic cleansing of the indigenous Armenian , Greek , and Assyrian Christian populations, known as the Armenian genocide , Greek genocide , and Sayfo respectively. The British and French opened overseas fronts with the Gallipoli (1915) and Mesopotamian campaigns (1914). In Gallipoli, the Ottoman Empire successfully repelled the British, French, and Australian and New Zealand Army Corps (ANZACs). In Mesopotamia , by contrast, after the defeat of the British defenders in the siege of Kut by the Ottomans (1915–16), British Imperial forces reorganised and captured Baghdad in March 1917. The British were aided in Mesopotamia by local Arab and Assyrian fighters, while the Ottomans employed local Kurdish and Turcoman tribes. Further to the west, the Suez Canal was defended from Ottoman attacks in 1915 and 1916; in August, a German and Ottoman force was defeated at the Battle of Romani by the ANZAC Mounted Division and the 52nd (Lowland) Infantry Division . Following this victory, an Egyptian Expeditionary Force advanced across the Sinai Peninsula , pushing Ottoman forces back in the Battle of Magdhaba in December and the Battle of Rafa on the border between the Egyptian Sinai and Ottoman Palestine in January 1917. Russian armies generally had success in the Caucasus campaign . Enver Pasha , supreme commander of the Ottoman armed forces, was ambitious and dreamed of re-conquering central Asia and areas that had been previously lost to Russia. He was, however, a poor commander. He launched an offensive against the Russians in the Caucasus in December 1914 with 100,000 troops, insisting on a frontal attack against mountainous Russian positions in winter. He lost 86% of his force at the Battle of Sarikamish . The Ottoman Empire, with German support, invaded Persia (modern Iran ) in December 1914 to cut off British and Russian access to petroleum reservoirs around Baku near the Caspian Sea . Persia, ostensibly neutral, had long been under the spheres of British and Russian influence. The Ottomans and Germans were aided by Kurdish and Azeri forces, together with a large number of major Iranian tribes, such as the Qashqai , Tangistanis , Lurs , and Khamseh , while the Russians and British had the support of Armenian and Assyrian forces. The Persian campaign was to last until 1918 and end in failure for the Ottomans and their allies. However, the Russian withdrawal from the war in 1917 led Armenian and Assyrian forces, who had hitherto inflicted a series of defeats upon the forces of the Ottomans and their allies, to be cut off from supply lines, outnumbered, outgunned and isolated, forcing them to fight and flee towards British lines in northern Mesopotamia. General Yudenich , the Russian commander from 1915 to 1916, drove the Turks out of most of the southern Caucasus with a string of victories. The Arab Revolt , instigated by the Arab bureau of the British Foreign Office , started in June 1916 with the Battle of Mecca , led by Sharif Hussein of Mecca . The Sharif declared the independence of the Kingdom of Hejaz and, with British assistance, conquered much of Ottoman-held Arabia, resulting finally in the Ottoman surrender of Damascus. Fakhri Pasha , the Ottoman commander of Medina , resisted for more than 2 + 1 ⁄ 2 years during the siege of Medina before surrendering in January 1919. The Senussi tribe, along the border of Italian Libya and British Egypt , incited and armed by the Turks, waged a small-scale guerrilla war against Allied troops. The British were forced to dispatch 12,000 troops to oppose them in the Senussi campaign . Their rebellion was finally crushed in mid-1916. Total Allied casualties on the Ottoman fronts amounted to 650,000 men. Total Ottoman casualties were 725,000, with 325,000 dead and 400,000 wounded. Though Italy joined the Triple Alliance in 1882, a treaty with its traditional Austrian enemy was so controversial that subsequent governments denied its existence and the terms were only made public in 1915. This arose from nationalist designs on Austro-Hungarian territory in Trentino , the Austrian Littoral , Rijeka and Dalmatia , which were considered vital to secure the borders established in 1866 . In 1902, Rome secretly had agreed with France to remain neutral if the latter was attacked by Germany, effectively nullifying its role in the Triple Alliance. When the war began in 1914, Italy argued the Triple Alliance was defensive and it was not obliged to support an Austrian attack on Serbia. Opposition to joining the Central Powers increased when Turkey became a member in September, since in 1911 Italy had occupied Ottoman possessions in Libya and the Dodecanese islands. To secure Italian neutrality, the Central Powers offered them Tunisia , while in return for an immediate entry into the war, the Allies agreed to their demands for Austrian territory and sovereignty over the Dodecanese. Although they remained secret, these provisions were incorporated into the April 1915 Treaty of London ; Italy joined the Triple Entente and, on 23 May, declared war on Austria-Hungary, followed by Germany fifteen months later. The pre-1914 Italian army was short of officers, trained men, adequate transport and modern weapons; by April 1915, some of these deficiencies had been remedied but it was still unprepared for the major offensive required by the Treaty of London. The advantage of superior numbers was offset by the difficult terrain; much of the fighting took place high in the Alps and Dolomites , where trench lines had to be cut through rock and ice and keeping troops supplied was a major challenge. These issues were exacerbated by unimaginative strategies and tactics. Between 1915 and 1917, the Italian commander, Luigi Cadorna , undertook a series of frontal assaults along the Isonzo , which made little progress and cost many lives; by the end of the war, Italian combat deaths totalled around 548,000. In the spring of 1916, the Austro-Hungarians counterattacked in Asiago in the Strafexpedition , but made little progress and were pushed by the Italians back to Tyrol. Although an Italian corps occupied southern Albania in May 1916, their main focus was the Isonzo front which, after the capture of Gorizia in August 1916, remained static until October 1917. After a combined Austro-German force won a major victory at Caporetto , Cadorna was replaced by Armando Diaz who retreated more than 100 kilometres (62 mi) before holding positions along the Piave River . A second Austrian offensive was repulsed in June 1918 and by October it was clear the Central Powers had lost the war. On 24 October, Diaz launched the Battle of Vittorio Veneto and initially met stubborn resistance, but with Austria-Hungary collapsing, Hungarian divisions in Italy demanded they be sent home. When this was granted, many others followed and the Imperial army disintegrated, the Italians taking over 300,000 prisoners. On 3 November, the Armistice of Villa Giusti ended hostilities between Austria-Hungary and Italy which occupied Trieste and areas along the Adriatic Sea awarded to it in 1915. Faced with Russia in the east, Austria-Hungary could spare only one-third of its army to attack Serbia. After suffering heavy losses, the Austrians briefly occupied the Serbian capital, Belgrade . A Serbian counter-attack in the Battle of Kolubara succeeded in driving them from the country by the end of 1914. For the first 10 months of 1915, Austria-Hungary used most of its military reserves to fight Italy. German and Austro-Hungarian diplomats, however, scored a coup by persuading Bulgaria to join the attack on Serbia. The Austro-Hungarian provinces of Slovenia , Croatia and Bosnia provided troops for Austria-Hungary in the fight with Serbia, Russia and Italy. Montenegro allied itself with Serbia. Bulgaria declared war on Serbia on 14 October 1915 and joined in the attack by the Austro-Hungarian army under Mackensen's army of 250,000 that was already underway. Serbia was conquered in a little more than a month, as the Central Powers, now including Bulgaria, sent in 600,000 troops in total. The Serbian army, fighting on two fronts and facing certain defeat, retreated into northern Albania . The Serbs suffered defeat in the Battle of Kosovo . Montenegro covered the Serbian retreat toward the Adriatic coast in the Battle of Mojkovac on 6–7 January 1916, but ultimately the Austrians also conquered Montenegro. The surviving Serbian soldiers were then evacuated to Greece. After the conquest, Serbia was divided between Austro-Hungary and Bulgaria. In late 1915, a Franco-British force landed at Salonica in Greece to offer assistance and to pressure its government to declare war against the Central Powers. However, the pro-German King Constantine I dismissed the pro-Allied government of Eleftherios Venizelos before the Allied expeditionary force arrived. The Macedonian front was at first mostly static. French and Serbian forces retook limited areas of Macedonia by recapturing Bitola on 19 November 1916 following the costly Monastir offensive , which brought stabilisation of the front. Serbian and French troops finally made a breakthrough in September 1918 in the Vardar offensive , after most German and Austro-Hungarian troops had been withdrawn. The Bulgarians were defeated at the Battle of Dobro Pole , and by 25 September British and French troops had crossed the border into Bulgaria proper as the Bulgarian army collapsed. Bulgaria capitulated four days later, on 29 September 1918. The German high command responded by despatching troops to hold the line, but these forces were too weak to re-establish a front. The disappearance of the Macedonian front meant that the road to Budapest and Vienna was now opened to Allied forces. Hindenburg and Ludendorff concluded that the strategic and operational balance had now shifted decidedly against the Central Powers and, a day after the Bulgarian collapse, insisted on an immediate peace settlement. The Ottomans threatened Russia's Caucasian territories and Britain's communications with India via the Suez Canal . As the conflict progressed, the Ottoman Empire took advantage of the European powers' preoccupation with the war and conducted large-scale ethnic cleansing of the indigenous Armenian , Greek , and Assyrian Christian populations, known as the Armenian genocide , Greek genocide , and Sayfo respectively. The British and French opened overseas fronts with the Gallipoli (1915) and Mesopotamian campaigns (1914). In Gallipoli, the Ottoman Empire successfully repelled the British, French, and Australian and New Zealand Army Corps (ANZACs). In Mesopotamia , by contrast, after the defeat of the British defenders in the siege of Kut by the Ottomans (1915–16), British Imperial forces reorganised and captured Baghdad in March 1917. The British were aided in Mesopotamia by local Arab and Assyrian fighters, while the Ottomans employed local Kurdish and Turcoman tribes. Further to the west, the Suez Canal was defended from Ottoman attacks in 1915 and 1916; in August, a German and Ottoman force was defeated at the Battle of Romani by the ANZAC Mounted Division and the 52nd (Lowland) Infantry Division . Following this victory, an Egyptian Expeditionary Force advanced across the Sinai Peninsula , pushing Ottoman forces back in the Battle of Magdhaba in December and the Battle of Rafa on the border between the Egyptian Sinai and Ottoman Palestine in January 1917. Russian armies generally had success in the Caucasus campaign . Enver Pasha , supreme commander of the Ottoman armed forces, was ambitious and dreamed of re-conquering central Asia and areas that had been previously lost to Russia. He was, however, a poor commander. He launched an offensive against the Russians in the Caucasus in December 1914 with 100,000 troops, insisting on a frontal attack against mountainous Russian positions in winter. He lost 86% of his force at the Battle of Sarikamish . The Ottoman Empire, with German support, invaded Persia (modern Iran ) in December 1914 to cut off British and Russian access to petroleum reservoirs around Baku near the Caspian Sea . Persia, ostensibly neutral, had long been under the spheres of British and Russian influence. The Ottomans and Germans were aided by Kurdish and Azeri forces, together with a large number of major Iranian tribes, such as the Qashqai , Tangistanis , Lurs , and Khamseh , while the Russians and British had the support of Armenian and Assyrian forces. The Persian campaign was to last until 1918 and end in failure for the Ottomans and their allies. However, the Russian withdrawal from the war in 1917 led Armenian and Assyrian forces, who had hitherto inflicted a series of defeats upon the forces of the Ottomans and their allies, to be cut off from supply lines, outnumbered, outgunned and isolated, forcing them to fight and flee towards British lines in northern Mesopotamia. General Yudenich , the Russian commander from 1915 to 1916, drove the Turks out of most of the southern Caucasus with a string of victories. The Arab Revolt , instigated by the Arab bureau of the British Foreign Office , started in June 1916 with the Battle of Mecca , led by Sharif Hussein of Mecca . The Sharif declared the independence of the Kingdom of Hejaz and, with British assistance, conquered much of Ottoman-held Arabia, resulting finally in the Ottoman surrender of Damascus. Fakhri Pasha , the Ottoman commander of Medina , resisted for more than 2 + 1 ⁄ 2 years during the siege of Medina before surrendering in January 1919. The Senussi tribe, along the border of Italian Libya and British Egypt , incited and armed by the Turks, waged a small-scale guerrilla war against Allied troops. The British were forced to dispatch 12,000 troops to oppose them in the Senussi campaign . Their rebellion was finally crushed in mid-1916. Total Allied casualties on the Ottoman fronts amounted to 650,000 men. Total Ottoman casualties were 725,000, with 325,000 dead and 400,000 wounded. Though Italy joined the Triple Alliance in 1882, a treaty with its traditional Austrian enemy was so controversial that subsequent governments denied its existence and the terms were only made public in 1915. This arose from nationalist designs on Austro-Hungarian territory in Trentino , the Austrian Littoral , Rijeka and Dalmatia , which were considered vital to secure the borders established in 1866 . In 1902, Rome secretly had agreed with France to remain neutral if the latter was attacked by Germany, effectively nullifying its role in the Triple Alliance. When the war began in 1914, Italy argued the Triple Alliance was defensive and it was not obliged to support an Austrian attack on Serbia. Opposition to joining the Central Powers increased when Turkey became a member in September, since in 1911 Italy had occupied Ottoman possessions in Libya and the Dodecanese islands. To secure Italian neutrality, the Central Powers offered them Tunisia , while in return for an immediate entry into the war, the Allies agreed to their demands for Austrian territory and sovereignty over the Dodecanese. Although they remained secret, these provisions were incorporated into the April 1915 Treaty of London ; Italy joined the Triple Entente and, on 23 May, declared war on Austria-Hungary, followed by Germany fifteen months later. The pre-1914 Italian army was short of officers, trained men, adequate transport and modern weapons; by April 1915, some of these deficiencies had been remedied but it was still unprepared for the major offensive required by the Treaty of London. The advantage of superior numbers was offset by the difficult terrain; much of the fighting took place high in the Alps and Dolomites , where trench lines had to be cut through rock and ice and keeping troops supplied was a major challenge. These issues were exacerbated by unimaginative strategies and tactics. Between 1915 and 1917, the Italian commander, Luigi Cadorna , undertook a series of frontal assaults along the Isonzo , which made little progress and cost many lives; by the end of the war, Italian combat deaths totalled around 548,000. In the spring of 1916, the Austro-Hungarians counterattacked in Asiago in the Strafexpedition , but made little progress and were pushed by the Italians back to Tyrol. Although an Italian corps occupied southern Albania in May 1916, their main focus was the Isonzo front which, after the capture of Gorizia in August 1916, remained static until October 1917. After a combined Austro-German force won a major victory at Caporetto , Cadorna was replaced by Armando Diaz who retreated more than 100 kilometres (62 mi) before holding positions along the Piave River . A second Austrian offensive was repulsed in June 1918 and by October it was clear the Central Powers had lost the war. On 24 October, Diaz launched the Battle of Vittorio Veneto and initially met stubborn resistance, but with Austria-Hungary collapsing, Hungarian divisions in Italy demanded they be sent home. When this was granted, many others followed and the Imperial army disintegrated, the Italians taking over 300,000 prisoners. On 3 November, the Armistice of Villa Giusti ended hostilities between Austria-Hungary and Italy which occupied Trieste and areas along the Adriatic Sea awarded to it in 1915. As previously agreed with France, Russian plans at the start of the war were to simultaneously advance into Austrian Galicia and East Prussia as soon as possible. Although their attack on Galicia was largely successful, and the invasions achieved their aim of forcing Germany to divert troops from the Western Front, the speed of mobilisation meant they did so without much of their heavy equipment and support functions. These weaknesses contributed to Russian defeats at Tannenberg and the Masurian Lakes in August and September 1914, forcing them to withdraw from East Prussia with heavy losses. By spring 1915, they had also retreated from Galicia, and May 1915 Gorlice–Tarnów offensive than allowed the Central Powers to invade Russian-occupied Poland . Despite the successful June 1916 Brusilov offensive against the Austrians in eastern Galicia, shortages of supplies, heavy losses and command failures prevented the Russians from fully exploiting their victory. However, it was one of the most significant and impactful offensives of the war, diverting German resources from Verdun , relieving Austro-Hungarian pressure on the Italians, and convincing Romania to enter the war on the side of the Allies on 27 August. It also fatally weakened both the Austrian and Russian armies, whose offensive capabilities were badly affected by their losses and increased the disillusionment with the war that ultimately led to the Russian revolutions. Meanwhile, unrest grew in Russia as the Tsar remained at the front, with the home front controlled by Empress Alexandra . Her increasingly incompetent rule and food shortages in urban areas led to widespread protests and the murder of her favourite, Grigori Rasputin , at the end of 1916. Despite secretly agreeing to support the Triple Alliance in 1883, Romania increasingly found itself at odds with the Central Powers over their support for Bulgaria in the Balkan Wars and the status of ethnic Romanian communities in Hungarian -controlled Transylvania , which comprised an estimated 2.8 million of the 5.0 million population. With the ruling elite split into pro-German and pro-Entente factions, Romania remained neutral in 1914, arguing like Italy that because Austria-Hungary had declared war on Serbia, it was under no obligation to join them. They maintained this position for the next two years while allowing Germany and Austria to transport military supplies and advisors across Romanian territory. In September 1914, Russia acknowledged Romanian rights to Austro-Hungarian territories including Transylvania and Banat , whose acquisition had widespread popular support, and Russian success against Austria led Romania to join the Entente in the August 1916 Treaty of Bucharest. Under the strategic plan known as Hypothesis Z , the Romanian army planned an offensive into Transylvania, while defending Southern Dobruja and Giurgiu against a possible Bulgarian counterattack. On 27 August 1916, they attacked Transylvania and occupied substantial parts of the province before being driven back by the recently formed German 9th Army , led by former Chief of Staff Falkenhayn. A combined German-Bulgarian-Turkish offensive captured Dobruja and Giurgiu, although the bulk of the Romanian army managed to escape encirclement and retreated to Bucharest , which surrendered to the Central Powers on 6 December 1916. In the summer of 1917, a Central Powers offensive began in Romania under the command of August von Mackensen to knock Romania out of the war. Resulting in the battles of Oituz , Mărăști and Mărășești where up to 1,000,000 Central Powers troops were present. The battles lasted from 22 July to 3 September and eventually, the Romanian army was victorious advancing 500 km 2 . August von Mackensen could not plan for another offensive as he had to transfer troops to the Italian Front. Following the Russian revolution, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers, which recognised Romanian sovereignty over Bessarabia in return for ceding control of passes in the Carpathian Mountains to Austria-Hungary and leasing its oil wells to Germany for 99 years. Although approved by Parliament , King Ferdinand I refused to sign it, hoping for an Allied victory in the west. Romania re-entered the war on 10 November 1918 on the side of the Allies and the Treaty of Bucharest was formally annulled by the Armistice of 11 November 1918. [lower-alpha 13]As previously agreed with France, Russian plans at the start of the war were to simultaneously advance into Austrian Galicia and East Prussia as soon as possible. Although their attack on Galicia was largely successful, and the invasions achieved their aim of forcing Germany to divert troops from the Western Front, the speed of mobilisation meant they did so without much of their heavy equipment and support functions. These weaknesses contributed to Russian defeats at Tannenberg and the Masurian Lakes in August and September 1914, forcing them to withdraw from East Prussia with heavy losses. By spring 1915, they had also retreated from Galicia, and May 1915 Gorlice–Tarnów offensive than allowed the Central Powers to invade Russian-occupied Poland . Despite the successful June 1916 Brusilov offensive against the Austrians in eastern Galicia, shortages of supplies, heavy losses and command failures prevented the Russians from fully exploiting their victory. However, it was one of the most significant and impactful offensives of the war, diverting German resources from Verdun , relieving Austro-Hungarian pressure on the Italians, and convincing Romania to enter the war on the side of the Allies on 27 August. It also fatally weakened both the Austrian and Russian armies, whose offensive capabilities were badly affected by their losses and increased the disillusionment with the war that ultimately led to the Russian revolutions. Meanwhile, unrest grew in Russia as the Tsar remained at the front, with the home front controlled by Empress Alexandra . Her increasingly incompetent rule and food shortages in urban areas led to widespread protests and the murder of her favourite, Grigori Rasputin , at the end of 1916. Despite secretly agreeing to support the Triple Alliance in 1883, Romania increasingly found itself at odds with the Central Powers over their support for Bulgaria in the Balkan Wars and the status of ethnic Romanian communities in Hungarian -controlled Transylvania , which comprised an estimated 2.8 million of the 5.0 million population. With the ruling elite split into pro-German and pro-Entente factions, Romania remained neutral in 1914, arguing like Italy that because Austria-Hungary had declared war on Serbia, it was under no obligation to join them. They maintained this position for the next two years while allowing Germany and Austria to transport military supplies and advisors across Romanian territory. In September 1914, Russia acknowledged Romanian rights to Austro-Hungarian territories including Transylvania and Banat , whose acquisition had widespread popular support, and Russian success against Austria led Romania to join the Entente in the August 1916 Treaty of Bucharest. Under the strategic plan known as Hypothesis Z , the Romanian army planned an offensive into Transylvania, while defending Southern Dobruja and Giurgiu against a possible Bulgarian counterattack. On 27 August 1916, they attacked Transylvania and occupied substantial parts of the province before being driven back by the recently formed German 9th Army , led by former Chief of Staff Falkenhayn. A combined German-Bulgarian-Turkish offensive captured Dobruja and Giurgiu, although the bulk of the Romanian army managed to escape encirclement and retreated to Bucharest , which surrendered to the Central Powers on 6 December 1916. In the summer of 1917, a Central Powers offensive began in Romania under the command of August von Mackensen to knock Romania out of the war. Resulting in the battles of Oituz , Mărăști and Mărășești where up to 1,000,000 Central Powers troops were present. The battles lasted from 22 July to 3 September and eventually, the Romanian army was victorious advancing 500 km 2 . August von Mackensen could not plan for another offensive as he had to transfer troops to the Italian Front. Following the Russian revolution, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers, which recognised Romanian sovereignty over Bessarabia in return for ceding control of passes in the Carpathian Mountains to Austria-Hungary and leasing its oil wells to Germany for 99 years. Although approved by Parliament , King Ferdinand I refused to sign it, hoping for an Allied victory in the west. Romania re-entered the war on 10 November 1918 on the side of the Allies and the Treaty of Bucharest was formally annulled by the Armistice of 11 November 1918. [lower-alpha 13]On 12 December 1916, after ten brutal months of the Battle of Verdun and a successful offensive against Romania , Germany attempted to negotiate a peace with the Allies. However, this attempt was rejected out of hand as a "duplicitous war ruse". US president Woodrow Wilson attempted to intervene as a peacemaker, asking for both sides to state their demands and start negotiations. Lloyd George's War Cabinet considered the German offer to be a ploy to create divisions among the Allies. After initial outrage and much deliberation, they took Wilson's note as a separate effort, signalling that the United States was on the verge of entering the war against Germany following the "submarine outrages". While the Allies debated a response to Wilson's offer, the Germans chose to rebuff it in favour of "a direct exchange of views". Learning of the German response, the Allied governments were free to make clear demands in their response of 14 January. They sought restoration of damages, the evacuation of occupied territories, reparations for France, Russia and Romania, and a recognition of the principle of nationalities. This included the liberation of Italians, Slavs, Romanians, Czecho-Slovaks, and the creation of a "free and united Poland". The Allies sought guarantees that would prevent or limit future wars, complete with sanctions, as a condition of any peace settlement. The negotiations failed and the Entente powers rejected the German offer on the grounds of honour, and noted Germany had not put forward any specific proposals. By the end of 1916, Russian casualties totalled nearly five million killed, wounded or captured, with major urban areas affected by food shortages and high prices. In March 1917, Tsar Nicholas ordered the military to forcibly suppress a wave of strikes in Petrograd but the troops refused to fire on the crowds. Revolutionaries set up the Petrograd Soviet and fearing a left-wing takeover, the State Duma forced Nicholas to abdicate and established the Russian Provisional Government , which confirmed Russia's willingness to continue the war. However, the Petrograd Soviet refused to disband, creating competing power centres and causing confusion and chaos, with frontline soldiers becoming increasingly demoralised and unwilling to fight on. Following the Tsar's abdication, Vladimir Lenin —with the help of the German government—was ushered from Switzerland into Russia on 16 April 1917. Discontent and the weaknesses of the Provisional Government led to a rise in the popularity of the Bolshevik Party, led by Lenin, which demanded an immediate end to the war. The Revolution of November was followed in December by an armistice and negotiations with Germany. At first, the Bolsheviks refused the German terms, but when German troops began marching across Ukraine unopposed, the new government acceded to the Treaty of Brest-Litovsk on 3 March 1918. The treaty ceded vast territories, including Finland, Estonia, Latvia, Lithuania, and parts of Poland and Ukraine to the Central Powers. With the Russian Empire out of the war, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers in May 1918, ending the state of war between Romania and the Central Powers . Under the terms of the treaty, Romania had to give territory to Austria-Hungary and Bulgaria and lease its oil reserves to Germany. However, the terms also included the Central Powers' recognition of the union of Bessarabia with Romania. The United States was a major supplier of war material to the Allies but remained neutral in 1914, in large part due to domestic opposition. The most significant factor in creating the support Wilson needed was the German submarine offensive, which not only cost American lives but paralysed trade as ships were reluctant to put to sea. On 6 April 1917, Congress declared war on Germany as an "Associated Power" of the Allies. The United States Navy sent a battleship group to Scapa Flow to join the Grand Fleet, and provided convoy escorts. In April 1917, the United States Army had fewer than 300,000 men, including National Guard units, compared to British and French armies of 4.1 and 8.3 million respectively. The Selective Service Act of 1917 drafted 2.8 million men, though training and equipping such numbers was a huge logistical challenge. By June 1918, over 667,000 members of the American Expeditionary Forces (AEF) were transported to France, a figure which reached 2 million by the end of November. Despite his conviction that Germany must be defeated, Wilson went to war to ensure the US played a leading role in shaping the peace, which meant preserving the AEF as a separate military force, rather than being absorbed into British or French units as his Allies wanted. He was strongly supported by AEF commander General John J. Pershing , a proponent of pre-1914 "open warfare" who considered the French and British emphasis on artillery as misguided and incompatible with American "offensive spirit". Much to the frustration of his Allies, who had suffered heavy losses in 1917, he insisted on retaining control of American troops, and refused to commit them to the front line until able to operate as independent units. As a result, the first significant US involvement was the Meuse–Argonne offensive in late September 1918. In December 1916, Robert Nivelle replaced Pétain as commander of French armies on the Western Front and began planning a spring attack in Champagne , part of a joint Franco-British operation. Nivelle claimed the capture of his main objective, the Chemin des Dames , would achieve a massive breakthrough and cost no more than 15,000 casualties. Poor security meant German intelligence was well informed on tactics and timetables, but despite this, when the attack began on 16 April the French made substantial gains, before being brought to a halt by the newly built and extremely strong defences of the Hindenburg Line. Nivelle persisted with frontal assaults and, by 25 April, the French had suffered nearly 135,000 casualties, including 30,000 dead, most incurred in the first two days. Concurrent British attacks at Arras were more successful, though ultimately of little strategic value. Operating as a separate unit for the first time, the Canadian Corps capture of Vimy Ridge is viewed by many Canadians as a defining moment in creating a sense of national identity. Though Nivelle continued the offensive, on 3 May the 21st Division , which had been involved in some of the heaviest fighting at Verdun, refused orders to go into battle, initiating the French Army mutinies ; within days, "collective indiscipline" had spread to 54 divisions, while over 20,000 deserted. Unrest was almost entirely confined to the infantry, whose demands were largely non-political, including better economic support for families at home, and regular periods of leave, which Nivelle had ended. In March and April 1917, at the First and Second Battles of Gaza , German and Ottoman forces stopped the advance of the Egyptian Expeditionary Force, which had begun in August 1916 at the Battle of Romani. At the end of October, the Sinai and Palestine campaign resumed, when General Edmund Allenby 's XXth Corps , XXI Corps and Desert Mounted Corps won the Battle of Beersheba . Two Ottoman armies were defeated a few weeks later at the Battle of Mughar Ridge and, early in December, Jerusalem had been captured following another Ottoman defeat at the Battle of Jerusalem . About this time, Friedrich Freiherr Kress von Kressenstein was relieved of his duties as the Eighth Army's commander, replaced by Djevad Pasha , and a few months later the commander of the Ottoman Army in Palestine, Erich von Falkenhayn , was replaced by Otto Liman von Sanders . In early 1918, the front line was extended and the Jordan Valley was occupied, following the First Transjordan and the Second Transjordan attacks by British Empire forces in March and April 1918. In December 1917, the Central Powers signed an armistice with Russia, thus freeing large numbers of German troops for use in the West. With German reinforcements and new American troops pouring in, the outcome was to be decided on the Western Front. The Central Powers knew that they could not win a protracted war, but they held high hopes for success in a final quick offensive. Ludendorff drew up plans ( codenamed Operation Michael ) for the 1918 offensive on the Western Front. The operation commenced on 21 March 1918, with an attack on British forces near Saint-Quentin . German forces achieved an unprecedented advance of 60 kilometres (37 mi) . The initial offensive was a success; after heavy fighting, however, the offensive was halted. Lacking tanks or motorised artillery , the Germans were unable to consolidate their gains. The problems of re-supply were also exacerbated by increasing distances that now stretched over terrain that was shell-torn and often impassable to traffic. Following this, Germany launched Operation Georgette against the northern English Channel ports. The Allies halted the drive after limited territorial gains by Germany. The German Army to the south then conducted Operations Blücher and Yorck , pushing broadly towards Paris. Germany launched Operation Marne ( Second Battle of the Marne ) on 15 July, in an attempt to encircle Reims . The resulting counter-attack, which started the Hundred Days Offensive on 8 August, led to a marked collapse in German morale. By September, the Germans had fallen back to the Hindenburg Line. The Allies had advanced to the Hindenburg Line in the north and centre. German forces launched numerous counterattacks, but positions and outposts of the Line continued falling, with the BEF alone taking 30,441 prisoners in the last week of September. On 24 September, the Supreme Army Command informed the leaders in Berlin that armistice talks were inevitable. The final assault on the Hindenburg Line began with the Meuse-Argonne offensive , launched by American and French troops on 26 September. Two days later the Allied armies (Belgian, French and British) attacked around Ypres , and the day after the British Fourth and French First Army at St Quentin in the centre of the line. The following week, cooperating American and French units broke through in Champagne at the Battle of Blanc Mont Ridge (3–27 October), forcing the Germans off the commanding heights, and closing towards the Belgian frontier. On 8 October, the Hindenburg Line was pierced by British and Dominion troops of the First and Third British Armies at the Second Battle of Cambrai . Allied forces started the Vardar offensive on 15 September at two key points: Dobro Pole and near Dojran Lake . In the Battle of Dobro Pole , the Serbian and French armies had success after a three-day-long battle with relatively small casualties, and subsequently made a breakthrough in the front, something which was rarely seen in World War I. After the front was broken, Allied forces started to liberate Serbia and reached Skopje at 29 September, after which Bulgaria signed an armistice with the Allies on 30 September. By the end of 1916, Russian casualties totalled nearly five million killed, wounded or captured, with major urban areas affected by food shortages and high prices. In March 1917, Tsar Nicholas ordered the military to forcibly suppress a wave of strikes in Petrograd but the troops refused to fire on the crowds. Revolutionaries set up the Petrograd Soviet and fearing a left-wing takeover, the State Duma forced Nicholas to abdicate and established the Russian Provisional Government , which confirmed Russia's willingness to continue the war. However, the Petrograd Soviet refused to disband, creating competing power centres and causing confusion and chaos, with frontline soldiers becoming increasingly demoralised and unwilling to fight on. Following the Tsar's abdication, Vladimir Lenin —with the help of the German government—was ushered from Switzerland into Russia on 16 April 1917. Discontent and the weaknesses of the Provisional Government led to a rise in the popularity of the Bolshevik Party, led by Lenin, which demanded an immediate end to the war. The Revolution of November was followed in December by an armistice and negotiations with Germany. At first, the Bolsheviks refused the German terms, but when German troops began marching across Ukraine unopposed, the new government acceded to the Treaty of Brest-Litovsk on 3 March 1918. The treaty ceded vast territories, including Finland, Estonia, Latvia, Lithuania, and parts of Poland and Ukraine to the Central Powers. With the Russian Empire out of the war, Romania found itself alone on the Eastern Front and signed the Treaty of Bucharest with the Central Powers in May 1918, ending the state of war between Romania and the Central Powers . Under the terms of the treaty, Romania had to give territory to Austria-Hungary and Bulgaria and lease its oil reserves to Germany. However, the terms also included the Central Powers' recognition of the union of Bessarabia with Romania. The United States was a major supplier of war material to the Allies but remained neutral in 1914, in large part due to domestic opposition. The most significant factor in creating the support Wilson needed was the German submarine offensive, which not only cost American lives but paralysed trade as ships were reluctant to put to sea. On 6 April 1917, Congress declared war on Germany as an "Associated Power" of the Allies. The United States Navy sent a battleship group to Scapa Flow to join the Grand Fleet, and provided convoy escorts. In April 1917, the United States Army had fewer than 300,000 men, including National Guard units, compared to British and French armies of 4.1 and 8.3 million respectively. The Selective Service Act of 1917 drafted 2.8 million men, though training and equipping such numbers was a huge logistical challenge. By June 1918, over 667,000 members of the American Expeditionary Forces (AEF) were transported to France, a figure which reached 2 million by the end of November. Despite his conviction that Germany must be defeated, Wilson went to war to ensure the US played a leading role in shaping the peace, which meant preserving the AEF as a separate military force, rather than being absorbed into British or French units as his Allies wanted. He was strongly supported by AEF commander General John J. Pershing , a proponent of pre-1914 "open warfare" who considered the French and British emphasis on artillery as misguided and incompatible with American "offensive spirit". Much to the frustration of his Allies, who had suffered heavy losses in 1917, he insisted on retaining control of American troops, and refused to commit them to the front line until able to operate as independent units. As a result, the first significant US involvement was the Meuse–Argonne offensive in late September 1918. In December 1916, Robert Nivelle replaced Pétain as commander of French armies on the Western Front and began planning a spring attack in Champagne , part of a joint Franco-British operation. Nivelle claimed the capture of his main objective, the Chemin des Dames , would achieve a massive breakthrough and cost no more than 15,000 casualties. Poor security meant German intelligence was well informed on tactics and timetables, but despite this, when the attack began on 16 April the French made substantial gains, before being brought to a halt by the newly built and extremely strong defences of the Hindenburg Line. Nivelle persisted with frontal assaults and, by 25 April, the French had suffered nearly 135,000 casualties, including 30,000 dead, most incurred in the first two days. Concurrent British attacks at Arras were more successful, though ultimately of little strategic value. Operating as a separate unit for the first time, the Canadian Corps capture of Vimy Ridge is viewed by many Canadians as a defining moment in creating a sense of national identity. Though Nivelle continued the offensive, on 3 May the 21st Division , which had been involved in some of the heaviest fighting at Verdun, refused orders to go into battle, initiating the French Army mutinies ; within days, "collective indiscipline" had spread to 54 divisions, while over 20,000 deserted. Unrest was almost entirely confined to the infantry, whose demands were largely non-political, including better economic support for families at home, and regular periods of leave, which Nivelle had ended. In March and April 1917, at the First and Second Battles of Gaza , German and Ottoman forces stopped the advance of the Egyptian Expeditionary Force, which had begun in August 1916 at the Battle of Romani. At the end of October, the Sinai and Palestine campaign resumed, when General Edmund Allenby 's XXth Corps , XXI Corps and Desert Mounted Corps won the Battle of Beersheba . Two Ottoman armies were defeated a few weeks later at the Battle of Mughar Ridge and, early in December, Jerusalem had been captured following another Ottoman defeat at the Battle of Jerusalem . About this time, Friedrich Freiherr Kress von Kressenstein was relieved of his duties as the Eighth Army's commander, replaced by Djevad Pasha , and a few months later the commander of the Ottoman Army in Palestine, Erich von Falkenhayn , was replaced by Otto Liman von Sanders . In early 1918, the front line was extended and the Jordan Valley was occupied, following the First Transjordan and the Second Transjordan attacks by British Empire forces in March and April 1918. In December 1917, the Central Powers signed an armistice with Russia, thus freeing large numbers of German troops for use in the West. With German reinforcements and new American troops pouring in, the outcome was to be decided on the Western Front. The Central Powers knew that they could not win a protracted war, but they held high hopes for success in a final quick offensive. Ludendorff drew up plans ( codenamed Operation Michael ) for the 1918 offensive on the Western Front. The operation commenced on 21 March 1918, with an attack on British forces near Saint-Quentin . German forces achieved an unprecedented advance of 60 kilometres (37 mi) . The initial offensive was a success; after heavy fighting, however, the offensive was halted. Lacking tanks or motorised artillery , the Germans were unable to consolidate their gains. The problems of re-supply were also exacerbated by increasing distances that now stretched over terrain that was shell-torn and often impassable to traffic. Following this, Germany launched Operation Georgette against the northern English Channel ports. The Allies halted the drive after limited territorial gains by Germany. The German Army to the south then conducted Operations Blücher and Yorck , pushing broadly towards Paris. Germany launched Operation Marne ( Second Battle of the Marne ) on 15 July, in an attempt to encircle Reims . The resulting counter-attack, which started the Hundred Days Offensive on 8 August, led to a marked collapse in German morale. By September, the Germans had fallen back to the Hindenburg Line. The Allies had advanced to the Hindenburg Line in the north and centre. German forces launched numerous counterattacks, but positions and outposts of the Line continued falling, with the BEF alone taking 30,441 prisoners in the last week of September. On 24 September, the Supreme Army Command informed the leaders in Berlin that armistice talks were inevitable. The final assault on the Hindenburg Line began with the Meuse-Argonne offensive , launched by American and French troops on 26 September. Two days later the Allied armies (Belgian, French and British) attacked around Ypres , and the day after the British Fourth and French First Army at St Quentin in the centre of the line. The following week, cooperating American and French units broke through in Champagne at the Battle of Blanc Mont Ridge (3–27 October), forcing the Germans off the commanding heights, and closing towards the Belgian frontier. On 8 October, the Hindenburg Line was pierced by British and Dominion troops of the First and Third British Armies at the Second Battle of Cambrai . Allied forces started the Vardar offensive on 15 September at two key points: Dobro Pole and near Dojran Lake . In the Battle of Dobro Pole , the Serbian and French armies had success after a three-day-long battle with relatively small casualties, and subsequently made a breakthrough in the front, something which was rarely seen in World War I. After the front was broken, Allied forces started to liberate Serbia and reached Skopje at 29 September, after which Bulgaria signed an armistice with the Allies on 30 September. The collapse of the Central Powers came swiftly. Bulgaria was the first to sign an armistice, the Armistice of Salonica on 29 September 1918. German Emperor Wilhelm II in a telegram to Bulgarian Tsar Ferdinand I described the situation thus: "Disgraceful! 62,000 Serbs decided the war!". On the same day, the German Supreme Army Command informed Kaiser Wilhelm II and the Imperial Chancellor Count Georg von Hertling , that the military situation facing Germany was hopeless. On 24 October, the Italians began a push that rapidly recovered territory lost after the Battle of Caporetto. This culminated in the Battle of Vittorio Veneto, marking the end of the Austro-Hungarian Army as an effective fighting force. The offensive also triggered the disintegration of the Austro-Hungarian Empire. During the last week of October, declarations of independence were made in Budapest, Prague, and Zagreb. On 29 October, the imperial authorities asked Italy for an armistice, but the Italians continued advancing, reaching Trento, Udine, and Trieste. On 3 November, Austria-Hungary sent a flag of truce to ask for an armistice ( Armistice of Villa Giusti ). The terms, arranged with the Allied Authorities in Paris, were communicated to the Austrian commander and accepted. The Armistice with Austria was signed in the Villa Giusti, near Padua , on 3 November. Austria and Hungary signed separate armistices following the overthrow of the Habsburg monarchy . In the following days, the Italian Army occupied Innsbruck and all Tyrol , with over 20,000 soldiers. On 30 October, the Ottoman Empire capitulated, and signed the Armistice of Mudros. With the military faltering and with widespread loss of confidence in the Kaiser leading to his abdication and fleeing of the country, Germany moved towards surrender. Prince Maximilian of Baden took charge of a new government on October 3 as Chancellor of Germany to negotiate with the Allies. Negotiations with President Wilson began immediately, in the hope that he would offer better terms than the British and French. Wilson demanded a constitutional monarchy and parliamentary control over the German military. In northern Germany, the German Revolution of 1918–1919 began at the end of October 1918. Units of the German Navy refused to set sail for a last, large-scale operation in a war they believed to be as good as lost, initiating the uprising. The sailors' revolt , which then ensued in the naval ports of Wilhelmshaven and Kiel , spread across the whole country within days and led to the proclamation of a republic on 9 November 1918, shortly thereafter to the abdication of Kaiser Wilhelm II , and German surrender. With the military faltering and with widespread loss of confidence in the Kaiser leading to his abdication and fleeing of the country, Germany moved towards surrender. Prince Maximilian of Baden took charge of a new government on October 3 as Chancellor of Germany to negotiate with the Allies. Negotiations with President Wilson began immediately, in the hope that he would offer better terms than the British and French. Wilson demanded a constitutional monarchy and parliamentary control over the German military. In northern Germany, the German Revolution of 1918–1919 began at the end of October 1918. Units of the German Navy refused to set sail for a last, large-scale operation in a war they believed to be as good as lost, initiating the uprising. The sailors' revolt , which then ensued in the naval ports of Wilhelmshaven and Kiel , spread across the whole country within days and led to the proclamation of a republic on 9 November 1918, shortly thereafter to the abdication of Kaiser Wilhelm II , and German surrender. In the aftermath of the war, four empires disappeared: the German, Austro-Hungarian, Ottoman, and Russian. [lower-alpha 14] Numerous nations regained their former independence, and new ones were created. Four dynasties fell as a result of the war: the Romanovs , the Hohenzollerns , the Habsburgs , and the Ottomans . Belgium and Serbia were badly damaged, as was France, with 1.4 million soldiers dead, not counting other casualties. Germany and Russia were similarly affected. A formal state of war between the two sides persisted for another seven months, until the signing of the Treaty of Versailles with Germany on 28 June 1919. The United States Senate did not ratify the treaty despite public support for it, and did not formally end its involvement in the war until the Knox–Porter Resolution was signed on 2 July 1921 by President Warren G. Harding . For the British Empire, the state of war ceased under the provisions of the Termination of the Present War (Definition) Act 1918 concerning: Some war memorials date the end of the war as being when the Versailles Treaty was signed in 1919, which was when many of the troops serving abroad finally returned home; by contrast, most commemorations of the war's end concentrate on the armistice of 11 November 1918. After the war, there grew a certain amount of academic focus on the causes of war and on the elements that could make peace flourish. In part, these led to the institutionalization of peace and conflict studies, security studies and International Relations (IR) in general. The Paris Peace Conference imposed a series of peace treaties on the Central Powers officially ending the war. The 1919 Treaty of Versailles dealt with Germany and, building on Wilson's 14th point , established the League of Nations on 28 June 1919. The Central Powers had to acknowledge responsibility for "all the loss and damage to which the Allied and Associated Governments and their nationals have been subjected as a consequence of the war imposed upon them by" their aggression. In the Treaty of Versailles, this statement was Article 231 . This article became known as the "War Guilt Clause", as the majority of Germans felt humiliated and resentful. Overall, the Germans felt they had been unjustly dealt with by what they called the " diktat of Versailles". German historian Hagen Schulze said the Treaty placed Germany "under legal sanctions, deprived of military power, economically ruined, and politically humiliated." Belgian historian Laurence Van Ypersele emphasises the central role played by memory of the war and the Versailles Treaty in German politics in the 1920s and 1930s: Active denial of war guilt in Germany and German resentment at both reparations and continued Allied occupation of the Rhineland made widespread revision of the meaning and memory of the war problematic. The legend of the " stab in the back " and the wish to revise the "Versailles diktat", and the belief in an international threat aimed at the elimination of the German nation persisted at the heart of German politics. Even a man of peace such as [ Gustav ] Stresemann publicly rejected German guilt. As for the Nazis, they waved the banners of domestic treason and international conspiracy in an attempt to galvanise the German nation into a spirit of revenge. Like a Fascist Italy, Nazi Germany sought to redirect the memory of the war to the benefit of its policies. Meanwhile, new nations liberated from German rule viewed the treaty as a recognition of wrongs committed against small nations by much larger aggressive neighbours. Austria-Hungary was partitioned into several successor states, largely but not entirely along ethnic lines. Apart from Austria and Hungary, Czechoslovakia, Italy, Poland, Romania and Yugoslavia received territories from the Dual Monarchy (the formerly separate and autonomous Kingdom of Croatia-Slavonia was incorporated into Yugoslavia). The details were contained in the Saint-Germain-en-Laye and the Treaty of Trianon . As a result, Hungary lost 64% of its total population, decreasing from 20.9 million to 7.6 million, and losing 31% (3.3 out of 10.7 million) of its ethnic Hungarians . According to the 1910 census, speakers of the Hungarian language included approximately 54% of the entire population of the Kingdom of Hungary . Within the country, numerous ethnic minorities were present: 16.1% Romanians , 10.5% Slovaks , 10.4% Germans , 2.5% Ruthenians , 2.5% Serbs and 8% others. Between 1920 and 1924, 354,000 Hungarians fled former Hungarian territories attached to Romania, Czechoslovakia, and Yugoslavia. The Russian Empire, which withdrew from the war in 1917 after the October Revolution, lost much of its western frontier as the newly independent nations of Estonia , Finland , Latvia , Lithuania , and Poland were carved from it. Romania took control of Bessarabia in April 1918. After 123 years, Poland re-emerged as an independent country. The Kingdom of Serbia and its dynasty, as a "minor Entente nation" and the country with the most casualties per capita, became the backbone of a new multinational state, the Kingdom of Serbs, Croats and Slovenes , later renamed Yugoslavia. Czechoslovakia, combining the Kingdom of Bohemia with parts of the Kingdom of Hungary, became a new nation. Romania would unite all Romanian-speaking people under a single state, leading to Greater Romania . In Australia and New Zealand, the Battle of Gallipoli became known as those nations' "Baptism of Fire". It was the first major war in which the newly established countries fought, and it was one of the first times that Australian troops fought as Australians, not just subjects of the British Crown , and independent national identities for these nations took hold. Anzac Day , commemorating the Australian and New Zealand Army Corps (ANZAC), celebrates this defining moment. In the aftermath of World War I, Greece fought against Turkish nationalists led by Mustafa Kemal , a war that eventually resulted in a massive population exchange between the two countries under the Treaty of Lausanne. According to various sources, several hundred thousand Greeks died during this period, which was tied in with the Greek genocide. A formal state of war between the two sides persisted for another seven months, until the signing of the Treaty of Versailles with Germany on 28 June 1919. The United States Senate did not ratify the treaty despite public support for it, and did not formally end its involvement in the war until the Knox–Porter Resolution was signed on 2 July 1921 by President Warren G. Harding . For the British Empire, the state of war ceased under the provisions of the Termination of the Present War (Definition) Act 1918 concerning: Some war memorials date the end of the war as being when the Versailles Treaty was signed in 1919, which was when many of the troops serving abroad finally returned home; by contrast, most commemorations of the war's end concentrate on the armistice of 11 November 1918. After the war, there grew a certain amount of academic focus on the causes of war and on the elements that could make peace flourish. In part, these led to the institutionalization of peace and conflict studies, security studies and International Relations (IR) in general. The Paris Peace Conference imposed a series of peace treaties on the Central Powers officially ending the war. The 1919 Treaty of Versailles dealt with Germany and, building on Wilson's 14th point , established the League of Nations on 28 June 1919. The Central Powers had to acknowledge responsibility for "all the loss and damage to which the Allied and Associated Governments and their nationals have been subjected as a consequence of the war imposed upon them by" their aggression. In the Treaty of Versailles, this statement was Article 231 . This article became known as the "War Guilt Clause", as the majority of Germans felt humiliated and resentful. Overall, the Germans felt they had been unjustly dealt with by what they called the " diktat of Versailles". German historian Hagen Schulze said the Treaty placed Germany "under legal sanctions, deprived of military power, economically ruined, and politically humiliated." Belgian historian Laurence Van Ypersele emphasises the central role played by memory of the war and the Versailles Treaty in German politics in the 1920s and 1930s: Active denial of war guilt in Germany and German resentment at both reparations and continued Allied occupation of the Rhineland made widespread revision of the meaning and memory of the war problematic. The legend of the " stab in the back " and the wish to revise the "Versailles diktat", and the belief in an international threat aimed at the elimination of the German nation persisted at the heart of German politics. Even a man of peace such as [ Gustav ] Stresemann publicly rejected German guilt. As for the Nazis, they waved the banners of domestic treason and international conspiracy in an attempt to galvanise the German nation into a spirit of revenge. Like a Fascist Italy, Nazi Germany sought to redirect the memory of the war to the benefit of its policies. Meanwhile, new nations liberated from German rule viewed the treaty as a recognition of wrongs committed against small nations by much larger aggressive neighbours. Austria-Hungary was partitioned into several successor states, largely but not entirely along ethnic lines. Apart from Austria and Hungary, Czechoslovakia, Italy, Poland, Romania and Yugoslavia received territories from the Dual Monarchy (the formerly separate and autonomous Kingdom of Croatia-Slavonia was incorporated into Yugoslavia). The details were contained in the Saint-Germain-en-Laye and the Treaty of Trianon . As a result, Hungary lost 64% of its total population, decreasing from 20.9 million to 7.6 million, and losing 31% (3.3 out of 10.7 million) of its ethnic Hungarians . According to the 1910 census, speakers of the Hungarian language included approximately 54% of the entire population of the Kingdom of Hungary . Within the country, numerous ethnic minorities were present: 16.1% Romanians , 10.5% Slovaks , 10.4% Germans , 2.5% Ruthenians , 2.5% Serbs and 8% others. Between 1920 and 1924, 354,000 Hungarians fled former Hungarian territories attached to Romania, Czechoslovakia, and Yugoslavia. The Russian Empire, which withdrew from the war in 1917 after the October Revolution, lost much of its western frontier as the newly independent nations of Estonia , Finland , Latvia , Lithuania , and Poland were carved from it. Romania took control of Bessarabia in April 1918. After 123 years, Poland re-emerged as an independent country. The Kingdom of Serbia and its dynasty, as a "minor Entente nation" and the country with the most casualties per capita, became the backbone of a new multinational state, the Kingdom of Serbs, Croats and Slovenes , later renamed Yugoslavia. Czechoslovakia, combining the Kingdom of Bohemia with parts of the Kingdom of Hungary, became a new nation. Romania would unite all Romanian-speaking people under a single state, leading to Greater Romania . In Australia and New Zealand, the Battle of Gallipoli became known as those nations' "Baptism of Fire". It was the first major war in which the newly established countries fought, and it was one of the first times that Australian troops fought as Australians, not just subjects of the British Crown , and independent national identities for these nations took hold. Anzac Day , commemorating the Australian and New Zealand Army Corps (ANZAC), celebrates this defining moment. In the aftermath of World War I, Greece fought against Turkish nationalists led by Mustafa Kemal , a war that eventually resulted in a massive population exchange between the two countries under the Treaty of Lausanne. According to various sources, several hundred thousand Greeks died during this period, which was tied in with the Greek genocide. Of the 60 million European military personnel who were mobilised from 1914 to 1918, an estimated 8 million were killed , 7 million were permanently disabled, and 15 million were seriously injured. Germany lost 15.1% of its active male population, Austria-Hungary lost 17.1%, and France lost 10.5%. France mobilised 7.8 million men, of which 1.4 million died and 3.2 million were injured. Approximately 15,000 sustained horrific facial injuries, causing social stigma and marginalisation; they were called the gueules cassées . In Germany, civilian deaths were 474,000 higher than in peacetime, due in large part to food shortages and malnutrition that had weakened disease resistance. These excess deaths are estimated as 271,000 in 1918, plus another 71,000 in the first half of 1919 when the blockade was still in effect. Starvation caused by famine killed approximately 100,000 people in Lebanon. Diseases flourished in the chaotic wartime conditions. In 1914 alone, louse-borne epidemic typhus killed 200,000 in Serbia. Starting in early 1918, a major influenza epidemic known as Spanish flu spread around the world, accelerated by the movement of large numbers of soldiers, often crammed together in camps and transport ships with poor sanitation. The Spanish flu killed at least 17 million to 25 million people, including an estimated 2.64 million Europeans and as many as 675,000 Americans. Between 1915 and 1926, an epidemic of encephalitis lethargica spread around the world affecting nearly five million people. 8 million equines including horses , donkeys and mules died, three-quarters of them from the extreme conditions they worked in. The German army was the first to successfully deploy chemical weapons during the Second Battle of Ypres (22 April – 25 May 1915), after German scientists working under the direction of Fritz Haber at the Kaiser Wilhelm Institute developed a method to weaponize chlorine . [lower-alpha 15] The use of chemical weapons had been sanctioned by the German High Command to force Allied soldiers out of their entrenched positions, complementing rather than supplanting more lethal conventional weapons. In time, chemical weapons were deployed by all major belligerents throughout the war, inflicting approximately 1.3 million casualties, of which about 90,000 were fatal. For example, there were an estimated 186,000 British chemical weapons casualties during the war (80% of which were the result of exposure to the vesicant ' mustard gas ', introduced to the battlefield by the Germans in July 1917), and up to one-third of American casualties were caused by them. The Russian Army reportedly suffered roughly 500,000 chemical weapon casualties in World War I. The use of chemical weapons in warfare was a direct violation of the 1899 Hague Declaration Concerning Asphyxiating Gases and the 1907 Hague Convention on Land Warfare , which prohibited their use. The ethnic cleansing of the Ottoman Empire's Armenian population, including mass deportations and executions, during the final years of the Ottoman Empire is considered genocide . The Ottomans carried out organised and systematic massacres of the Armenian population at the beginning of the war and manipulated acts of Armenian resistance by portraying them as rebellions to justify further extermination. In early 1915, several Armenians volunteered to join the Russian forces and the Ottoman government used this as a pretext to issue the Tehcir Law (Law on Deportation), which authorised the deportation of Armenians from the Empire's eastern provinces to Syria between 1915 and 1918. The Armenians were intentionally marched to death and a number were attacked by Ottoman brigands. While an exact number of deaths is unknown, the International Association of Genocide Scholars estimates 1.5 million. The government of Turkey continues to deny the genocide to the present day, arguing that those who died were victims of inter-ethnic fighting, famine, or disease during World War I; these claims are rejected by most historians. Other ethnic groups were similarly attacked by the Ottoman Empire during this period, including Assyrians and Greeks , and some scholars consider those events to be part of the same policy of extermination. At least 250,000 Assyrian Christians, about half of the population, and 350,000–750,000 Anatolian and Pontic Greeks were killed between 1915 and 1922. About eight million soldiers surrendered and were held in POW camps during the war. All nations pledged to follow the Hague Conventions on fair treatment of prisoners of war , and the survival rate for POWs was generally much higher than that of combatants at the front. 25–31% of Russian losses (as a proportion of those captured, wounded, or killed) were to prisoner status, for Austria-Hungary 32%, for Italy 26%, for France 12%, for Germany 9%; for Britain 7%. Prisoners from the Allied armies totalled about 1.4 million (not including Russia, which lost 2.5–3.5 million soldiers as prisoners). From the Central Powers, about 3.3 million soldiers became prisoners; most of them surrendered to Russians. The German army was the first to successfully deploy chemical weapons during the Second Battle of Ypres (22 April – 25 May 1915), after German scientists working under the direction of Fritz Haber at the Kaiser Wilhelm Institute developed a method to weaponize chlorine . [lower-alpha 15] The use of chemical weapons had been sanctioned by the German High Command to force Allied soldiers out of their entrenched positions, complementing rather than supplanting more lethal conventional weapons. In time, chemical weapons were deployed by all major belligerents throughout the war, inflicting approximately 1.3 million casualties, of which about 90,000 were fatal. For example, there were an estimated 186,000 British chemical weapons casualties during the war (80% of which were the result of exposure to the vesicant ' mustard gas ', introduced to the battlefield by the Germans in July 1917), and up to one-third of American casualties were caused by them. The Russian Army reportedly suffered roughly 500,000 chemical weapon casualties in World War I. The use of chemical weapons in warfare was a direct violation of the 1899 Hague Declaration Concerning Asphyxiating Gases and the 1907 Hague Convention on Land Warfare , which prohibited their use. The ethnic cleansing of the Ottoman Empire's Armenian population, including mass deportations and executions, during the final years of the Ottoman Empire is considered genocide . The Ottomans carried out organised and systematic massacres of the Armenian population at the beginning of the war and manipulated acts of Armenian resistance by portraying them as rebellions to justify further extermination. In early 1915, several Armenians volunteered to join the Russian forces and the Ottoman government used this as a pretext to issue the Tehcir Law (Law on Deportation), which authorised the deportation of Armenians from the Empire's eastern provinces to Syria between 1915 and 1918. The Armenians were intentionally marched to death and a number were attacked by Ottoman brigands. While an exact number of deaths is unknown, the International Association of Genocide Scholars estimates 1.5 million. The government of Turkey continues to deny the genocide to the present day, arguing that those who died were victims of inter-ethnic fighting, famine, or disease during World War I; these claims are rejected by most historians. Other ethnic groups were similarly attacked by the Ottoman Empire during this period, including Assyrians and Greeks , and some scholars consider those events to be part of the same policy of extermination. At least 250,000 Assyrian Christians, about half of the population, and 350,000–750,000 Anatolian and Pontic Greeks were killed between 1915 and 1922. The German army was the first to successfully deploy chemical weapons during the Second Battle of Ypres (22 April – 25 May 1915), after German scientists working under the direction of Fritz Haber at the Kaiser Wilhelm Institute developed a method to weaponize chlorine . [lower-alpha 15] The use of chemical weapons had been sanctioned by the German High Command to force Allied soldiers out of their entrenched positions, complementing rather than supplanting more lethal conventional weapons. In time, chemical weapons were deployed by all major belligerents throughout the war, inflicting approximately 1.3 million casualties, of which about 90,000 were fatal. For example, there were an estimated 186,000 British chemical weapons casualties during the war (80% of which were the result of exposure to the vesicant ' mustard gas ', introduced to the battlefield by the Germans in July 1917), and up to one-third of American casualties were caused by them. The Russian Army reportedly suffered roughly 500,000 chemical weapon casualties in World War I. The use of chemical weapons in warfare was a direct violation of the 1899 Hague Declaration Concerning Asphyxiating Gases and the 1907 Hague Convention on Land Warfare , which prohibited their use. The ethnic cleansing of the Ottoman Empire's Armenian population, including mass deportations and executions, during the final years of the Ottoman Empire is considered genocide . The Ottomans carried out organised and systematic massacres of the Armenian population at the beginning of the war and manipulated acts of Armenian resistance by portraying them as rebellions to justify further extermination. In early 1915, several Armenians volunteered to join the Russian forces and the Ottoman government used this as a pretext to issue the Tehcir Law (Law on Deportation), which authorised the deportation of Armenians from the Empire's eastern provinces to Syria between 1915 and 1918. The Armenians were intentionally marched to death and a number were attacked by Ottoman brigands. While an exact number of deaths is unknown, the International Association of Genocide Scholars estimates 1.5 million. The government of Turkey continues to deny the genocide to the present day, arguing that those who died were victims of inter-ethnic fighting, famine, or disease during World War I; these claims are rejected by most historians. Other ethnic groups were similarly attacked by the Ottoman Empire during this period, including Assyrians and Greeks , and some scholars consider those events to be part of the same policy of extermination. At least 250,000 Assyrian Christians, about half of the population, and 350,000–750,000 Anatolian and Pontic Greeks were killed between 1915 and 1922. About eight million soldiers surrendered and were held in POW camps during the war. All nations pledged to follow the Hague Conventions on fair treatment of prisoners of war , and the survival rate for POWs was generally much higher than that of combatants at the front. 25–31% of Russian losses (as a proportion of those captured, wounded, or killed) were to prisoner status, for Austria-Hungary 32%, for Italy 26%, for France 12%, for Germany 9%; for Britain 7%. Prisoners from the Allied armies totalled about 1.4 million (not including Russia, which lost 2.5–3.5 million soldiers as prisoners). From the Central Powers, about 3.3 million soldiers became prisoners; most of them surrendered to Russians. Allied personnel was around 42,928,000, while Central personnel was near 25,248,000. The British soldiers of the war were initially volunteers but increasingly were conscripted . Surviving veterans, returning home, often found they could discuss their experiences only among themselves. Grouping, they formed "veterans' associations" or "Legions". A small number of personal accounts of American veterans have been collected by the Library of Congress Veterans History Project . Conscription was common in most European countries. However, it was controversial in English-speaking countries. It was especially unpopular among minority ethnicities—especially the Irish Catholics in Ireland, Australia, and the French Catholics in Canada. In the United States, conscription began in 1917 and was generally well-received, with a few pockets of opposition in isolated rural areas. The administration decided to rely primarily on conscription, rather than voluntary enlistment, to raise military manpower after only 73,000 volunteers enlisted out of the initial 1 million target in the first six weeks of the war. Military and civilian observers from every major power closely followed the course of the war. Many were able to report on events from a perspective somewhat akin to modern " embedded " positions within the opposing land and naval forces.Conscription was common in most European countries. However, it was controversial in English-speaking countries. It was especially unpopular among minority ethnicities—especially the Irish Catholics in Ireland, Australia, and the French Catholics in Canada. In the United States, conscription began in 1917 and was generally well-received, with a few pockets of opposition in isolated rural areas. The administration decided to rely primarily on conscription, rather than voluntary enlistment, to raise military manpower after only 73,000 volunteers enlisted out of the initial 1 million target in the first six weeks of the war. Military and civilian observers from every major power closely followed the course of the war. Many were able to report on events from a perspective somewhat akin to modern " embedded " positions within the opposing land and naval forces.Macro- and micro-economic consequences devolved from the war. Families were altered by the departure of many men. With the death or absence of the primary wage earner, women were forced into the workforce in unprecedented numbers. At the same time, the industry needed to replace the lost labourers sent to war. This aided the struggle for voting rights for women . In all nations, the government's share of GDP increased, surpassing 50% in both Germany and France and nearly reaching that level in Britain. To pay for purchases in the United States, Britain cashed in its extensive investments in American railroads and then began borrowing heavily from Wall Street . President Wilson was on the verge of cutting off the loans in late 1916 but allowed a great increase in US government lending to the Allies. After 1919, the US demanded repayment of these loans. The repayments were, in part, funded by German reparations that, in turn, were supported by American loans to Germany. This circular system collapsed in 1931 and some loans were never repaid. Britain still owed the United States $4.4 billion [lower-alpha 16] of World War I debt in 1934; the last installment was finally paid in 2015. Britain turned to her colonies for help in obtaining essential war materials whose supply from traditional sources had become difficult. Geologists such as Albert Kitson were called on to find new resources of precious minerals in the African colonies. Kitson discovered important new deposits of manganese , used in munitions production, in the Gold Coast . Article 231 of the Treaty of Versailles (the so-called "war guilt" clause) stated Germany accepted responsibility for "all the loss and damage to which the Allied and Associated Governments and their nationals have been subjected as a consequence of the war imposed upon them by the aggression of Germany and her allies." It was worded as such to lay a legal basis for reparations, and a similar clause was inserted in the treaties with Austria and Hungary. However, neither of them interpreted it as an admission of war guilt." In 1921, the total reparation sum was placed at 132 billion gold marks. However, "Allied experts knew that Germany could not pay" this sum. The total sum was divided into three categories, with the third being "deliberately designed to be chimerical" and its "primary function was to mislead public opinion ... into believing the "total sum was being maintained." Thus, 50 billion gold marks (12.5 billion dollars) "represented the actual Allied assessment of German capacity to pay" and "therefore … represented the total German reparations" figure that had to be paid. This figure could be paid in cash or in-kind (coal, timber, chemical dyes, etc.). In addition, some of the territory lost—via the Treaty of Versailles—was credited towards the reparation figure as were other acts such as helping to restore the Library of Louvain. By 1929, the Great Depression arrived, causing political chaos throughout the world. In 1932 the payment of reparations was suspended by the international community, by which point Germany had paid only the equivalent of 20.598 billion gold marks in reparations. With the rise of Adolf Hitler, all bonds and loans that had been issued and taken out during the 1920s and early 1930s were cancelled. David Andelman notes "Refusing to pay doesn't make an agreement null and void. The bonds, the agreement, still exist." Thus, following the Second World War, at the London Conference in 1953, Germany agreed to resume payment on the money borrowed. On 3 October 2010, Germany made the final payment on these bonds. [lower-alpha 17] The Australian prime minister, Billy Hughes , wrote to the British prime minister, David Lloyd George , "You have assured us that you cannot get better terms. I much regret it, and hope even now that some way may be found of securing agreement for demanding reparation commensurate with the tremendous sacrifices made by the British Empire and her Allies." Australia received £5,571,720 in war reparations, but the direct cost of the war to Australia had been £376,993,052, and, by the mid-1930s, repatriation pensions, war gratuities, interest and sinking fund charges were £831,280,947. Of about 416,000 Australians who served, about 60,000 were killed and another 152,000 were wounded. The war contributed to the evolution of the wristwatch from women's jewellery to a practical everyday item, replacing the pocketwatch , which requires a free hand to operate. Trench watches were designed for use by the military as pocket watches were not as effective for combat. Military funding of advancements in radio contributed to the post-war popularity of the medium. In the Balkans, Yugoslav nationalists such as the leader, Ante Trumbić , strongly supported the war, desiring the freedom of Yugoslavs from Austria-Hungary and other foreign powers and the creation of an independent Yugoslavia. The Yugoslav Committee , led by Trumbić, was formed in Paris on 30 April 1915 but shortly moved its office to London. In April 1918, the Rome Congress of Oppressed Nationalities met, including Czechoslovak , Italian, Polish , Transylvanian , and Yugoslav representatives who urged the Allies to support national self-determination for the peoples residing within Austria-Hungary. In the Middle East, Arab nationalism soared in Ottoman territories in response to the rise of Turkish nationalism during the war, with Arab nationalist leaders advocating the creation of a pan-Arab state. In 1916, the Arab Revolt began in Ottoman-controlled territories of the Middle East to achieve independence. In East Africa, Iyasu V of Ethiopia was supporting the Dervish state who were at war with the British in the Somaliland campaign . Von Syburg, the German envoy in Addis Ababa , said, "now the time has come for Ethiopia to regain the coast of the Red Sea driving the Italians home, to restore the Empire to its ancient size." The Ethiopian Empire was on the verge of entering World War I on the side of the Central Powers before Iyasu's overthrow at the Battle of Segale due to Allied pressure on the Ethiopian aristocracy. Iyasu was accused of converting to Islam . According to Ethiopian historian Bahru Zewde , the evidence used to prove Iyasu's conversion was a doctored photo of Iyasu wearing a turban provided by the Allies. Some historians claim the British spy T. E. Lawrence forged the photo. Several socialist parties initially supported the war when it began in August 1914. But European socialists split on national lines, with the concept of class conflict held by radical socialists such as Marxists and syndicalists being overborne by their patriotic support for the war. Once the war began, Austrian, British, French, German, and Russian socialists followed the rising nationalist current by supporting their countries' intervention in the war. Italian nationalism was stirred by the outbreak of the war and was initially strongly supported by a variety of political factions. One of the most prominent and popular Italian nationalist supporters of the war was Gabriele D'Annunzio , who promoted Italian irredentism and helped sway the Italian public to support intervention in the war. The Italian Liberal Party , under the leadership of Paolo Boselli , promoted intervention in the war on the side of the Allies and used the Dante Alighieri Society to promote Italian nationalism. Italian socialists were divided on whether to support the war or oppose it; some were militant supporters of the war, including Benito Mussolini and Leonida Bissolati . However, the Italian Socialist Party decided to oppose the war after anti-militarist protestors were killed, resulting in a general strike called Red Week . The Italian Socialist Party purged itself of pro-war nationalist members, including Mussolini. Mussolini, a syndicalist who supported the war on grounds of irredentist claims on Italian-populated regions of Austria-Hungary, formed the pro-interventionist Il Popolo d'Italia and the Fasci Rivoluzionario d'Azione Internazionalista ("Revolutionary Fasci for International Action") in October 1914 that later developed into the Fasci Italiani di Combattimento in 1919, the origin of fascism. Mussolini's nationalism enabled him to raise funds from Ansaldo (an armaments firm) and other companies to create Il Popolo d'Italia to convince socialists and revolutionaries to support the war. On both sides, there was large-scale fundraising for soldiers' welfare, their dependents and those injured. The Nail Men were a German example. Around the British Empire, there were many patriotic funds, including the Royal Patriotic Fund Corporation , Canadian Patriotic Fund , Queensland Patriotic Fund and, by 1919, there were 983 funds in New Zealand. At the start of the next world war the New Zealand funds were reformed, having been criticised as overlapping, wasteful and abused, but 11 were still functioning in 2002. Many countries jailed those who spoke out against the conflict. These included Eugene Debs in the United States and Bertrand Russell in Britain. In the US, the Espionage Act of 1917 and Sedition Act of 1918 made it a federal crime to oppose military recruitment or make any statements deemed "disloyal". Publications at all critical of the government were removed from circulation by postal censors, and many served long prison sentences for statements of fact deemed unpatriotic. Several nationalists opposed intervention, particularly within states that the nationalists were hostile to. Although the vast majority of Irish people consented to participate in the war in 1914 and 1915, a minority of advanced Irish nationalists had staunchly opposed taking part. The war began amid the Home Rule crisis in Ireland that had resurfaced in 1912, and by July 1914 there was a serious possibility of an outbreak of civil war in Ireland. Irish nationalists and Marxists attempted to pursue Irish independence, culminating in the Easter Rising of 1916, with Germany sending 20,000 rifles to Ireland to stir unrest in Britain. The UK government placed Ireland under martial law in response to the Easter Rising, though once the immediate threat of revolution had dissipated, the authorities did try to make concessions to nationalist feeling. However, opposition to involvement in the war increased in Ireland, resulting in the Conscription Crisis of 1918 . Other opposition came from conscientious objectors —some socialist, some religious—who had refused to fight. In Britain, 16,000 people asked for conscientious objector status. Some of them, most notably prominent peace activist Stephen Hobhouse , refused both military and alternative service . Many suffered years of prison, including solitary confinement and bread and water diets. Even after the war, in Britain, many job advertisements were marked "No conscientious objectors need to apply". On 1–4 May 1917, about 100,000 workers and soldiers of Petrograd , and after them, the workers and soldiers of other Russian cities, led by the Bolsheviks, demonstrated under banners reading "Down with the war!" and "all power to the Soviets!" The mass demonstrations resulted in a crisis for the Russian Provisional Government . In Milan , in May 1917, Bolshevik revolutionaries organised and engaged in rioting calling for an end to the war, and managed to close down factories and stop public transportation. The Italian army was forced to enter Milan with tanks and machine guns to face Bolsheviks and anarchists , who fought violently until May 23 when the army gained control of the city. Almost 50 people (including three Italian soldiers) were killed and over 800 people were arrested. In the Balkans, Yugoslav nationalists such as the leader, Ante Trumbić , strongly supported the war, desiring the freedom of Yugoslavs from Austria-Hungary and other foreign powers and the creation of an independent Yugoslavia. The Yugoslav Committee , led by Trumbić, was formed in Paris on 30 April 1915 but shortly moved its office to London. In April 1918, the Rome Congress of Oppressed Nationalities met, including Czechoslovak , Italian, Polish , Transylvanian , and Yugoslav representatives who urged the Allies to support national self-determination for the peoples residing within Austria-Hungary. In the Middle East, Arab nationalism soared in Ottoman territories in response to the rise of Turkish nationalism during the war, with Arab nationalist leaders advocating the creation of a pan-Arab state. In 1916, the Arab Revolt began in Ottoman-controlled territories of the Middle East to achieve independence. In East Africa, Iyasu V of Ethiopia was supporting the Dervish state who were at war with the British in the Somaliland campaign . Von Syburg, the German envoy in Addis Ababa , said, "now the time has come for Ethiopia to regain the coast of the Red Sea driving the Italians home, to restore the Empire to its ancient size." The Ethiopian Empire was on the verge of entering World War I on the side of the Central Powers before Iyasu's overthrow at the Battle of Segale due to Allied pressure on the Ethiopian aristocracy. Iyasu was accused of converting to Islam . According to Ethiopian historian Bahru Zewde , the evidence used to prove Iyasu's conversion was a doctored photo of Iyasu wearing a turban provided by the Allies. Some historians claim the British spy T. E. Lawrence forged the photo. Several socialist parties initially supported the war when it began in August 1914. But European socialists split on national lines, with the concept of class conflict held by radical socialists such as Marxists and syndicalists being overborne by their patriotic support for the war. Once the war began, Austrian, British, French, German, and Russian socialists followed the rising nationalist current by supporting their countries' intervention in the war. Italian nationalism was stirred by the outbreak of the war and was initially strongly supported by a variety of political factions. One of the most prominent and popular Italian nationalist supporters of the war was Gabriele D'Annunzio , who promoted Italian irredentism and helped sway the Italian public to support intervention in the war. The Italian Liberal Party , under the leadership of Paolo Boselli , promoted intervention in the war on the side of the Allies and used the Dante Alighieri Society to promote Italian nationalism. Italian socialists were divided on whether to support the war or oppose it; some were militant supporters of the war, including Benito Mussolini and Leonida Bissolati . However, the Italian Socialist Party decided to oppose the war after anti-militarist protestors were killed, resulting in a general strike called Red Week . The Italian Socialist Party purged itself of pro-war nationalist members, including Mussolini. Mussolini, a syndicalist who supported the war on grounds of irredentist claims on Italian-populated regions of Austria-Hungary, formed the pro-interventionist Il Popolo d'Italia and the Fasci Rivoluzionario d'Azione Internazionalista ("Revolutionary Fasci for International Action") in October 1914 that later developed into the Fasci Italiani di Combattimento in 1919, the origin of fascism. Mussolini's nationalism enabled him to raise funds from Ansaldo (an armaments firm) and other companies to create Il Popolo d'Italia to convince socialists and revolutionaries to support the war. On both sides, there was large-scale fundraising for soldiers' welfare, their dependents and those injured. The Nail Men were a German example. Around the British Empire, there were many patriotic funds, including the Royal Patriotic Fund Corporation , Canadian Patriotic Fund , Queensland Patriotic Fund and, by 1919, there were 983 funds in New Zealand. At the start of the next world war the New Zealand funds were reformed, having been criticised as overlapping, wasteful and abused, but 11 were still functioning in 2002. On both sides, there was large-scale fundraising for soldiers' welfare, their dependents and those injured. The Nail Men were a German example. Around the British Empire, there were many patriotic funds, including the Royal Patriotic Fund Corporation , Canadian Patriotic Fund , Queensland Patriotic Fund and, by 1919, there were 983 funds in New Zealand. At the start of the next world war the New Zealand funds were reformed, having been criticised as overlapping, wasteful and abused, but 11 were still functioning in 2002. Many countries jailed those who spoke out against the conflict. These included Eugene Debs in the United States and Bertrand Russell in Britain. In the US, the Espionage Act of 1917 and Sedition Act of 1918 made it a federal crime to oppose military recruitment or make any statements deemed "disloyal". Publications at all critical of the government were removed from circulation by postal censors, and many served long prison sentences for statements of fact deemed unpatriotic. Several nationalists opposed intervention, particularly within states that the nationalists were hostile to. Although the vast majority of Irish people consented to participate in the war in 1914 and 1915, a minority of advanced Irish nationalists had staunchly opposed taking part. The war began amid the Home Rule crisis in Ireland that had resurfaced in 1912, and by July 1914 there was a serious possibility of an outbreak of civil war in Ireland. Irish nationalists and Marxists attempted to pursue Irish independence, culminating in the Easter Rising of 1916, with Germany sending 20,000 rifles to Ireland to stir unrest in Britain. The UK government placed Ireland under martial law in response to the Easter Rising, though once the immediate threat of revolution had dissipated, the authorities did try to make concessions to nationalist feeling. However, opposition to involvement in the war increased in Ireland, resulting in the Conscription Crisis of 1918 . Other opposition came from conscientious objectors —some socialist, some religious—who had refused to fight. In Britain, 16,000 people asked for conscientious objector status. Some of them, most notably prominent peace activist Stephen Hobhouse , refused both military and alternative service . Many suffered years of prison, including solitary confinement and bread and water diets. Even after the war, in Britain, many job advertisements were marked "No conscientious objectors need to apply". On 1–4 May 1917, about 100,000 workers and soldiers of Petrograd , and after them, the workers and soldiers of other Russian cities, led by the Bolsheviks, demonstrated under banners reading "Down with the war!" and "all power to the Soviets!" The mass demonstrations resulted in a crisis for the Russian Provisional Government . In Milan , in May 1917, Bolshevik revolutionaries organised and engaged in rioting calling for an end to the war, and managed to close down factories and stop public transportation. The Italian army was forced to enter Milan with tanks and machine guns to face Bolsheviks and anarchists , who fought violently until May 23 when the army gained control of the city. Almost 50 people (including three Italian soldiers) were killed and over 800 people were arrested. World War I began as a clash of 20th-century technology and 19th-century tactics , with the inevitably large ensuing casualties. By the end of 1917, however, the major armies, now numbering millions of men, had modernised and were making use of telephone, wireless communication , armoured cars , tanks (especially with the advent of the prototype tank, Little Willie ), and aircraft. Artillery also underwent a revolution. In 1914, cannons were positioned in the front line and fired directly at their targets. By 1917, indirect fire with guns (as well as mortars and even machine guns) was commonplace, using new techniques for spotting and ranging, notably, aircraft and the often overlooked field telephone . Fixed-wing aircraft were initially used for reconnaissance and ground attack . To shoot down enemy planes, anti-aircraft guns and fighter aircraft were developed. Strategic bombers were created, principally by the Germans and British, though the former used Zeppelins as well. Towards the end of the conflict, aircraft carriers were used for the first time, with HMS Furious launching Sopwith Camels in a raid to destroy the Zeppelin hangars at Tønder in 1918. The non-military diplomatic and propaganda interactions among the nations were designed to build support for the cause or to undermine support for the enemy. For the most part, wartime diplomacy focused on five issues: propaganda campaigns ; defining and redefining the war goals, which became harsher as the war went on; luring neutral nations (Italy, Ottoman Empire, Bulgaria, Romania) into the coalition by offering slices of enemy territory; and encouragement by the Allies of nationalistic minority movements inside the Central Powers, especially among Czechs, Poles, and Arabs. In addition, multiple peace proposals were coming from neutrals, or one side or the other; none of them progressed very far. Memorials were built in thousands of villages and towns. Close to battlefields, those buried in improvised burial grounds were gradually moved to formal graveyards under the care of organisations such as the Commonwealth War Graves Commission , the American Battle Monuments Commission , the German War Graves Commission , and Le Souvenir français . Many of these graveyards also have monuments to the missing or unidentified dead, such as the Menin Gate Memorial to the Missing and the Thiepval Memorial to the Missing of the Somme . In 1915, John McCrae , a Canadian army doctor, wrote the poem In Flanders Fields as a salute to those who perished in the war. Published in Punch on 8 December 1915, it is still recited today, especially on Remembrance Day and Memorial Day . National World War I Museum and Memorial in Kansas City, Missouri , is a memorial dedicated to all Americans who served in World War I. The Liberty Memorial was dedicated on 1 November 1921, when the supreme Allied commanders spoke to a crowd of more than 100,000 people. The UK Government has budgeted substantial resources to the commemoration of the war during the period 2014 to 2018 . The lead body is the Imperial War Museum . On 3 August 2014, French President François Hollande and German President Joachim Gauck together marked the centenary of Germany's declaration of war on France by laying the first stone of a memorial in Vieil Armand, known in German as Hartmannswillerkopf , for French and German soldiers killed in the war. During the Armistice centenary commemorations , French President Emmanuel Macron and German Chancellor Angela Merkel visited the site of the signing of the Armistice of Compiègne and unveiled a plaque to reconciliation. ... "Strange, friend," I said, "Here is no cause to mourn." "None," said the other, "Save the undone years"... The first tentative efforts to comprehend the meaning and consequences of modern warfare began during the initial phases of the war; this process continued throughout and after the end of hostilities and is still underway more than a century later. Teaching World War I has presented special challenges. When compared with World War II , the First World War is often thought to be "a wrong war fought for the wrong reasons"; it lacks the metanarrative of good versus evil that characterizes retellings of the Second World War. Lacking recognizable heroes and villains, it is often taught thematically, invoking tropes like the wastefulness of war, the folly of generals and the innocence of soldiers. The complexity of the conflict is mostly obscured by these oversimplifications. George Kennan referred to the war as the "seminal catastrophe of the 20th century". Historian Heather Jones argues that the historiography has been reinvigorated by a cultural turn in the 21st century. Scholars have raised entirely new questions regarding military occupation , radicalisation of politics, race , medical science , gender and mental health . Among the major subjects that historians have long debated regarding the war include: Why the war began ; why the Allies won; whether generals were responsible for high casualty rates ; how soldiers endured the poor conditions of trench warfare ; and to what extent the civilian home front accepted and endorsed the war effort. As late as 2007, signs warning visitors to keep off certain paths at battlefield sites like Verdun and Somme remained in place as unexploded ordnance continued to pose a danger. In France and Belgium locals who discover caches of unexploded munitions are assisted by weapons disposal units. In some places, plant life has still not returned to normal. Memorials were built in thousands of villages and towns. Close to battlefields, those buried in improvised burial grounds were gradually moved to formal graveyards under the care of organisations such as the Commonwealth War Graves Commission , the American Battle Monuments Commission , the German War Graves Commission , and Le Souvenir français . Many of these graveyards also have monuments to the missing or unidentified dead, such as the Menin Gate Memorial to the Missing and the Thiepval Memorial to the Missing of the Somme . In 1915, John McCrae , a Canadian army doctor, wrote the poem In Flanders Fields as a salute to those who perished in the war. Published in Punch on 8 December 1915, it is still recited today, especially on Remembrance Day and Memorial Day . National World War I Museum and Memorial in Kansas City, Missouri , is a memorial dedicated to all Americans who served in World War I. The Liberty Memorial was dedicated on 1 November 1921, when the supreme Allied commanders spoke to a crowd of more than 100,000 people. The UK Government has budgeted substantial resources to the commemoration of the war during the period 2014 to 2018 . The lead body is the Imperial War Museum . On 3 August 2014, French President François Hollande and German President Joachim Gauck together marked the centenary of Germany's declaration of war on France by laying the first stone of a memorial in Vieil Armand, known in German as Hartmannswillerkopf , for French and German soldiers killed in the war. During the Armistice centenary commemorations , French President Emmanuel Macron and German Chancellor Angela Merkel visited the site of the signing of the Armistice of Compiègne and unveiled a plaque to reconciliation. ... "Strange, friend," I said, "Here is no cause to mourn." "None," said the other, "Save the undone years"... The first tentative efforts to comprehend the meaning and consequences of modern warfare began during the initial phases of the war; this process continued throughout and after the end of hostilities and is still underway more than a century later. Teaching World War I has presented special challenges. When compared with World War II , the First World War is often thought to be "a wrong war fought for the wrong reasons"; it lacks the metanarrative of good versus evil that characterizes retellings of the Second World War. Lacking recognizable heroes and villains, it is often taught thematically, invoking tropes like the wastefulness of war, the folly of generals and the innocence of soldiers. The complexity of the conflict is mostly obscured by these oversimplifications. George Kennan referred to the war as the "seminal catastrophe of the 20th century". Historian Heather Jones argues that the historiography has been reinvigorated by a cultural turn in the 21st century. Scholars have raised entirely new questions regarding military occupation , radicalisation of politics, race , medical science , gender and mental health . Among the major subjects that historians have long debated regarding the war include: Why the war began ; why the Allies won; whether generals were responsible for high casualty rates ; how soldiers endured the poor conditions of trench warfare ; and to what extent the civilian home front accepted and endorsed the war effort. As late as 2007, signs warning visitors to keep off certain paths at battlefield sites like Verdun and Somme remained in place as unexploded ordnance continued to pose a danger. In France and Belgium locals who discover caches of unexploded munitions are assisted by weapons disposal units. In some places, plant life has still not returned to normal.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/2023–2024_Zimbabwe_cholera_outbreak/html

2023–2024 Zimbabwe cholera outbreak

A cholera outbreak started in Buhera District , Manicaland , Zimbabwe . The outbreak is thought to have started on 12 February 2023. As of now it has a geographic coverage of 45 out of 62 districts.First cholera case was reported in Buhera District in Manicaland on the 12 February, 2023. The Ministry of Health and Child Care reported that there were 152 recorded cases and 12 deaths reported in August 2023 alone in Buhera. It was also reported in Hwedza District in Mashonaland East . As of 5 October 2023, the suspected cases and deaths were at 4609 and 100 respectively, confirmed at 935 cases while death toll at 30. On the 17 November 2023, the central government announced a state of emergency in Harare metropolitan. It now have a geographic coverage of 45 out of 62 districts.In response to the outbreak, the Zimbabwean government imposed restrictions on gatherings; funeral attendees were limited to 50 people, and no food could be served. People were advised to avoid physical contact and social events, as well as to maintain proper hygiene. Zimbabwe banned large gatherings in October in response to outbreak.

Wiki

Cholera

https://api.wikimedia.org/core/v1/wikipedia/en/page/1863–1875_cholera_pandemic/html

1863–1875 cholera pandemic

The fourth cholera pandemic of the 19th century began in the Ganges Delta of the Bengal region and traveled with Muslim pilgrims to Mecca . In its first year, the epidemic claimed 30,000 of 90,000 pilgrims. Cholera spread throughout the Middle East and was carried to the Russian Empire , Europe, Africa, and North America, in each case spreading via travelers from port cities and along inland waterways. [ citation needed ] The pandemic reached Northern Africa in 1865 and spread to sub-Saharan Africa, killing 70,000 in Zanzibar in 1869–70. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have taken 165,000 lives in the Austrian Empire , including 30,000 each in Hungary and Belgium , and 20,000 in the Netherlands . In June 1866, a localized epidemic in the East End of London claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems ; the East End section was not quite complete. It was also caused by the city's overcrowding in the East End, which helped the disease to spread more quickly in the area. Epidemiologist William Farr identified the East London Water Company as the source of the contamination. Farr made use of prior work by John Snow and others, pointing to contaminated drinking water as the likely cause of cholera in an 1854 outbreak . In the same year, the use of contaminated canal water in local water works caused a minor outbreak at Ystalyfera in South Wales. Workers associated with the company, and their families, were most affected, and 119 died. [ citation needed ] The deaths of more than 1,100 people in New York City in 1866 resulted in the establishment of the New York Metropolitan Board of Health . In 1867, Italy lost 113,000 to cholera, and 80,000 died of the disease in Algeria . Outbreaks in North America in the 1870s killed some 50,000 Americans as cholera spread from New Orleans via passengers along the Mississippi River and to ports on its tributaries.

Wiki

Cholera

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

Chicago

Chicago [lower-alpha 1] is the most populous city in the U.S. state of Illinois and in the Midwestern United States . With a population of 2,746,388 in the 2020 census , it is the third-most populous city in the United States after New York City and Los Angeles . As the seat of Cook County , the second-most populous county in the U.S., Chicago is the center of the Chicago metropolitan area , often colloquially called "Chicagoland" and home to 9.6 million residents. Located on the shore of Lake Michigan , Chicago was incorporated as a city in 1837 near a portage between the Great Lakes and the Mississippi River watershed . It grew rapidly in the mid-19th century. In 1871, the Great Chicago Fire destroyed several square miles and left more than 100,000 homeless, but Chicago's population continued to grow. Chicago made noted contributions to urban planning and architecture , such as the Chicago School , the development of the City Beautiful Movement , and the steel-framed skyscraper . Chicago is an international hub for finance, culture , commerce, industry, education, technology, telecommunications, and transportation . It has the largest and most diverse derivatives market in the world, generating 20% of all volume in commodities and financial futures alone. O'Hare International Airport is routinely ranked among the world's top six busiest airports by passenger traffic , and the region is also the nation's railroad hub. The Chicago area has one of the highest gross domestic products (GDP) of any urban region in the world, generating $689 billion in 2018. Chicago's economy is diverse , with no single industry employing more than 14% of the workforce. Chicago is a major destination for tourism , including visitors to its cultural institutions , and Lake Michigan beaches . Chicago's culture has contributed much to the visual arts, literature , film, theater , comedy (especially improvisational comedy ), food , dance, and music (particularly jazz , blues , soul , hip-hop , gospel , and electronic dance music , including house music ). Chicago is home to the Chicago Symphony Orchestra and the Lyric Opera of Chicago , while the Art Institute of Chicago provides an influential visual arts museum and art school . The Chicago area also hosts the University of Chicago , Northwestern University , and the University of Illinois Chicago , among other institutions of learning . Professional sports in Chicago include all major professional leagues , including two Major League Baseball teams.The name Chicago is derived from a French rendering of the indigenous Miami-Illinois word shikaakwa for a wild relative of the onion ; it is known to botanists as Allium tricoccum and known more commonly as "ramps". The first known reference to the site of the current city of Chicago as " Checagou " was by Robert de LaSalle around 1679 in a memoir. Henri Joutel , in his journal of 1688, noted that the eponymous wild "garlic" grew profusely in the area. According to his diary of late September 1687: ... when we arrived at the said place called "Chicagou" which, according to what we were able to learn of it, has taken this name because of the quantity of garlic which grows in the forests in this region. The city has had several nicknames throughout its history, such as the Windy City , Chi-Town, Second City, and City of the Big Shoulders. In the mid-18th century, the area was inhabited by the Potawatomi , an indigenous tribe who had succeeded the Miami and Sauk and Fox peoples in this region. The first known permanent settler in Chicago was trader Jean Baptiste Point du Sable . Du Sable was of African descent, perhaps born in the French colony of Saint-Domingue (Haiti), and established the settlement in the 1780s. He is commonly known as the "Founder of Chicago". In 1795, following the victory of the new United States in the Northwest Indian War , an area that was to be part of Chicago was turned over to the U.S. for a military post by native tribes in accordance with the Treaty of Greenville . In 1803, the U.S. Army constructed Fort Dearborn , which was destroyed during the War of 1812 in the Battle of Fort Dearborn by the Potawatomi before being later rebuilt. After the War of 1812, the Ottawa , Ojibwe , and Potawatomi tribes ceded additional land to the United States in the 1816 Treaty of St. Louis . The Potawatomi were forcibly removed from their land after the 1833 Treaty of Chicago and sent west of the Mississippi River as part of the federal policy of Indian removal . On August 12, 1833, the Town of Chicago was organized with a population of about 200. Within seven years it grew to more than 6,000 people. On June 15, 1835, the first public land sales began with Edmund Dick Taylor as Receiver of Public Monies. The City of Chicago was incorporated on Saturday, March 4, 1837, and for several decades was the world's fastest-growing city. As the site of the Chicago Portage , the city became an important transportation hub between the eastern and western United States. Chicago's first railway, Galena and Chicago Union Railroad , and the Illinois and Michigan Canal opened in 1848. The canal allowed steamboats and sailing ships on the Great Lakes to connect to the Mississippi River. A flourishing economy brought residents from rural communities and immigrants from abroad. Manufacturing and retail and finance sectors became dominant, influencing the American economy . The Chicago Board of Trade (established 1848) listed the first-ever standardized "exchange-traded" forward contracts, which were called futures contracts . In the 1850s, Chicago gained national political prominence as the home of Senator Stephen Douglas , the champion of the Kansas–Nebraska Act and the "popular sovereignty" approach to the issue of the spread of slavery. These issues also helped propel another Illinoisan, Abraham Lincoln , to the national stage. Lincoln was nominated in Chicago for U.S. president at the 1860 Republican National Convention , which was held in a purpose-built auditorium called the Wigwam . He defeated Douglas in the general election, and this set the stage for the American Civil War . To accommodate rapid population growth and demand for better sanitation, the city improved its infrastructure. In February 1856, Chicago's Common Council approved Chesbrough 's plan to build the United States' first comprehensive sewerage system. The project raised much of central Chicago to a new grade with the use of jackscrews for raising buildings. While elevating Chicago, and at first improving the city's health, the untreated sewage and industrial waste now flowed into the Chicago River , and subsequently into Lake Michigan , polluting the city's primary freshwater source. The city responded by tunneling two miles (3.2 km) out into Lake Michigan to newly built water cribs . In 1900, the problem of sewage contamination was largely resolved when the city completed a major engineering feat. It reversed the flow of the Chicago River so that the water flowed away from Lake Michigan rather than into it. This project began with the construction and improvement of the Illinois and Michigan Canal, and was completed with the Chicago Sanitary and Ship Canal that connects to the Illinois River , which flows into the Mississippi River. In 1871, the Great Chicago Fire destroyed an area about 4 miles (6.4 km) long and 1-mile (1.6 km) wide, a large section of the city at the time. Much of the city, including railroads and stockyards , survived intact, and from the ruins of the previous wooden structures arose more modern constructions of steel and stone. These set a precedent for worldwide construction. During its rebuilding period, Chicago constructed the world's first skyscraper in 1885, using steel-skeleton construction. The city grew significantly in size and population by incorporating many neighboring townships between 1851 and 1920, with the largest annexation happening in 1889, with five townships joining the city, including the Hyde Park Township , which now comprises most of the South Side of Chicago and the far southeast of Chicago, and the Jefferson Township , which now makes up most of Chicago's Northwest Side . The desire to join the city was driven by municipal services that the city could provide its residents. Chicago's flourishing economy attracted huge numbers of new immigrants from Europe and migrants from the Eastern United States . Of the total population in 1900, more than 77% were either foreign-born or born in the United States of foreign parentage. Germans , Irish , Poles , Swedes , and Czechs made up nearly two-thirds of the foreign-born population (by 1900, whites were 98.1% of the city's population). Labor conflicts followed the industrial boom and the rapid expansion of the labor pool, including the Haymarket affair on May 4, 1886, and in 1894 the Pullman Strike . Anarchist and socialist groups played prominent roles in creating very large and highly organized labor actions. Concern for social problems among Chicago's immigrant poor led Jane Addams and Ellen Gates Starr to found Hull House in 1889. Programs that were developed there became a model for the new field of social work . During the 1870s and 1880s, Chicago attained national stature as the leader in the movement to improve public health. City laws and later, state laws that upgraded standards for the medical profession and fought urban epidemics of cholera , smallpox , and yellow fever were both passed and enforced. These laws became templates for public health reform in other cities and states. The city established many large, well-landscaped municipal parks , which also included public sanitation facilities. The chief advocate for improving public health in Chicago was John H. Rauch, M.D. Rauch established a plan for Chicago's park system in 1866. He created Lincoln Park by closing a cemetery filled with shallow graves, and in 1867, in response to an outbreak of cholera he helped establish a new Chicago Board of Health. Ten years later, he became the secretary and then the president of the first Illinois State Board of Health, which carried out most of its activities in Chicago. In the 1800s, Chicago became the nation's railroad hub, and by 1910 over 20 railroads operated passenger service out of six different downtown terminals. In 1883, Chicago's railway managers needed a general time convention, so they developed the standardized system of North American time zones . This system for telling time spread throughout the continent. In 1893, Chicago hosted the World's Columbian Exposition on former marshland at the present location of Jackson Park . The Exposition drew 27.5 million visitors, and is considered the most influential world's fair in history. The University of Chicago , formerly at another location, moved to the same South Side location in 1892. The term "midway" for a fair or carnival referred originally to the Midway Plaisance , a strip of park land that still runs through the University of Chicago campus and connects the Washington and Jackson Parks. During World War I and the 1920s there was a major expansion in industry. The availability of jobs attracted African Americans from the Southern United States . Between 1910 and 1930, the African American population of Chicago increased dramatically, from 44,103 to 233,903. This Great Migration had an immense cultural impact, called the Chicago Black Renaissance , part of the New Negro Movement , in art, literature, and music. Continuing racial tensions and violence, such as the Chicago race riot of 1919 , also occurred. The ratification of the 18th amendment to the Constitution in 1919 made the production and sale (including exportation) of alcoholic beverages illegal in the United States. This ushered in the beginning of what is known as the gangster era, a time that roughly spans from 1919 until 1933 when Prohibition was repealed. The 1920s saw gangsters , including Al Capone , Dion O'Banion , Bugs Moran and Tony Accardo battle law enforcement and each other on the streets of Chicago during the Prohibition era . Chicago was the location of the infamous St. Valentine's Day Massacre in 1929, when Al Capone sent men to gun down members of a rival gang, North Side, led by Bugs Moran. From 1920 to 1921, the city was affected by a series of tenant rent strikes in it. Which lead to the formation of the Chicago Tenants Protective association, passage of the Kessenger tenant laws, and of a heat ordinance that legally required flats to be kept above 68 °F during winter months by landlords. Chicago was the first American city to have a homosexual-rights organization. The organization, formed in 1924, was called the Society for Human Rights . It produced the first American publication for homosexuals, Friendship and Freedom . Police and political pressure caused the organization to disband. The Great Depression brought unprecedented suffering to Chicago, in no small part due to the city's heavy reliance on heavy industry. Notably, industrial areas on the south side and neighborhoods lining both branches of the Chicago River were devastated; by 1933 over 50% of industrial jobs in the city had been lost, and unemployment rates amongst blacks and Mexicans in the city were over 40%. The Republican political machine in Chicago was utterly destroyed by the economic crisis, and every mayor since 1931 has been a Democrat . From 1928 to 1933, the city witnessed a tax revolt, and the city was unable to meet payroll or provide relief efforts. The fiscal crisis was resolved by 1933, and at the same time, federal relief funding began to flow into Chicago. Chicago was also a hotbed of labor activism, with Unemployed Councils contributing heavily in the early depression to create solidarity for the poor and demand relief; these organizations were created by socialist and communist groups. By 1935 the Workers Alliance of America begun organizing the poor, workers, the unemployed. In the spring of 1937 Republic Steel Works witnessed the Memorial Day massacre of 1937 in the neighborhood of East Side. In 1933, Chicago Mayor Anton Cermak was fatally wounded in Miami, Florida , during a failed assassination attempt on President-elect Franklin D. Roosevelt . In 1933 and 1934, the city celebrated its centennial by hosting the Century of Progress International Exposition World's Fair . The theme of the fair was technological innovation over the century since Chicago's founding. During World War II , the city of Chicago alone produced more steel than the United Kingdom every year from 1939 – 1945, and more than Nazi Germany from 1943 – 1945. The Great Migration, which had been on pause due to the Depression, resumed at an even faster pace in the second wave , as hundreds of thousands of blacks from the South arrived in the city to work in the steel mills, railroads, and shipping yards. On December 2, 1942, physicist Enrico Fermi conducted the world's first controlled nuclear reaction at the University of Chicago as part of the top-secret Manhattan Project . This led to the creation of the atomic bomb by the United States, which it used in World War II in 1945. Mayor Richard J. Daley , a Democrat, was elected in 1955, in the era of machine politics . In 1956, the city conducted its last major expansion when it annexed the land under O'Hare airport, including a small portion of DuPage County. By the 1960s, white residents in several neighborhoods left the city for the suburban areas – in many American cities, a process known as white flight – as Blacks continued to move beyond the Black Belt . While home loan discriminatory redlining against blacks continued, the real estate industry practiced what became known as blockbusting , completely changing the racial composition of whole neighborhoods. Structural changes in industry, such as globalization and job outsourcing, caused heavy job losses for lower-skilled workers. At its peak during the 1960s, some 250,000 workers were employed in the steel industry in Chicago, but the steel crisis of the 1970s and 1980s reduced this number to just 28,000 in 2015. In 1966, Martin Luther King Jr. and Albert Raby led the Chicago Freedom Movement , which culminated in agreements between Mayor Richard J. Daley and the movement leaders. Two years later, the city hosted the tumultuous 1968 Democratic National Convention , which featured physical confrontations both inside and outside the convention hall, with anti-war protesters, journalists and bystanders being beaten by police. Major construction projects, including the Sears Tower (now known as the Willis Tower , which in 1974 became the world's tallest building ), University of Illinois at Chicago , McCormick Place , and O'Hare International Airport , were undertaken during Richard J. Daley's tenure. In 1979, Jane Byrne , the city's first female mayor, was elected. She was notable for temporarily moving into the crime-ridden Cabrini-Green housing project and for leading Chicago's school system out of a financial crisis. In 1983, Harold Washington became the first black mayor of Chicago. Washington's first term in office directed attention to poor and previously neglected minority neighborhoods. He was re‑elected in 1987 but died of a heart attack soon after. Washington was succeeded by 6th ward alderperson Eugene Sawyer , who was elected by the Chicago City Council and served until a special election. Richard M. Daley , son of Richard J. Daley, was elected in 1989. His accomplishments included improvements to parks and creating incentives for sustainable development , as well as closing Meigs Field in the middle of the night and destroying the runways. After successfully running for re-election five times, and becoming Chicago's longest-serving mayor, Richard M. Daley declined to run for a seventh term. In 1992, a construction accident near the Kinzie Street Bridge produced a breach connecting the Chicago River to a tunnel below, which was part of an abandoned freight tunnel system extending throughout the downtown Loop district. The tunnels filled with 250 million US gallons (1,000,000 m 3 ) of water, affecting buildings throughout the district and forcing a shutdown of electrical power. The area was shut down for three days and some buildings did not reopen for weeks; losses were estimated at $1.95 billion. On February 23, 2011, Rahm Emanuel , a former White House Chief of Staff and member of the House of Representatives , won the mayoral election. Emanuel was sworn in as mayor on May 16, 2011, and won re-election in 2015. Lori Lightfoot , the city's first African American woman mayor and its first openly LGBTQ mayor, was elected to succeed Emanuel as mayor in 2019. All three city-wide elective offices were held by women (and women of color) for the first time in Chicago history: in addition to Lightfoot, the city clerk was Anna Valencia and the city treasurer was Melissa Conyears-Ervin . On May 15, 2023, Brandon Johnson assumed office as the 57th mayor of Chicago.In the mid-18th century, the area was inhabited by the Potawatomi , an indigenous tribe who had succeeded the Miami and Sauk and Fox peoples in this region. The first known permanent settler in Chicago was trader Jean Baptiste Point du Sable . Du Sable was of African descent, perhaps born in the French colony of Saint-Domingue (Haiti), and established the settlement in the 1780s. He is commonly known as the "Founder of Chicago". In 1795, following the victory of the new United States in the Northwest Indian War , an area that was to be part of Chicago was turned over to the U.S. for a military post by native tribes in accordance with the Treaty of Greenville . In 1803, the U.S. Army constructed Fort Dearborn , which was destroyed during the War of 1812 in the Battle of Fort Dearborn by the Potawatomi before being later rebuilt. After the War of 1812, the Ottawa , Ojibwe , and Potawatomi tribes ceded additional land to the United States in the 1816 Treaty of St. Louis . The Potawatomi were forcibly removed from their land after the 1833 Treaty of Chicago and sent west of the Mississippi River as part of the federal policy of Indian removal . On August 12, 1833, the Town of Chicago was organized with a population of about 200. Within seven years it grew to more than 6,000 people. On June 15, 1835, the first public land sales began with Edmund Dick Taylor as Receiver of Public Monies. The City of Chicago was incorporated on Saturday, March 4, 1837, and for several decades was the world's fastest-growing city. As the site of the Chicago Portage , the city became an important transportation hub between the eastern and western United States. Chicago's first railway, Galena and Chicago Union Railroad , and the Illinois and Michigan Canal opened in 1848. The canal allowed steamboats and sailing ships on the Great Lakes to connect to the Mississippi River. A flourishing economy brought residents from rural communities and immigrants from abroad. Manufacturing and retail and finance sectors became dominant, influencing the American economy . The Chicago Board of Trade (established 1848) listed the first-ever standardized "exchange-traded" forward contracts, which were called futures contracts . In the 1850s, Chicago gained national political prominence as the home of Senator Stephen Douglas , the champion of the Kansas–Nebraska Act and the "popular sovereignty" approach to the issue of the spread of slavery. These issues also helped propel another Illinoisan, Abraham Lincoln , to the national stage. Lincoln was nominated in Chicago for U.S. president at the 1860 Republican National Convention , which was held in a purpose-built auditorium called the Wigwam . He defeated Douglas in the general election, and this set the stage for the American Civil War . To accommodate rapid population growth and demand for better sanitation, the city improved its infrastructure. In February 1856, Chicago's Common Council approved Chesbrough 's plan to build the United States' first comprehensive sewerage system. The project raised much of central Chicago to a new grade with the use of jackscrews for raising buildings. While elevating Chicago, and at first improving the city's health, the untreated sewage and industrial waste now flowed into the Chicago River , and subsequently into Lake Michigan , polluting the city's primary freshwater source. The city responded by tunneling two miles (3.2 km) out into Lake Michigan to newly built water cribs . In 1900, the problem of sewage contamination was largely resolved when the city completed a major engineering feat. It reversed the flow of the Chicago River so that the water flowed away from Lake Michigan rather than into it. This project began with the construction and improvement of the Illinois and Michigan Canal, and was completed with the Chicago Sanitary and Ship Canal that connects to the Illinois River , which flows into the Mississippi River. In 1871, the Great Chicago Fire destroyed an area about 4 miles (6.4 km) long and 1-mile (1.6 km) wide, a large section of the city at the time. Much of the city, including railroads and stockyards , survived intact, and from the ruins of the previous wooden structures arose more modern constructions of steel and stone. These set a precedent for worldwide construction. During its rebuilding period, Chicago constructed the world's first skyscraper in 1885, using steel-skeleton construction. The city grew significantly in size and population by incorporating many neighboring townships between 1851 and 1920, with the largest annexation happening in 1889, with five townships joining the city, including the Hyde Park Township , which now comprises most of the South Side of Chicago and the far southeast of Chicago, and the Jefferson Township , which now makes up most of Chicago's Northwest Side . The desire to join the city was driven by municipal services that the city could provide its residents. Chicago's flourishing economy attracted huge numbers of new immigrants from Europe and migrants from the Eastern United States . Of the total population in 1900, more than 77% were either foreign-born or born in the United States of foreign parentage. Germans , Irish , Poles , Swedes , and Czechs made up nearly two-thirds of the foreign-born population (by 1900, whites were 98.1% of the city's population). Labor conflicts followed the industrial boom and the rapid expansion of the labor pool, including the Haymarket affair on May 4, 1886, and in 1894 the Pullman Strike . Anarchist and socialist groups played prominent roles in creating very large and highly organized labor actions. Concern for social problems among Chicago's immigrant poor led Jane Addams and Ellen Gates Starr to found Hull House in 1889. Programs that were developed there became a model for the new field of social work . During the 1870s and 1880s, Chicago attained national stature as the leader in the movement to improve public health. City laws and later, state laws that upgraded standards for the medical profession and fought urban epidemics of cholera , smallpox , and yellow fever were both passed and enforced. These laws became templates for public health reform in other cities and states. The city established many large, well-landscaped municipal parks , which also included public sanitation facilities. The chief advocate for improving public health in Chicago was John H. Rauch, M.D. Rauch established a plan for Chicago's park system in 1866. He created Lincoln Park by closing a cemetery filled with shallow graves, and in 1867, in response to an outbreak of cholera he helped establish a new Chicago Board of Health. Ten years later, he became the secretary and then the president of the first Illinois State Board of Health, which carried out most of its activities in Chicago. In the 1800s, Chicago became the nation's railroad hub, and by 1910 over 20 railroads operated passenger service out of six different downtown terminals. In 1883, Chicago's railway managers needed a general time convention, so they developed the standardized system of North American time zones . This system for telling time spread throughout the continent. In 1893, Chicago hosted the World's Columbian Exposition on former marshland at the present location of Jackson Park . The Exposition drew 27.5 million visitors, and is considered the most influential world's fair in history. The University of Chicago , formerly at another location, moved to the same South Side location in 1892. The term "midway" for a fair or carnival referred originally to the Midway Plaisance , a strip of park land that still runs through the University of Chicago campus and connects the Washington and Jackson Parks. During World War I and the 1920s there was a major expansion in industry. The availability of jobs attracted African Americans from the Southern United States . Between 1910 and 1930, the African American population of Chicago increased dramatically, from 44,103 to 233,903. This Great Migration had an immense cultural impact, called the Chicago Black Renaissance , part of the New Negro Movement , in art, literature, and music. Continuing racial tensions and violence, such as the Chicago race riot of 1919 , also occurred. The ratification of the 18th amendment to the Constitution in 1919 made the production and sale (including exportation) of alcoholic beverages illegal in the United States. This ushered in the beginning of what is known as the gangster era, a time that roughly spans from 1919 until 1933 when Prohibition was repealed. The 1920s saw gangsters , including Al Capone , Dion O'Banion , Bugs Moran and Tony Accardo battle law enforcement and each other on the streets of Chicago during the Prohibition era . Chicago was the location of the infamous St. Valentine's Day Massacre in 1929, when Al Capone sent men to gun down members of a rival gang, North Side, led by Bugs Moran. From 1920 to 1921, the city was affected by a series of tenant rent strikes in it. Which lead to the formation of the Chicago Tenants Protective association, passage of the Kessenger tenant laws, and of a heat ordinance that legally required flats to be kept above 68 °F during winter months by landlords. Chicago was the first American city to have a homosexual-rights organization. The organization, formed in 1924, was called the Society for Human Rights . It produced the first American publication for homosexuals, Friendship and Freedom . Police and political pressure caused the organization to disband. The Great Depression brought unprecedented suffering to Chicago, in no small part due to the city's heavy reliance on heavy industry. Notably, industrial areas on the south side and neighborhoods lining both branches of the Chicago River were devastated; by 1933 over 50% of industrial jobs in the city had been lost, and unemployment rates amongst blacks and Mexicans in the city were over 40%. The Republican political machine in Chicago was utterly destroyed by the economic crisis, and every mayor since 1931 has been a Democrat . From 1928 to 1933, the city witnessed a tax revolt, and the city was unable to meet payroll or provide relief efforts. The fiscal crisis was resolved by 1933, and at the same time, federal relief funding began to flow into Chicago. Chicago was also a hotbed of labor activism, with Unemployed Councils contributing heavily in the early depression to create solidarity for the poor and demand relief; these organizations were created by socialist and communist groups. By 1935 the Workers Alliance of America begun organizing the poor, workers, the unemployed. In the spring of 1937 Republic Steel Works witnessed the Memorial Day massacre of 1937 in the neighborhood of East Side. In 1933, Chicago Mayor Anton Cermak was fatally wounded in Miami, Florida , during a failed assassination attempt on President-elect Franklin D. Roosevelt . In 1933 and 1934, the city celebrated its centennial by hosting the Century of Progress International Exposition World's Fair . The theme of the fair was technological innovation over the century since Chicago's founding. During World War II , the city of Chicago alone produced more steel than the United Kingdom every year from 1939 – 1945, and more than Nazi Germany from 1943 – 1945. The Great Migration, which had been on pause due to the Depression, resumed at an even faster pace in the second wave , as hundreds of thousands of blacks from the South arrived in the city to work in the steel mills, railroads, and shipping yards. On December 2, 1942, physicist Enrico Fermi conducted the world's first controlled nuclear reaction at the University of Chicago as part of the top-secret Manhattan Project . This led to the creation of the atomic bomb by the United States, which it used in World War II in 1945. Mayor Richard J. Daley , a Democrat, was elected in 1955, in the era of machine politics . In 1956, the city conducted its last major expansion when it annexed the land under O'Hare airport, including a small portion of DuPage County. By the 1960s, white residents in several neighborhoods left the city for the suburban areas – in many American cities, a process known as white flight – as Blacks continued to move beyond the Black Belt . While home loan discriminatory redlining against blacks continued, the real estate industry practiced what became known as blockbusting , completely changing the racial composition of whole neighborhoods. Structural changes in industry, such as globalization and job outsourcing, caused heavy job losses for lower-skilled workers. At its peak during the 1960s, some 250,000 workers were employed in the steel industry in Chicago, but the steel crisis of the 1970s and 1980s reduced this number to just 28,000 in 2015. In 1966, Martin Luther King Jr. and Albert Raby led the Chicago Freedom Movement , which culminated in agreements between Mayor Richard J. Daley and the movement leaders. Two years later, the city hosted the tumultuous 1968 Democratic National Convention , which featured physical confrontations both inside and outside the convention hall, with anti-war protesters, journalists and bystanders being beaten by police. Major construction projects, including the Sears Tower (now known as the Willis Tower , which in 1974 became the world's tallest building ), University of Illinois at Chicago , McCormick Place , and O'Hare International Airport , were undertaken during Richard J. Daley's tenure. In 1979, Jane Byrne , the city's first female mayor, was elected. She was notable for temporarily moving into the crime-ridden Cabrini-Green housing project and for leading Chicago's school system out of a financial crisis. In 1983, Harold Washington became the first black mayor of Chicago. Washington's first term in office directed attention to poor and previously neglected minority neighborhoods. He was re‑elected in 1987 but died of a heart attack soon after. Washington was succeeded by 6th ward alderperson Eugene Sawyer , who was elected by the Chicago City Council and served until a special election. Richard M. Daley , son of Richard J. Daley, was elected in 1989. His accomplishments included improvements to parks and creating incentives for sustainable development , as well as closing Meigs Field in the middle of the night and destroying the runways. After successfully running for re-election five times, and becoming Chicago's longest-serving mayor, Richard M. Daley declined to run for a seventh term. In 1992, a construction accident near the Kinzie Street Bridge produced a breach connecting the Chicago River to a tunnel below, which was part of an abandoned freight tunnel system extending throughout the downtown Loop district. The tunnels filled with 250 million US gallons (1,000,000 m 3 ) of water, affecting buildings throughout the district and forcing a shutdown of electrical power. The area was shut down for three days and some buildings did not reopen for weeks; losses were estimated at $1.95 billion. On February 23, 2011, Rahm Emanuel , a former White House Chief of Staff and member of the House of Representatives , won the mayoral election. Emanuel was sworn in as mayor on May 16, 2011, and won re-election in 2015. Lori Lightfoot , the city's first African American woman mayor and its first openly LGBTQ mayor, was elected to succeed Emanuel as mayor in 2019. All three city-wide elective offices were held by women (and women of color) for the first time in Chicago history: in addition to Lightfoot, the city clerk was Anna Valencia and the city treasurer was Melissa Conyears-Ervin . On May 15, 2023, Brandon Johnson assumed office as the 57th mayor of Chicago.During World War I and the 1920s there was a major expansion in industry. The availability of jobs attracted African Americans from the Southern United States . Between 1910 and 1930, the African American population of Chicago increased dramatically, from 44,103 to 233,903. This Great Migration had an immense cultural impact, called the Chicago Black Renaissance , part of the New Negro Movement , in art, literature, and music. Continuing racial tensions and violence, such as the Chicago race riot of 1919 , also occurred. The ratification of the 18th amendment to the Constitution in 1919 made the production and sale (including exportation) of alcoholic beverages illegal in the United States. This ushered in the beginning of what is known as the gangster era, a time that roughly spans from 1919 until 1933 when Prohibition was repealed. The 1920s saw gangsters , including Al Capone , Dion O'Banion , Bugs Moran and Tony Accardo battle law enforcement and each other on the streets of Chicago during the Prohibition era . Chicago was the location of the infamous St. Valentine's Day Massacre in 1929, when Al Capone sent men to gun down members of a rival gang, North Side, led by Bugs Moran. From 1920 to 1921, the city was affected by a series of tenant rent strikes in it. Which lead to the formation of the Chicago Tenants Protective association, passage of the Kessenger tenant laws, and of a heat ordinance that legally required flats to be kept above 68 °F during winter months by landlords. Chicago was the first American city to have a homosexual-rights organization. The organization, formed in 1924, was called the Society for Human Rights . It produced the first American publication for homosexuals, Friendship and Freedom . Police and political pressure caused the organization to disband. The Great Depression brought unprecedented suffering to Chicago, in no small part due to the city's heavy reliance on heavy industry. Notably, industrial areas on the south side and neighborhoods lining both branches of the Chicago River were devastated; by 1933 over 50% of industrial jobs in the city had been lost, and unemployment rates amongst blacks and Mexicans in the city were over 40%. The Republican political machine in Chicago was utterly destroyed by the economic crisis, and every mayor since 1931 has been a Democrat . From 1928 to 1933, the city witnessed a tax revolt, and the city was unable to meet payroll or provide relief efforts. The fiscal crisis was resolved by 1933, and at the same time, federal relief funding began to flow into Chicago. Chicago was also a hotbed of labor activism, with Unemployed Councils contributing heavily in the early depression to create solidarity for the poor and demand relief; these organizations were created by socialist and communist groups. By 1935 the Workers Alliance of America begun organizing the poor, workers, the unemployed. In the spring of 1937 Republic Steel Works witnessed the Memorial Day massacre of 1937 in the neighborhood of East Side. In 1933, Chicago Mayor Anton Cermak was fatally wounded in Miami, Florida , during a failed assassination attempt on President-elect Franklin D. Roosevelt . In 1933 and 1934, the city celebrated its centennial by hosting the Century of Progress International Exposition World's Fair . The theme of the fair was technological innovation over the century since Chicago's founding. During World War II , the city of Chicago alone produced more steel than the United Kingdom every year from 1939 – 1945, and more than Nazi Germany from 1943 – 1945. The Great Migration, which had been on pause due to the Depression, resumed at an even faster pace in the second wave , as hundreds of thousands of blacks from the South arrived in the city to work in the steel mills, railroads, and shipping yards. On December 2, 1942, physicist Enrico Fermi conducted the world's first controlled nuclear reaction at the University of Chicago as part of the top-secret Manhattan Project . This led to the creation of the atomic bomb by the United States, which it used in World War II in 1945. Mayor Richard J. Daley , a Democrat, was elected in 1955, in the era of machine politics . In 1956, the city conducted its last major expansion when it annexed the land under O'Hare airport, including a small portion of DuPage County. By the 1960s, white residents in several neighborhoods left the city for the suburban areas – in many American cities, a process known as white flight – as Blacks continued to move beyond the Black Belt . While home loan discriminatory redlining against blacks continued, the real estate industry practiced what became known as blockbusting , completely changing the racial composition of whole neighborhoods. Structural changes in industry, such as globalization and job outsourcing, caused heavy job losses for lower-skilled workers. At its peak during the 1960s, some 250,000 workers were employed in the steel industry in Chicago, but the steel crisis of the 1970s and 1980s reduced this number to just 28,000 in 2015. In 1966, Martin Luther King Jr. and Albert Raby led the Chicago Freedom Movement , which culminated in agreements between Mayor Richard J. Daley and the movement leaders. Two years later, the city hosted the tumultuous 1968 Democratic National Convention , which featured physical confrontations both inside and outside the convention hall, with anti-war protesters, journalists and bystanders being beaten by police. Major construction projects, including the Sears Tower (now known as the Willis Tower , which in 1974 became the world's tallest building ), University of Illinois at Chicago , McCormick Place , and O'Hare International Airport , were undertaken during Richard J. Daley's tenure. In 1979, Jane Byrne , the city's first female mayor, was elected. She was notable for temporarily moving into the crime-ridden Cabrini-Green housing project and for leading Chicago's school system out of a financial crisis. In 1983, Harold Washington became the first black mayor of Chicago. Washington's first term in office directed attention to poor and previously neglected minority neighborhoods. He was re‑elected in 1987 but died of a heart attack soon after. Washington was succeeded by 6th ward alderperson Eugene Sawyer , who was elected by the Chicago City Council and served until a special election. Richard M. Daley , son of Richard J. Daley, was elected in 1989. His accomplishments included improvements to parks and creating incentives for sustainable development , as well as closing Meigs Field in the middle of the night and destroying the runways. After successfully running for re-election five times, and becoming Chicago's longest-serving mayor, Richard M. Daley declined to run for a seventh term. In 1992, a construction accident near the Kinzie Street Bridge produced a breach connecting the Chicago River to a tunnel below, which was part of an abandoned freight tunnel system extending throughout the downtown Loop district. The tunnels filled with 250 million US gallons (1,000,000 m 3 ) of water, affecting buildings throughout the district and forcing a shutdown of electrical power. The area was shut down for three days and some buildings did not reopen for weeks; losses were estimated at $1.95 billion. On February 23, 2011, Rahm Emanuel , a former White House Chief of Staff and member of the House of Representatives , won the mayoral election. Emanuel was sworn in as mayor on May 16, 2011, and won re-election in 2015. Lori Lightfoot , the city's first African American woman mayor and its first openly LGBTQ mayor, was elected to succeed Emanuel as mayor in 2019. All three city-wide elective offices were held by women (and women of color) for the first time in Chicago history: in addition to Lightfoot, the city clerk was Anna Valencia and the city treasurer was Melissa Conyears-Ervin . On May 15, 2023, Brandon Johnson assumed office as the 57th mayor of Chicago.Chicago is located in northeastern Illinois on the southwestern shores of freshwater Lake Michigan. It is the principal city in the Chicago metropolitan area , situated in both the Midwestern United States and the Great Lakes region . The city rests on a continental divide at the site of the Chicago Portage, connecting the Mississippi River and the Great Lakes watersheds . In addition to it lying beside Lake Michigan, two rivers—the Chicago River in downtown and the Calumet River in the industrial far South Side—flow either entirely or partially through the city. Chicago's history and economy are closely tied to its proximity to Lake Michigan. While the Chicago River historically handled much of the region's waterborne cargo, today's huge lake freighters use the city's Lake Calumet Harbor on the South Side. The lake also provides another positive effect: moderating Chicago's climate, making waterfront neighborhoods slightly warmer in winter and cooler in summer. When Chicago was founded in 1837, most of the early building was around the mouth of the Chicago River, as can be seen on a map of the city's original 58 blocks. The overall grade of the city's central, built-up areas is relatively consistent with the natural flatness of its overall natural geography, generally exhibiting only slight differentiation otherwise. The average land elevation is 579 ft (176.5 m) above sea level . While measurements vary somewhat, the lowest points are along the lake shore at 578 ft (176.2 m) , while the highest point, at 672 ft (205 m) , is the morainal ridge of Blue Island in the city's far south side. Lake Shore Drive runs adjacent to a large portion of Chicago's waterfront. Some of the parks along the waterfront include Lincoln Park , Grant Park , Burnham Park , and Jackson Park . There are 24 public beaches across 26 miles (42 km) of the waterfront. Landfill extends into portions of the lake providing space for Navy Pier , Northerly Island , the Museum Campus , and large portions of the McCormick Place Convention Center. Most of the city's high-rise commercial and residential buildings are close to the waterfront. An informal name for the entire Chicago metropolitan area is "Chicagoland", which generally means the city and all its suburbs, though different organizations have slightly different definitions. Major sections of the city include the central business district, called the Loop , and the North, South , and West Sides . The three sides of the city are represented on the Flag of Chicago by three horizontal white stripes. The North Side is the most-densely-populated residential section of the city, and many high-rises are located on this side of the city along the lakefront. The South Side is the largest section of the city, encompassing roughly 60% of the city's land area . The South Side contains most of the facilities of the Port of Chicago . In the late-1920s, sociologists at the University of Chicago subdivided the city into 77 distinct community areas , which can further be subdivided into over 200 informally defined neighborhoods . Chicago's streets were laid out in a street grid that grew from the city's original townsite plot, which was bounded by Lake Michigan on the east, North Avenue on the north, Wood Street on the west, and 22nd Street on the south. Streets following the Public Land Survey System section lines later became arterial streets in outlying sections. As new additions to the city were platted, city ordinance required them to be laid out with eight streets to the mile in one direction and sixteen in the other direction, about one street per 200 meters in one direction and one street per 100 meters in the other direction. The grid's regularity provided an efficient means of developing new real estate property. A scattering of diagonal streets, many of them originally Native American trails, also cross the city (Elston, Milwaukee, Ogden, Lincoln, etc.). Many additional diagonal streets were recommended in the Plan of Chicago , but only the extension of Ogden Avenue was ever constructed. In 2016, Chicago was ranked the sixth-most walkable large city in the United States. Many of the city's residential streets have a wide patch of grass or trees between the street and the sidewalk itself. This helps to keep pedestrians on the sidewalk further away from the street traffic. Chicago's Western Avenue is the longest continuous urban street in the world. Other notable streets include Michigan Avenue , State Street , 95th Street , Cicero Avenue , Clark Street , and Belmont Avenue . The City Beautiful movement inspired Chicago's boulevards and parkways. The destruction caused by the Great Chicago Fire led to the largest building boom in the history of the nation. In 1885, the first steel-framed high-rise building , the Home Insurance Building, rose in the city as Chicago ushered in the skyscraper era , which would then be followed by many other cities around the world. Today, Chicago's skyline is among the world's tallest and densest. Some of the United States' tallest towers are located in Chicago; Willis Tower (formerly Sears Tower) is the second tallest building in the Western Hemisphere after One World Trade Center , and Trump International Hotel and Tower is the third tallest in the country. The Loop's historic buildings include the Chicago Board of Trade Building , the Fine Arts Building , 35 East Wacker , and the Chicago Building , 860-880 Lake Shore Drive Apartments by Mies van der Rohe . Many other architects have left their impression on the Chicago skyline such as Daniel Burnham , Louis Sullivan , Charles B. Atwood, John Root, and Helmut Jahn . The Merchandise Mart , once first on the list of largest buildings in the world , currently listed as 44th-largest 2013 as September 9, 2013, had its own zip code until 2008, and stands near the junction of the North and South branches of the Chicago River. Presently, the four tallest buildings in the city are Willis Tower (formerly the Sears Tower, also a building with its own zip code), Trump International Hotel and Tower , the Aon Center (previously the Standard Oil Building), and the John Hancock Center . Industrial districts , such as some areas on the South Side , the areas along the Chicago Sanitary and Ship Canal , and the Northwest Indiana area are clustered. Chicago gave its name to the Chicago School and was home to the Prairie School , two movements in architecture. Multiple kinds and scales of houses, townhouses, condominiums, and apartment buildings can be found throughout Chicago. Large swaths of the city's residential areas away from the lake are characterized by brick bungalows built from the early 20th century through the end of World War II. Chicago is also a prominent center of the Polish Cathedral style of church architecture . The Chicago suburb of Oak Park was home to famous architect Frank Lloyd Wright , who had designed The Robie House located near the University of Chicago. A popular tourist activity is to take an architecture boat tour along the Chicago River. Chicago is famous for its outdoor public art with donors establishing funding for such art as far back as Benjamin Ferguson 's 1905 trust. A number of Chicago's public art works are by modern figurative artists. Among these are Chagall's Four Seasons ; the Chicago Picasso ; Miro's Chicago ; Calder's Flamingo ; Oldenburg's Batcolumn ; Moore's Large Interior Form, 1953-54 , Man Enters the Cosmos and Nuclear Energy ; Dubuffet's Monument with Standing Beast , Abakanowicz's Agora ; and, Anish Kapoor 's Cloud Gate which has become an icon of the city. Some events which shaped the city's history have also been memorialized by art works, including the Great Northern Migration ( Saar ) and the centennial of statehood for Illinois . Finally, two fountains near the Loop also function as monumental works of art: Plensa's Crown Fountain as well as Burnham and Bennett's Buckingham Fountain . The city lies within the typical hot-summer humid continental climate ( Köppen : Dfa ), and experiences four distinct seasons. Summers are hot and humid, with frequent heat waves . The July daily average temperature is 75.4 °F (24.1 °C) , with afternoon temperatures peaking at 84.5 °F (29.2 °C) . In a normal summer, temperatures reach at least 90 °F (32 °C) on 17 days, with lakefront locations staying cooler when winds blow off the lake. Winters are relatively cold and snowy. Blizzards do occur, such as in winter 2011 . There are many sunny but cold days. The normal winter high from December through March is about 36 °F (2 °C) . January and February are the coldest months. A polar vortex in January 2019 nearly broke the city's cold record of −27 °F (−33 °C) , which was set on January 20, 1985. Measurable snowfall can continue through the first or second week of April. Spring and autumn are mild, short seasons, typically with low humidity. Dew point temperatures in the summer range from an average of 55.8 °F (13.2 °C) in June to 61.7 °F (16.5 °C) in July. They can reach nearly 80 °F (27 °C) , such as during the July 2019 heat wave. The city lies within USDA plant hardiness zone 6a, transitioning to 5b in the suburbs. According to the National Weather Service , Chicago's highest official temperature reading of 105 °F (41 °C) was recorded on July 24, 1934. Midway Airport reached 109 °F (43 °C) one day prior and recorded a heat index of 125 °F (52 °C) during the 1995 heatwave . The lowest official temperature of −27 °F (−33 °C) was recorded on January 20, 1985 , at O'Hare Airport. Most of the city's rainfall is brought by thunderstorms , averaging 38 a year. The region is prone to severe thunderstorms during the spring and summer which can produce large hail, damaging winds, and occasionally tornadoes. Like other major cities, Chicago experiences an urban heat island , making the city and its suburbs milder than surrounding rural areas, especially at night and in winter. The proximity to Lake Michigan tends to keep the Chicago lakefront somewhat cooler in summer and less brutally cold in winter than inland parts of the city and suburbs away from the lake. Northeast winds from wintertime cyclones departing south of the region sometimes bring the city lake-effect snow . As in the rest of the state of Illinois, Chicago forms part of the Central Time Zone . The border with the Eastern Time Zone is located a short distance to the east, used in Michigan and certain parts of Indiana .Chicago is located in northeastern Illinois on the southwestern shores of freshwater Lake Michigan. It is the principal city in the Chicago metropolitan area , situated in both the Midwestern United States and the Great Lakes region . The city rests on a continental divide at the site of the Chicago Portage, connecting the Mississippi River and the Great Lakes watersheds . In addition to it lying beside Lake Michigan, two rivers—the Chicago River in downtown and the Calumet River in the industrial far South Side—flow either entirely or partially through the city. Chicago's history and economy are closely tied to its proximity to Lake Michigan. While the Chicago River historically handled much of the region's waterborne cargo, today's huge lake freighters use the city's Lake Calumet Harbor on the South Side. The lake also provides another positive effect: moderating Chicago's climate, making waterfront neighborhoods slightly warmer in winter and cooler in summer. When Chicago was founded in 1837, most of the early building was around the mouth of the Chicago River, as can be seen on a map of the city's original 58 blocks. The overall grade of the city's central, built-up areas is relatively consistent with the natural flatness of its overall natural geography, generally exhibiting only slight differentiation otherwise. The average land elevation is 579 ft (176.5 m) above sea level . While measurements vary somewhat, the lowest points are along the lake shore at 578 ft (176.2 m) , while the highest point, at 672 ft (205 m) , is the morainal ridge of Blue Island in the city's far south side. Lake Shore Drive runs adjacent to a large portion of Chicago's waterfront. Some of the parks along the waterfront include Lincoln Park , Grant Park , Burnham Park , and Jackson Park . There are 24 public beaches across 26 miles (42 km) of the waterfront. Landfill extends into portions of the lake providing space for Navy Pier , Northerly Island , the Museum Campus , and large portions of the McCormick Place Convention Center. Most of the city's high-rise commercial and residential buildings are close to the waterfront. An informal name for the entire Chicago metropolitan area is "Chicagoland", which generally means the city and all its suburbs, though different organizations have slightly different definitions. Major sections of the city include the central business district, called the Loop , and the North, South , and West Sides . The three sides of the city are represented on the Flag of Chicago by three horizontal white stripes. The North Side is the most-densely-populated residential section of the city, and many high-rises are located on this side of the city along the lakefront. The South Side is the largest section of the city, encompassing roughly 60% of the city's land area . The South Side contains most of the facilities of the Port of Chicago . In the late-1920s, sociologists at the University of Chicago subdivided the city into 77 distinct community areas , which can further be subdivided into over 200 informally defined neighborhoods . Chicago's streets were laid out in a street grid that grew from the city's original townsite plot, which was bounded by Lake Michigan on the east, North Avenue on the north, Wood Street on the west, and 22nd Street on the south. Streets following the Public Land Survey System section lines later became arterial streets in outlying sections. As new additions to the city were platted, city ordinance required them to be laid out with eight streets to the mile in one direction and sixteen in the other direction, about one street per 200 meters in one direction and one street per 100 meters in the other direction. The grid's regularity provided an efficient means of developing new real estate property. A scattering of diagonal streets, many of them originally Native American trails, also cross the city (Elston, Milwaukee, Ogden, Lincoln, etc.). Many additional diagonal streets were recommended in the Plan of Chicago , but only the extension of Ogden Avenue was ever constructed. In 2016, Chicago was ranked the sixth-most walkable large city in the United States. Many of the city's residential streets have a wide patch of grass or trees between the street and the sidewalk itself. This helps to keep pedestrians on the sidewalk further away from the street traffic. Chicago's Western Avenue is the longest continuous urban street in the world. Other notable streets include Michigan Avenue , State Street , 95th Street , Cicero Avenue , Clark Street , and Belmont Avenue . The City Beautiful movement inspired Chicago's boulevards and parkways. The destruction caused by the Great Chicago Fire led to the largest building boom in the history of the nation. In 1885, the first steel-framed high-rise building , the Home Insurance Building, rose in the city as Chicago ushered in the skyscraper era , which would then be followed by many other cities around the world. Today, Chicago's skyline is among the world's tallest and densest. Some of the United States' tallest towers are located in Chicago; Willis Tower (formerly Sears Tower) is the second tallest building in the Western Hemisphere after One World Trade Center , and Trump International Hotel and Tower is the third tallest in the country. The Loop's historic buildings include the Chicago Board of Trade Building , the Fine Arts Building , 35 East Wacker , and the Chicago Building , 860-880 Lake Shore Drive Apartments by Mies van der Rohe . Many other architects have left their impression on the Chicago skyline such as Daniel Burnham , Louis Sullivan , Charles B. Atwood, John Root, and Helmut Jahn . The Merchandise Mart , once first on the list of largest buildings in the world , currently listed as 44th-largest 2013 as September 9, 2013, had its own zip code until 2008, and stands near the junction of the North and South branches of the Chicago River. Presently, the four tallest buildings in the city are Willis Tower (formerly the Sears Tower, also a building with its own zip code), Trump International Hotel and Tower , the Aon Center (previously the Standard Oil Building), and the John Hancock Center . Industrial districts , such as some areas on the South Side , the areas along the Chicago Sanitary and Ship Canal , and the Northwest Indiana area are clustered. Chicago gave its name to the Chicago School and was home to the Prairie School , two movements in architecture. Multiple kinds and scales of houses, townhouses, condominiums, and apartment buildings can be found throughout Chicago. Large swaths of the city's residential areas away from the lake are characterized by brick bungalows built from the early 20th century through the end of World War II. Chicago is also a prominent center of the Polish Cathedral style of church architecture . The Chicago suburb of Oak Park was home to famous architect Frank Lloyd Wright , who had designed The Robie House located near the University of Chicago. A popular tourist activity is to take an architecture boat tour along the Chicago River. Chicago is famous for its outdoor public art with donors establishing funding for such art as far back as Benjamin Ferguson 's 1905 trust. A number of Chicago's public art works are by modern figurative artists. Among these are Chagall's Four Seasons ; the Chicago Picasso ; Miro's Chicago ; Calder's Flamingo ; Oldenburg's Batcolumn ; Moore's Large Interior Form, 1953-54 , Man Enters the Cosmos and Nuclear Energy ; Dubuffet's Monument with Standing Beast , Abakanowicz's Agora ; and, Anish Kapoor 's Cloud Gate which has become an icon of the city. Some events which shaped the city's history have also been memorialized by art works, including the Great Northern Migration ( Saar ) and the centennial of statehood for Illinois . Finally, two fountains near the Loop also function as monumental works of art: Plensa's Crown Fountain as well as Burnham and Bennett's Buckingham Fountain . The city lies within the typical hot-summer humid continental climate ( Köppen : Dfa ), and experiences four distinct seasons. Summers are hot and humid, with frequent heat waves . The July daily average temperature is 75.4 °F (24.1 °C) , with afternoon temperatures peaking at 84.5 °F (29.2 °C) . In a normal summer, temperatures reach at least 90 °F (32 °C) on 17 days, with lakefront locations staying cooler when winds blow off the lake. Winters are relatively cold and snowy. Blizzards do occur, such as in winter 2011 . There are many sunny but cold days. The normal winter high from December through March is about 36 °F (2 °C) . January and February are the coldest months. A polar vortex in January 2019 nearly broke the city's cold record of −27 °F (−33 °C) , which was set on January 20, 1985. Measurable snowfall can continue through the first or second week of April. Spring and autumn are mild, short seasons, typically with low humidity. Dew point temperatures in the summer range from an average of 55.8 °F (13.2 °C) in June to 61.7 °F (16.5 °C) in July. They can reach nearly 80 °F (27 °C) , such as during the July 2019 heat wave. The city lies within USDA plant hardiness zone 6a, transitioning to 5b in the suburbs. According to the National Weather Service , Chicago's highest official temperature reading of 105 °F (41 °C) was recorded on July 24, 1934. Midway Airport reached 109 °F (43 °C) one day prior and recorded a heat index of 125 °F (52 °C) during the 1995 heatwave . The lowest official temperature of −27 °F (−33 °C) was recorded on January 20, 1985 , at O'Hare Airport. Most of the city's rainfall is brought by thunderstorms , averaging 38 a year. The region is prone to severe thunderstorms during the spring and summer which can produce large hail, damaging winds, and occasionally tornadoes. Like other major cities, Chicago experiences an urban heat island , making the city and its suburbs milder than surrounding rural areas, especially at night and in winter. The proximity to Lake Michigan tends to keep the Chicago lakefront somewhat cooler in summer and less brutally cold in winter than inland parts of the city and suburbs away from the lake. Northeast winds from wintertime cyclones departing south of the region sometimes bring the city lake-effect snow . As in the rest of the state of Illinois, Chicago forms part of the Central Time Zone . The border with the Eastern Time Zone is located a short distance to the east, used in Michigan and certain parts of Indiana .During its first hundred years, Chicago was one of the fastest-growing cities in the world. When founded in 1833, fewer than 200 people had settled on what was then the American frontier. By the time of its first census, seven years later, the population had reached over 4,000. In the forty years from 1850 to 1890, the city's population grew from slightly under 30,000 to over 1 million. At the end of the 19th century, Chicago was the fifth-largest city in the world, and the largest of the cities that did not exist at the dawn of the century. Within sixty years of the Great Chicago Fire of 1871, the population went from about 300,000 to over 3 million, and reached its highest ever recorded population of 3.6 million for the 1950 census. From the last two decades of the 19th century, Chicago was the destination of waves of immigrants from Ireland, Southern, Central and Eastern Europe, including Italians , Jews , Russians , Poles , Greeks , Lithuanians , Bulgarians , Albanians , Romanians , Turkish , Croatians , Serbs , Bosnians , Montenegrins and Czechs . To these ethnic groups, the basis of the city's industrial working class , were added an additional influx of African Americans from the American South —with Chicago's black population doubling between 1910 and 1920 and doubling again between 1920 and 1930. Chicago has a significant Bosnian population , many of whom arrived in the 1990s and 2000s. In the 1920s and 1930s, the great majority of African Americans moving to Chicago settled in a so‑called " Black Belt " on the city's South Side . A large number of blacks also settled on the West Side . By 1930, two-thirds of Chicago's black population lived in sections of the city which were 90% black in racial composition. Around that time, a lesser known fact about African Americans on the North Side is that the block of 4600 Winthrop Avenue in Uptown was the only block African Americans could live or open establishments. Chicago's South Side emerged as United States second-largest urban black concentration, following New York's Harlem . In 1990, Chicago's South Side and the adjoining south suburbs constituted the largest black majority region in the entire United States. Since the 1980s, Chicago has had a massive exodus of African Americans (primarily from the South and West sides) to its suburbs or outside its metropolitan area. The above average crime and cost of living were leading reasons for the fast declining African American population in Chicago. Most of Chicago's foreign-born population were born in Mexico , Poland and India . Chicago's population declined in the latter half of the 20th century, from over 3.6 million in 1950 down to under 2.7 million by 2010. By the time of the official census count in 1990, it was overtaken by Los Angeles as the United States' second largest city. The city has seen a rise in population for the 2000 census and after a decrease in 2010, it rose again for the 2020 census. According to U.S. census estimates as of July 2019 [ update ] , Chicago's largest racial or ethnic group is non-Hispanic White at 32.8% of the population, Blacks at 30.1% and the Hispanic population at 29.0% of the population. Chicago has the third-largest LGBT population in the United States. In 2018, the Chicago Department of Health, estimated 7.5% of the adult population, approximately 146,000 Chicagoans, were LGBTQ. In 2015, roughly 4% of the population identified as LGBT. Since the 2013 legalization of same-sex marriage in Illinois , over 10,000 same-sex couples have wed in Cook County , a majority of them in Chicago. Chicago became a "de jure" sanctuary city in 2012 when Mayor Rahm Emanuel and the City Council passed the Welcoming City Ordinance. According to the U.S. Census Bureau's American Community Survey data estimates for 2008–2012, the median income for a household in the city was $47,408, and the median income for a family was $54,188. Male full-time workers had a median income of $47,074 versus $42,063 for females. About 18.3% of families and 22.1% of the population lived below the poverty line. In 2018, Chicago ranked seventh globally for the highest number of ultra-high-net-worth residents with roughly 3,300 residents worth more than $30 million. According to the 2008–2012 American Community Survey, the ancestral groups having 10,000 or more persons in Chicago were: Ireland (137,799) Poland (134,032) Germany (120,328) Italy (77,967) China (66,978) American (37,118) UK (36,145) recent African (32,727) India (25,000) Russia (19,771) Arab (17,598) European (15,753) Sweden (15,151) Japan (15,142) Greece (15,129) France (except Basque) (11,410) Ukraine (11,104) West Indian (except Hispanic groups) (10,349) Persons identifying themselves in "Other groups" were classified at 1.72 million, and unclassified or not reported were approximately 153,000. Religion in Chicago (2014) According to a 2014 study by the Pew Research Center , Christianity is the most prevalently practiced religion in Chicago (71%), with the city being the fourth-most religious metropolis in the United States after Dallas , Atlanta and Houston . Roman Catholicism and Protestantism are the largest branches (34% and 35% respectively), followed by Eastern Orthodoxy and Jehovah's Witnesses with 1% each. Chicago also has a sizable non-Christian population. Non-Christian groups include Irreligious (22%), Judaism (3%), Islam (2%), Buddhism (1%) and Hinduism (1%). Chicago is the headquarters of several religious denominations, including the Evangelical Covenant Church and the Evangelical Lutheran Church in America . It is the seat of several dioceses . The Fourth Presbyterian Church is one of the largest Presbyterian congregations in the United States based on memberships. Since the 20th century Chicago has also been the headquarters of the Assyrian Church of the East . In 2014 the Catholic Church was the largest individual Christian denomination (34%), with the Roman Catholic Archdiocese of Chicago being the largest Catholic jurisdiction. Evangelical Protestantism form the largest theological Protestant branch (16%), followed by Mainline Protestants (11%), and historically Black churches (8%). Among denominational Protestant branches, Baptists formed the largest group in Chicago (10%); followed by Nondenominational (5%); Lutherans (4%); and Pentecostals (3%). Non-Christian faiths accounted for 7% of the religious population in 2014. Judaism has at least 261,000 adherents which is 3% of the population, making it the second largest religion. A 2020 study estimated the total Jewish population of the Chicago metropolitan area, both religious and irreligious, at 319,500. The first two Parliament of the World's Religions in 1893 and 1993 were held in Chicago. Many international religious leaders have visited Chicago, including Mother Teresa , the Dalai Lama and Pope John Paul II in 1979. Religion in Chicago (2014) According to a 2014 study by the Pew Research Center , Christianity is the most prevalently practiced religion in Chicago (71%), with the city being the fourth-most religious metropolis in the United States after Dallas , Atlanta and Houston . Roman Catholicism and Protestantism are the largest branches (34% and 35% respectively), followed by Eastern Orthodoxy and Jehovah's Witnesses with 1% each. Chicago also has a sizable non-Christian population. Non-Christian groups include Irreligious (22%), Judaism (3%), Islam (2%), Buddhism (1%) and Hinduism (1%). Chicago is the headquarters of several religious denominations, including the Evangelical Covenant Church and the Evangelical Lutheran Church in America . It is the seat of several dioceses . The Fourth Presbyterian Church is one of the largest Presbyterian congregations in the United States based on memberships. Since the 20th century Chicago has also been the headquarters of the Assyrian Church of the East . In 2014 the Catholic Church was the largest individual Christian denomination (34%), with the Roman Catholic Archdiocese of Chicago being the largest Catholic jurisdiction. Evangelical Protestantism form the largest theological Protestant branch (16%), followed by Mainline Protestants (11%), and historically Black churches (8%). Among denominational Protestant branches, Baptists formed the largest group in Chicago (10%); followed by Nondenominational (5%); Lutherans (4%); and Pentecostals (3%). Non-Christian faiths accounted for 7% of the religious population in 2014. Judaism has at least 261,000 adherents which is 3% of the population, making it the second largest religion. A 2020 study estimated the total Jewish population of the Chicago metropolitan area, both religious and irreligious, at 319,500. The first two Parliament of the World's Religions in 1893 and 1993 were held in Chicago. Many international religious leaders have visited Chicago, including Mother Teresa , the Dalai Lama and Pope John Paul II in 1979. Chicago has the third-largest gross metropolitan product in the United States—about $670.5 billion according to September 2017 estimates. The city has also been rated as having the most balanced economy in the United States, due to its high level of diversification. The Chicago metropolitan area has the third-largest science and engineering work force of any metropolitan area in the nation. Chicago was the base of commercial operations for industrialists John Crerar , John Whitfield Bunn , Richard Teller Crane , Marshall Field , John Farwell , Julius Rosenwald , and many other commercial visionaries who laid the foundation for Midwestern and global industry. Chicago is a major world financial center, with the second-largest central business district in the United States, following Midtown Manhattan . The city is the seat of the Federal Reserve Bank of Chicago , the Bank's Seventh District. The city has major financial and futures exchanges , including the Chicago Stock Exchange , the Chicago Board Options Exchange (CBOE), and the Chicago Mercantile Exchange (the "Merc"), which is owned, along with the Chicago Board of Trade (CBOT), by Chicago's CME Group . In 2017, Chicago exchanges traded 4.7 billion in derivatives. [ citation needed ] Chase Bank has its commercial and retail banking headquarters in Chicago's Chase Tower . Academically, Chicago has been influential through the Chicago school of economics , which fielded 12 Nobel Prize winners. The city and its surrounding metropolitan area contain the third-largest labor pool in the United States with about 4.63 million workers. Illinois is home to 66 Fortune 1000 companies, including those in Chicago. The city of Chicago also hosts 12 Fortune Global 500 companies and 17 Financial Times 500 companies. The city claims three Dow 30 companies: aerospace giant Boeing , which moved its headquarters from Seattle to the Chicago Loop in 2001; McDonald's ; and Walgreens Boots Alliance . For six consecutive years from 2013 through 2018, Chicago was ranked the nation's top metropolitan area for corporate relocations. However, three Fortune 500 companies left Chicago in 2022, leaving the city with 35, still second to New York City. Manufacturing, printing, publishing, and food processing also play major roles in the city's economy. Several medical products and services companies are headquartered in the Chicago area, including Baxter International , Boeing , Abbott Laboratories , and the Healthcare division of General Electric . Prominent food companies based in Chicago include the world headquarters of Conagra , Ferrara Candy Company , Kraft Heinz , McDonald's , Mondelez International , and Quaker Oats . [ citation needed ] Chicago has been a hub of the retail sector since its early development, with Montgomery Ward , Sears , and Marshall Field's . Today the Chicago metropolitan area is the headquarters of several retailers, including Walgreens , Sears , Ace Hardware , Claire's , ULTA Beauty , and Crate & Barrel . [ citation needed ] Late in the 19th century, Chicago was part of the bicycle craze , with the Western Wheel Company, which introduced stamping to the production process and significantly reduced costs, while early in the 20th century, the city was part of the automobile revolution, hosting the Brass Era car builder Bugmobile, which was founded there in 1907. Chicago was also the site of the Schwinn Bicycle Company . Chicago is a major world convention destination. The city's main convention center is McCormick Place. With its four interconnected buildings, it is the largest convention center in the nation and third-largest in the world. Chicago also ranks third in the U.S. (behind Las Vegas and Orlando ) in number of conventions hosted annually. Chicago's minimum wage for non-tipped employees is one of the highest in the nation and reached $15 in 2021. The city's waterfront location and nightlife has attracted residents and tourists alike. Over a third of the city population is concentrated in the lakefront neighborhoods from Rogers Park in the north to South Shore in the south. The city has many upscale dining establishments as well as many ethnic restaurant districts. These districts include the Mexican American neighborhoods, such as Pilsen along 18th street, and La Villita along 26th Street; the Puerto Rican enclave of Paseo Boricua in the Humboldt Park neighborhood; Greektown , along South Halsted Street , immediately west of downtown; Little Italy , along Taylor Street; Chinatown in Armour Square ; Polish Patches in West Town ; Little Seoul in Albany Park around Lawrence Avenue; Little Vietnam near Broadway in Uptown; and the Desi area, along Devon Avenue in West Ridge . Downtown is the center of Chicago's financial, cultural, governmental and commercial institutions and the site of Grant Park and many of the city's skyscrapers. Many of the city's financial institutions, such as the CBOT and the Federal Reserve Bank of Chicago, are located within a section of downtown called "The Loop", which is an eight-block by five-block area of city streets that is encircled by elevated rail tracks. The term "The Loop" is largely used by locals to refer to the entire downtown area as well. The central area includes the Near North Side , the Near South Side , and the Near West Side , as well as the Loop. These areas contribute famous skyscrapers , abundant restaurants, shopping , museums , a stadium for the Chicago Bears , convention facilities, parkland , and beaches . [ citation needed ] Lincoln Park contains the Lincoln Park Zoo and the Lincoln Park Conservatory . The River North Gallery District features the nation's largest concentration of contemporary art galleries outside of New York City. [ citation needed ] Lakeview is home to Boystown , the city's large LGBT nightlife and culture center. The Chicago Pride Parade , held the last Sunday in June, is one of the world's largest with over a million people in attendance. North Halsted Street is the main thoroughfare of Boystown. The South Side neighborhood of Hyde Park is the home of former U.S. President Barack Obama . It also contains the University of Chicago, ranked one of the world's top ten universities, and the Museum of Science and Industry . The 6-mile (9.7 km) long Burnham Park stretches along the waterfront of the South Side. Two of the city's largest parks are also located on this side of the city: Jackson Park, bordering the waterfront, hosted the World's Columbian Exposition in 1893, and is the site of the aforementioned museum; and slightly west sits Washington Park . The two parks themselves are connected by a wide strip of parkland called the Midway Plaisance , running adjacent to the University of Chicago. The South Side hosts one of the city's largest parades, the annual African American Bud Billiken Parade and Picnic , which travels through Bronzeville to Washington Park. Ford Motor Company has an automobile assembly plant on the South Side in Hegewisch , and most of the facilities of the Port of Chicago are also on the South Side. [ citation needed ] The West Side holds the Garfield Park Conservatory , one of the largest collections of tropical plants in any U.S. city. Prominent Latino cultural attractions found here include Humboldt Park 's Institute of Puerto Rican Arts and Culture and the annual Puerto Rican People's Parade, as well as the National Museum of Mexican Art and St. Adalbert's Church in Pilsen . The Near West Side holds the University of Illinois at Chicago and was once home to Oprah Winfrey 's Harpo Studios , the site of which has been rebuilt as the global headquarters of McDonald's. [ citation needed ] The city's distinctive accent, made famous by its use in classic films like The Blues Brothers and television programs like the Saturday Night Live skit " Bill Swerski's Superfans ", is an advanced form of Inland Northern American English . This dialect can also be found in other cities bordering the Great Lakes such as Cleveland , Milwaukee , Detroit , and Rochester, New York , and most prominently features a rearrangement of certain vowel sounds, such as the short 'a' sound as in "cat," which can sound more like "kyet" to outsiders. The accent remains well associated with the city. Renowned Chicago theater companies include the Goodman Theatre in the Loop; the Steppenwolf Theatre Company and Victory Gardens Theater in Lincoln Park; and the Chicago Shakespeare Theater at Navy Pier. Broadway In Chicago offers Broadway-style entertainment at five theaters: the Nederlander Theatre , CIBC Theatre , Cadillac Palace Theatre , Auditorium Building of Roosevelt University , and Broadway Playhouse at Water Tower Place . Polish language productions for Chicago's large Polish speaking population can be seen at the historic Gateway Theatre in Jefferson Park . Since 1968, the Joseph Jefferson Awards are given annually to acknowledge excellence in theater in the Chicago area. Chicago's theater community spawned modern improvisational theater , and includes the prominent groups The Second City and I.O. (formerly ImprovOlympic). [ citation needed ] The Chicago Symphony Orchestra (CSO) performs at Symphony Center , and is recognized as one of the best orchestras in the world. Also performing regularly at Symphony Center is the Chicago Sinfonietta , a more diverse and multicultural counterpart to the CSO. In the summer, many outdoor concerts are given in Grant Park and Millennium Park . Ravinia Festival , located 25 miles (40 km) north of Chicago, is the summer home of the CSO, and is a favorite destination for many Chicagoans. The Civic Opera House is home to the Lyric Opera of Chicago . The Lithuanian Opera Company of Chicago was founded by Lithuanian Chicagoans in 1956, and presents operas in Lithuanian . The Joffrey Ballet and Chicago Festival Ballet perform in various venues, including the Harris Theater in Millennium Park . Chicago has several other contemporary and jazz dance troupes, such as the Hubbard Street Dance Chicago and Chicago Dance Crash . [ citation needed ] Other live-music genre which are part of the city's cultural heritage include Chicago blues , Chicago soul , jazz , and gospel . The city is the birthplace of house music (a popular form of electronic dance music) and industrial music , and is the site of an influential hip hop scene . In the 1980s and 90s, the city was the global center for house and industrial music, two forms of music created in Chicago, as well as being popular for alternative rock , punk , and new wave . The city has been a center for rave culture, since the 1980s. A flourishing independent rock music culture brought forth Chicago indie . Annual festivals feature various acts, such as Lollapalooza and the Pitchfork Music Festival . [ citation needed ] Lollapalooza originated in Chicago in 1991 and at first travelled to many cities, but as of 2005 its home has been Chicago. A 2007 report on the Chicago music industry by the University of Chicago Cultural Policy Center ranked Chicago third among metropolitan U.S. areas in "size of music industry" and fourth among all U.S. cities in "number of concerts and performances". Chicago has a distinctive fine art tradition. For much of the twentieth century, it nurtured a strong style of figurative surrealism , as in the works of Ivan Albright and Ed Paschke . In 1968 and 1969, members of the Chicago Imagists , such as Roger Brown , Leon Golub , Robert Lostutter , Jim Nutt , and Barbara Rossi produced bizarre representational paintings. Henry Darger is one of the most celebrated figures of outsider art . In 2014 [ update ] , Chicago attracted 50.17 million domestic leisure travelers, 11.09 million domestic business travelers and 1.308 million overseas visitors. These visitors contributed more than US$13.7 billion to Chicago's economy. Upscale shopping along the Magnificent Mile and State Street, thousands of restaurants, as well as Chicago's eminent architecture, continue to draw tourists. The city is the United States' third-largest convention destination. A 2017 study by Walk Score ranked Chicago the sixth-most walkable of fifty largest cities in the United States. Most conventions are held at McCormick Place, just south of Soldier Field . Navy Pier, located just east of Streeterville , is 3,000 ft (910 m) long and houses retail stores, restaurants, museums, exhibition halls and auditoriums. Chicago was the first city in the world to ever erect a ferris wheel. The Willis Tower (formerly named Sears Tower) is a popular destination for tourists. Among the city's museums are the Adler Planetarium & Astronomy Museum , the Field Museum of Natural History , and the Shedd Aquarium . The Museum Campus joins the southern section of Grant Park, which includes the renowned Art Institute of Chicago. Buckingham Fountain anchors the downtown park along the lakefront. The University of Chicago's Institute for the Study of Ancient Cultures, West Asia & North Africa has an extensive collection of ancient Egyptian and Near Eastern archaeological artifacts. Other museums and galleries in Chicago include the Chicago History Museum , the Driehaus Museum , the DuSable Museum of African American History , the Museum of Contemporary Art , the Peggy Notebaert Nature Museum , the Polish Museum of America , the Museum of Broadcast Communications , the Pritzker Military Library , the Chicago Architecture Foundation , and the Museum of Science and Industry . [ citation needed ] Chicago lays claim to a large number of regional specialties that reflect the city's ethnic and working-class roots. Included among these are its nationally renowned deep-dish pizza ; this style is said to have originated at Pizzeria Uno . The Chicago-style thin crust is also popular in the city. Certain Chicago pizza favorites include Lou Malnati's and Giordano's . The Chicago-style hot dog , typically an all-beef hot dog, is loaded with an array of toppings that often includes pickle relish, yellow mustard , pickled sport peppers , tomato wedges, dill pickle spear and topped off with celery salt on a poppy seed bun . Enthusiasts of the Chicago-style hot dog frown upon the use of ketchup as a garnish, but may prefer to add giardiniera . A distinctly Chicago sandwich, the Italian beef sandwich is thinly sliced beef simmered in au jus and served on an Italian roll with sweet peppers or spicy giardiniera. A popular modification is the Combo—an Italian beef sandwich with the addition of an Italian sausage. The Maxwell Street Polish is a grilled or deep-fried kielbasa —on a hot dog roll, topped with grilled onions, yellow mustard, and hot sport peppers. Chicken Vesuvio is roasted bone-in chicken cooked in oil and garlic next to garlicky oven-roasted potato wedges and a sprinkling of green peas. The Puerto Rican -influenced jibarito is a sandwich made with flattened, fried green plantains instead of bread. The mother-in-law is a tamale topped with chili and served on a hot dog bun. The tradition of serving the Greek dish saganaki while aflame has its origins in Chicago's Greek community. The appetizer, which consists of a square of fried cheese, is doused with Metaxa and flambéed table-side. Chicago-style barbecue features hardwood smoked rib tips and hot links which were traditionally cooked in an aquarium smoker, a Chicago invention. Annual festivals feature various Chicago signature dishes, such as Taste of Chicago and the Chicago Food Truck Festival. One of the world's most decorated restaurants and a recipient of three Michelin stars, Alinea is located in Chicago. Well-known chefs who have had restaurants in Chicago include: Charlie Trotter , Rick Tramonto , Grant Achatz , and Rick Bayless . In 2003, Robb Report named Chicago the country's "most exceptional dining destination". Chicago literature finds its roots in the city's tradition of lucid, direct journalism, lending to a strong tradition of social realism . In the Encyclopedia of Chicago , Northwestern University Professor Bill Savage describes Chicago fiction as prose which tries to "capture the essence of the city, its spaces and its people." The challenge for early writers was that Chicago was a frontier outpost that transformed into a global metropolis in the span of two generations. Narrative fiction of that time, much of it in the style of "high-flown romance" and "genteel realism", needed a new approach to describe the urban social, political, and economic conditions of Chicago. Nonetheless, Chicagoans worked hard to create a literary tradition that would stand the test of time, and create a "city of feeling" out of concrete, steel, vast lake, and open prairie. Much notable Chicago fiction focuses on the city itself, with social criticism keeping exultation in check. At least three short periods in the history of Chicago have had a lasting influence on American literature . These include from the time of the Great Chicago Fire to about 1900, what became known as the Chicago Literary Renaissance in the 1910s and early 1920s, and the period of the Great Depression through the 1940s. What would become the influential Poetry magazine was founded in 1912 by Harriet Monroe , who was working as an art critic for the Chicago Tribune . The magazine discovered such poets as Gwendolyn Brooks , James Merrill , and John Ashbery . T. S. Eliot 's first professionally published poem, " The Love Song of J. Alfred Prufrock ", was first published by Poetry . Contributors have included Ezra Pound , William Butler Yeats , William Carlos Williams , Langston Hughes , and Carl Sandburg , among others. The magazine was instrumental in launching the Imagist and Objectivist poetic movements. From the 1950s through 1970s, American poetry continued to evolve in Chicago. In the 1980s, a modern form of poetry performance began in Chicago, the poetry slam . Renowned Chicago theater companies include the Goodman Theatre in the Loop; the Steppenwolf Theatre Company and Victory Gardens Theater in Lincoln Park; and the Chicago Shakespeare Theater at Navy Pier. Broadway In Chicago offers Broadway-style entertainment at five theaters: the Nederlander Theatre , CIBC Theatre , Cadillac Palace Theatre , Auditorium Building of Roosevelt University , and Broadway Playhouse at Water Tower Place . Polish language productions for Chicago's large Polish speaking population can be seen at the historic Gateway Theatre in Jefferson Park . Since 1968, the Joseph Jefferson Awards are given annually to acknowledge excellence in theater in the Chicago area. Chicago's theater community spawned modern improvisational theater , and includes the prominent groups The Second City and I.O. (formerly ImprovOlympic). [ citation needed ] The Chicago Symphony Orchestra (CSO) performs at Symphony Center , and is recognized as one of the best orchestras in the world. Also performing regularly at Symphony Center is the Chicago Sinfonietta , a more diverse and multicultural counterpart to the CSO. In the summer, many outdoor concerts are given in Grant Park and Millennium Park . Ravinia Festival , located 25 miles (40 km) north of Chicago, is the summer home of the CSO, and is a favorite destination for many Chicagoans. The Civic Opera House is home to the Lyric Opera of Chicago . The Lithuanian Opera Company of Chicago was founded by Lithuanian Chicagoans in 1956, and presents operas in Lithuanian . The Joffrey Ballet and Chicago Festival Ballet perform in various venues, including the Harris Theater in Millennium Park . Chicago has several other contemporary and jazz dance troupes, such as the Hubbard Street Dance Chicago and Chicago Dance Crash . [ citation needed ] Other live-music genre which are part of the city's cultural heritage include Chicago blues , Chicago soul , jazz , and gospel . The city is the birthplace of house music (a popular form of electronic dance music) and industrial music , and is the site of an influential hip hop scene . In the 1980s and 90s, the city was the global center for house and industrial music, two forms of music created in Chicago, as well as being popular for alternative rock , punk , and new wave . The city has been a center for rave culture, since the 1980s. A flourishing independent rock music culture brought forth Chicago indie . Annual festivals feature various acts, such as Lollapalooza and the Pitchfork Music Festival . [ citation needed ] Lollapalooza originated in Chicago in 1991 and at first travelled to many cities, but as of 2005 its home has been Chicago. A 2007 report on the Chicago music industry by the University of Chicago Cultural Policy Center ranked Chicago third among metropolitan U.S. areas in "size of music industry" and fourth among all U.S. cities in "number of concerts and performances". Chicago has a distinctive fine art tradition. For much of the twentieth century, it nurtured a strong style of figurative surrealism , as in the works of Ivan Albright and Ed Paschke . In 1968 and 1969, members of the Chicago Imagists , such as Roger Brown , Leon Golub , Robert Lostutter , Jim Nutt , and Barbara Rossi produced bizarre representational paintings. Henry Darger is one of the most celebrated figures of outsider art . In 2014 [ update ] , Chicago attracted 50.17 million domestic leisure travelers, 11.09 million domestic business travelers and 1.308 million overseas visitors. These visitors contributed more than US$13.7 billion to Chicago's economy. Upscale shopping along the Magnificent Mile and State Street, thousands of restaurants, as well as Chicago's eminent architecture, continue to draw tourists. The city is the United States' third-largest convention destination. A 2017 study by Walk Score ranked Chicago the sixth-most walkable of fifty largest cities in the United States. Most conventions are held at McCormick Place, just south of Soldier Field . Navy Pier, located just east of Streeterville , is 3,000 ft (910 m) long and houses retail stores, restaurants, museums, exhibition halls and auditoriums. Chicago was the first city in the world to ever erect a ferris wheel. The Willis Tower (formerly named Sears Tower) is a popular destination for tourists. Among the city's museums are the Adler Planetarium & Astronomy Museum , the Field Museum of Natural History , and the Shedd Aquarium . The Museum Campus joins the southern section of Grant Park, which includes the renowned Art Institute of Chicago. Buckingham Fountain anchors the downtown park along the lakefront. The University of Chicago's Institute for the Study of Ancient Cultures, West Asia & North Africa has an extensive collection of ancient Egyptian and Near Eastern archaeological artifacts. Other museums and galleries in Chicago include the Chicago History Museum , the Driehaus Museum , the DuSable Museum of African American History , the Museum of Contemporary Art , the Peggy Notebaert Nature Museum , the Polish Museum of America , the Museum of Broadcast Communications , the Pritzker Military Library , the Chicago Architecture Foundation , and the Museum of Science and Industry . [ citation needed ]Chicago lays claim to a large number of regional specialties that reflect the city's ethnic and working-class roots. Included among these are its nationally renowned deep-dish pizza ; this style is said to have originated at Pizzeria Uno . The Chicago-style thin crust is also popular in the city. Certain Chicago pizza favorites include Lou Malnati's and Giordano's . The Chicago-style hot dog , typically an all-beef hot dog, is loaded with an array of toppings that often includes pickle relish, yellow mustard , pickled sport peppers , tomato wedges, dill pickle spear and topped off with celery salt on a poppy seed bun . Enthusiasts of the Chicago-style hot dog frown upon the use of ketchup as a garnish, but may prefer to add giardiniera . A distinctly Chicago sandwich, the Italian beef sandwich is thinly sliced beef simmered in au jus and served on an Italian roll with sweet peppers or spicy giardiniera. A popular modification is the Combo—an Italian beef sandwich with the addition of an Italian sausage. The Maxwell Street Polish is a grilled or deep-fried kielbasa —on a hot dog roll, topped with grilled onions, yellow mustard, and hot sport peppers. Chicken Vesuvio is roasted bone-in chicken cooked in oil and garlic next to garlicky oven-roasted potato wedges and a sprinkling of green peas. The Puerto Rican -influenced jibarito is a sandwich made with flattened, fried green plantains instead of bread. The mother-in-law is a tamale topped with chili and served on a hot dog bun. The tradition of serving the Greek dish saganaki while aflame has its origins in Chicago's Greek community. The appetizer, which consists of a square of fried cheese, is doused with Metaxa and flambéed table-side. Chicago-style barbecue features hardwood smoked rib tips and hot links which were traditionally cooked in an aquarium smoker, a Chicago invention. Annual festivals feature various Chicago signature dishes, such as Taste of Chicago and the Chicago Food Truck Festival. One of the world's most decorated restaurants and a recipient of three Michelin stars, Alinea is located in Chicago. Well-known chefs who have had restaurants in Chicago include: Charlie Trotter , Rick Tramonto , Grant Achatz , and Rick Bayless . In 2003, Robb Report named Chicago the country's "most exceptional dining destination". Chicago literature finds its roots in the city's tradition of lucid, direct journalism, lending to a strong tradition of social realism . In the Encyclopedia of Chicago , Northwestern University Professor Bill Savage describes Chicago fiction as prose which tries to "capture the essence of the city, its spaces and its people." The challenge for early writers was that Chicago was a frontier outpost that transformed into a global metropolis in the span of two generations. Narrative fiction of that time, much of it in the style of "high-flown romance" and "genteel realism", needed a new approach to describe the urban social, political, and economic conditions of Chicago. Nonetheless, Chicagoans worked hard to create a literary tradition that would stand the test of time, and create a "city of feeling" out of concrete, steel, vast lake, and open prairie. Much notable Chicago fiction focuses on the city itself, with social criticism keeping exultation in check. At least three short periods in the history of Chicago have had a lasting influence on American literature . These include from the time of the Great Chicago Fire to about 1900, what became known as the Chicago Literary Renaissance in the 1910s and early 1920s, and the period of the Great Depression through the 1940s. What would become the influential Poetry magazine was founded in 1912 by Harriet Monroe , who was working as an art critic for the Chicago Tribune . The magazine discovered such poets as Gwendolyn Brooks , James Merrill , and John Ashbery . T. S. Eliot 's first professionally published poem, " The Love Song of J. Alfred Prufrock ", was first published by Poetry . Contributors have included Ezra Pound , William Butler Yeats , William Carlos Williams , Langston Hughes , and Carl Sandburg , among others. The magazine was instrumental in launching the Imagist and Objectivist poetic movements. From the 1950s through 1970s, American poetry continued to evolve in Chicago. In the 1980s, a modern form of poetry performance began in Chicago, the poetry slam . The city has two Major League Baseball (MLB) teams: the Chicago Cubs of the National League play in Wrigley Field on the North Side; and the Chicago White Sox of the American League play in Guaranteed Rate Field on the South Side. The two teams have faced each other in a World Series only once, in 1906. The Cubs are the oldest Major League Baseball team to have never changed their city; they have played in Chicago since 1871. They had the dubious honor of having the longest championship drought in American professional sports, failing to win a World Series between 1908 and 2016. The White Sox have played on the South Side continuously since 1901. They have won three World Series titles (1906, 1917, 2005) and six American League pennants, including the first in 1901. The Chicago Bears , one of the last two remaining charter members of the National Football League (NFL), have won nine NFL Championships , including the 1985 Super Bowl XX . The Bears play their home games at Soldier Field. The Chicago Bulls of the National Basketball Association (NBA) is one of the most recognized basketball teams in the world. During the 1990s, with Michael Jordan leading them, the Bulls won six NBA championships in eight seasons. The Chicago Blackhawks of the National Hockey League (NHL) began play in 1926, and are one of the " Original Six " teams of the NHL. The Blackhawks have won six Stanley Cups , including in 2010, 2013, and 2015 . Both the Bulls and the Blackhawks play at the United Center . Chicago Fire FC is a member of Major League Soccer (MLS) and plays at Soldier Field. The Fire have won one league title and four U.S. Open Cups , since their founding in 1997. In 1994, the United States hosted a successful FIFA World Cup with games played at Soldier Field. The Chicago Red Stars are a team in the National Women's Soccer League (NWSL). They previously played in Women's Professional Soccer (WPS), of which they were a founding member, before joining the NWSL in 2013. They play at SeatGeek Stadium in Bridgeview, Illinois . The Chicago Sky is a professional basketball team playing in the Women's National Basketball Association (WNBA). They play home games at the Wintrust Arena . The team was founded before the 2006 WNBA season began. The Chicago Marathon has been held each year since 1977 except for 1987, when a half marathon was run in its place. The Chicago Marathon is one of six World Marathon Majors . Five area colleges play in Division I conferences: two from major conferences—the DePaul Blue Demons ( Big East Conference ) and the Northwestern Wildcats ( Big Ten Conference )—and three from other D1 conferences—the Chicago State Cougars ( Western Athletic Conference ); the Loyola Ramblers ( Atlantic 10 Conference ); and the UIC Flames ( Missouri Valley Conference ). Chicago has also entered into esports with the creation of the Chicago Huntsmen , a professional Call of Duty team that participates within the CDL . [ citation needed ]When Chicago was incorporated in 1837, it chose the motto Urbs in Horto , a Latin phrase which means "City in a Garden". Today, the Chicago Park District consists of more than 570 parks with over 8,000 acres (3,200 ha) of municipal parkland . There are 31 sand beaches , a plethora of museums, two world-class conservatories, and 50 nature areas. Lincoln Park, the largest of the city's parks, covers 1,200 acres (490 ha) and has over 20 million visitors each year, making it third in the number of visitors after Central Park in New York City , and the National Mall and Memorial Parks in Washington, D.C. There is a historic boulevard system , a network of wide, tree-lined boulevards which connect a number of Chicago parks . The boulevards and the parks were authorized by the Illinois legislature in 1869. A number of Chicago neighborhoods emerged along these roadways in the 19th century. The building of the boulevard system continued intermittently until 1942. It includes nineteen boulevards, eight parks, and six squares , along twenty-six miles of interconnected streets. The Chicago Park Boulevard System Historic District was listed on the National Register of Historic Places in 2018. With berths for more than 6,000 boats, the Chicago Park District operates the nation's largest municipal harbor system. In addition to ongoing beautification and renewal projects for the existing parks, a number of new parks have been added in recent years, such as the Ping Tom Memorial Park in Chinatown, DuSable Park on the Near North Side, and most notably, Millennium Park, which is in the northwestern corner of one of Chicago's oldest parks, Grant Park in the Chicago Loop. [ citation needed ] The wealth of greenspace afforded by Chicago's parks is further augmented by the Cook County Forest Preserves , a network of open spaces containing forest, prairie , wetland , streams, and lakes that are set aside as natural areas which lie along the city's outskirts, including both the Chicago Botanic Garden in Glencoe and the Brookfield Zoo in Brookfield . Washington Park is also one of the city's biggest parks; covering nearly 400 acres (160 ha) . The park is listed on the National Register of Historic Places listings in South Side Chicago . The government of the City of Chicago is divided into executive and legislative branches. The mayor of Chicago is the chief executive, elected by general election for a term of four years, with no term limits. The current mayor is Brandon Johnson . The mayor appoints commissioners and other officials who oversee the various departments. As well as the mayor, Chicago's clerk and treasurer are also elected citywide. The City Council is the legislative branch and is made up of 50 alderpersons, one elected from each ward in the city. The council takes official action through the passage of ordinances and resolutions and approves the city budget. The Chicago Police Department provides law enforcement and the Chicago Fire Department provides fire suppression and emergency medical services for the city and its residents. Civil and criminal law cases are heard in the Cook County Circuit Court of the State of Illinois court system, or in the Northern District of Illinois , in the federal system. In the state court, the public prosecutor is the Illinois state's attorney ; in the Federal court it is the United States attorney . During much of the last half of the 19th century, Chicago's politics were dominated by a growing Democratic Party organization. During the 1880s and 1890s, Chicago had a powerful radical tradition with large and highly organized socialist , anarchist and labor organizations . For much of the 20th century, Chicago has been among the largest and most reliable Democratic strongholds in the United States; with Chicago's Democratic vote the state of Illinois has been " solid blue " in presidential elections since 1992. Even before then, it was not unheard of for Republican presidential candidates to win handily in downstate Illinois, only to lose statewide due to large Democratic margins in Chicago. The citizens of Chicago have not elected a Republican mayor since 1927, when William Thompson was voted into office. The strength of the party in the city is partly a consequence of Illinois state politics, where the Republicans have come to represent rural and farm concerns while the Democrats support urban issues such as Chicago's public school funding. [ citation needed ] Chicago contains less than 25% of the state's population, but it is split between eight of Illinois' 17 districts in the United States House of Representatives . All eight of the city's representatives are Democrats; only two Republicans have represented a significant portion of the city since 1973, for one term each: Robert P. Hanrahan from 1973 to 1975, and Michael Patrick Flanagan from 1995 to 1997. [ citation needed ] Machine politics persisted in Chicago after the decline of similar machines in other large U.S. cities. During much of that time, the city administration found opposition mainly from a liberal "independent" faction of the Democratic Party. The independents finally gained control of city government in 1983 with the election of Harold Washington (in office 1983–1987). From 1989 until May 16, 2011, Chicago was under the leadership of its longest-serving mayor, Richard M. Daley , the son of Richard J. Daley. Because of the dominance of the Democratic Party in Chicago, the Democratic primary vote held in the spring is generally more significant than the general elections in November for U.S. House and Illinois State seats. The aldermanic, mayoral, and other city offices are filled through nonpartisan elections with runoffs as needed. The city is home of former United States President Barack Obama and First Lady Michelle Obama ; Barack Obama was formerly a state legislator representing Chicago and later a U.S. senator. The Obamas' residence is located near the University of Chicago in Kenwood on the city's south side. Chicago's crime rate in 2020 was 3,926 per 100,000 people. Chicago experienced major rises in violent crime in the 1920s, in the late 1960s, and in the 2020s. Chicago's biggest criminal justice challenges have changed little over the last 50 years, and statistically reside with homicide, armed robbery , gang violence, and aggravated battery . Chicago has attracted attention for a high murder rate and perceived crime rate compared to other major cities like New York and Los Angeles. However, while it has a large absolute number of crimes due to its size, Chicago is not among the top-25 most violent cities in the United States. Murder rates in Chicago vary greatly depending on the neighborhood in question. The neighborhoods of Englewood on the South Side, and Austin on the West side, for example, have homicide rates that are ten times higher than other parts of the city. Chicago has an estimated population of over 100,000 active gang members from nearly 60 factions. According to reports in 2013, "most of Chicago's violent crime comes from gangs trying to maintain control of drug-selling territories," and is specifically related to the activities of the Sinaloa Cartel , which is active in several American cities. Violent crime rates vary significantly by area of the city, with more economically developed areas having low rates, but other sections have much higher rates of crime. In 2013, the violent crime rate was 910 per 100,000 people; the murder rate was 10.4 – while high crime districts saw 38.9, low crime districts saw 2.5 murders per 100,000. Chicago has a long history of public corruption that regularly draws the attention of federal law enforcement and federal prosecutors. From 2012 to 2019, 33 Chicago alderpersons were convicted on corruption charges, roughly one third of those elected in the time period. A report from the Office of the Legislative Inspector General noted that over half of Chicago's elected alderpersons took illegal campaign contributions in 2013. Most corruption cases in Chicago are prosecuted by the U.S. Attorney 's office, as legal jurisdiction makes most offenses punishable as a federal crime. The government of the City of Chicago is divided into executive and legislative branches. The mayor of Chicago is the chief executive, elected by general election for a term of four years, with no term limits. The current mayor is Brandon Johnson . The mayor appoints commissioners and other officials who oversee the various departments. As well as the mayor, Chicago's clerk and treasurer are also elected citywide. The City Council is the legislative branch and is made up of 50 alderpersons, one elected from each ward in the city. The council takes official action through the passage of ordinances and resolutions and approves the city budget. The Chicago Police Department provides law enforcement and the Chicago Fire Department provides fire suppression and emergency medical services for the city and its residents. Civil and criminal law cases are heard in the Cook County Circuit Court of the State of Illinois court system, or in the Northern District of Illinois , in the federal system. In the state court, the public prosecutor is the Illinois state's attorney ; in the Federal court it is the United States attorney .During much of the last half of the 19th century, Chicago's politics were dominated by a growing Democratic Party organization. During the 1880s and 1890s, Chicago had a powerful radical tradition with large and highly organized socialist , anarchist and labor organizations . For much of the 20th century, Chicago has been among the largest and most reliable Democratic strongholds in the United States; with Chicago's Democratic vote the state of Illinois has been " solid blue " in presidential elections since 1992. Even before then, it was not unheard of for Republican presidential candidates to win handily in downstate Illinois, only to lose statewide due to large Democratic margins in Chicago. The citizens of Chicago have not elected a Republican mayor since 1927, when William Thompson was voted into office. The strength of the party in the city is partly a consequence of Illinois state politics, where the Republicans have come to represent rural and farm concerns while the Democrats support urban issues such as Chicago's public school funding. [ citation needed ] Chicago contains less than 25% of the state's population, but it is split between eight of Illinois' 17 districts in the United States House of Representatives . All eight of the city's representatives are Democrats; only two Republicans have represented a significant portion of the city since 1973, for one term each: Robert P. Hanrahan from 1973 to 1975, and Michael Patrick Flanagan from 1995 to 1997. [ citation needed ] Machine politics persisted in Chicago after the decline of similar machines in other large U.S. cities. During much of that time, the city administration found opposition mainly from a liberal "independent" faction of the Democratic Party. The independents finally gained control of city government in 1983 with the election of Harold Washington (in office 1983–1987). From 1989 until May 16, 2011, Chicago was under the leadership of its longest-serving mayor, Richard M. Daley , the son of Richard J. Daley. Because of the dominance of the Democratic Party in Chicago, the Democratic primary vote held in the spring is generally more significant than the general elections in November for U.S. House and Illinois State seats. The aldermanic, mayoral, and other city offices are filled through nonpartisan elections with runoffs as needed. The city is home of former United States President Barack Obama and First Lady Michelle Obama ; Barack Obama was formerly a state legislator representing Chicago and later a U.S. senator. The Obamas' residence is located near the University of Chicago in Kenwood on the city's south side. Chicago's crime rate in 2020 was 3,926 per 100,000 people. Chicago experienced major rises in violent crime in the 1920s, in the late 1960s, and in the 2020s. Chicago's biggest criminal justice challenges have changed little over the last 50 years, and statistically reside with homicide, armed robbery , gang violence, and aggravated battery . Chicago has attracted attention for a high murder rate and perceived crime rate compared to other major cities like New York and Los Angeles. However, while it has a large absolute number of crimes due to its size, Chicago is not among the top-25 most violent cities in the United States. Murder rates in Chicago vary greatly depending on the neighborhood in question. The neighborhoods of Englewood on the South Side, and Austin on the West side, for example, have homicide rates that are ten times higher than other parts of the city. Chicago has an estimated population of over 100,000 active gang members from nearly 60 factions. According to reports in 2013, "most of Chicago's violent crime comes from gangs trying to maintain control of drug-selling territories," and is specifically related to the activities of the Sinaloa Cartel , which is active in several American cities. Violent crime rates vary significantly by area of the city, with more economically developed areas having low rates, but other sections have much higher rates of crime. In 2013, the violent crime rate was 910 per 100,000 people; the murder rate was 10.4 – while high crime districts saw 38.9, low crime districts saw 2.5 murders per 100,000. Chicago has a long history of public corruption that regularly draws the attention of federal law enforcement and federal prosecutors. From 2012 to 2019, 33 Chicago alderpersons were convicted on corruption charges, roughly one third of those elected in the time period. A report from the Office of the Legislative Inspector General noted that over half of Chicago's elected alderpersons took illegal campaign contributions in 2013. Most corruption cases in Chicago are prosecuted by the U.S. Attorney 's office, as legal jurisdiction makes most offenses punishable as a federal crime. Chicago Public Schools (CPS) is the governing body of the school district that contains over 600 public elementary and high schools citywide, including several selective-admission magnet schools. There are eleven selective enrollment high schools in the Chicago Public Schools, designed to meet the needs of Chicago's most academically advanced students. These schools offer a rigorous curriculum with mainly honors and Advanced Placement (AP) courses. Walter Payton College Prep High School is ranked number one in the city of Chicago and the state of Illinois. Chicago high school rankings are determined by the average test scores on state achievement tests. The district, with an enrollment exceeding 400,545 students (2013–2014 20th Day Enrollment), is the third-largest in the U.S. On September 10, 2012, teachers for the Chicago Teachers Union went on strike for the first time since 1987 over pay, resources and other issues. According to data compiled in 2014, Chicago's "choice system", where students who test or apply and may attend one of a number of public high schools (there are about 130), sorts students of different achievement levels into different schools (high performing, middle performing, and low performing schools). Chicago has a network of Lutheran schools , and several private schools are run by other denominations and faiths, such as the Ida Crown Jewish Academy in West Ridge . The Roman Catholic Archdiocese of Chicago operates Catholic schools , that include Jesuit preparatory schools and others. A number of private schools are completely secular. There are also the private Chicago Academy for the Arts , a high school focused on six different categories of the arts and the public Chicago High School for the Arts , a high school focused on five categories (visual arts, theatre, musical theatre, dance, and music) of the arts. The Chicago Public Library system operates three regional libraries and 77 neighbourhood branches, including the central library. Since the 1850s, Chicago has been a world center of higher education and research with several universities. These institutions consistently rank among the top "National Universities" in the United States, as determined by U.S. News & World Report . Highly regarded universities in Chicago and the surrounding area are: the University of Chicago; Northwestern University; Illinois Institute of Technology ; Loyola University Chicago ; DePaul University ; Columbia College Chicago and University of Illinois at Chicago. Other notable schools include: Chicago State University ; the School of the Art Institute of Chicago ; East–West University ; National Louis University ; North Park University ; Northeastern Illinois University ; Robert Morris University Illinois ; Roosevelt University ; Saint Xavier University ; Rush University ; and Shimer College . William Rainey Harper , the first president of the University of Chicago, was instrumental in the creation of the junior college concept, establishing nearby Joliet Junior College as the first in the nation in 1901. His legacy continues with the multiple community colleges in the Chicago proper, including the seven City Colleges of Chicago : Richard J. Daley College , Kennedy–King College , Malcolm X College , Olive–Harvey College , Truman College , Harold Washington College and Wilbur Wright College , in addition to the privately held MacCormac College . [ citation needed ] Chicago also has a high concentration of post-baccalaureate institutions, graduate schools, seminaries, and theological schools, such as the Adler School of Professional Psychology , The Chicago School of Professional Psychology , the Erikson Institute , The Institute for Clinical Social Work , the Lutheran School of Theology at Chicago , the Catholic Theological Union , the Moody Bible Institute , and the University of Chicago Divinity School . [ citation needed ]Chicago Public Schools (CPS) is the governing body of the school district that contains over 600 public elementary and high schools citywide, including several selective-admission magnet schools. There are eleven selective enrollment high schools in the Chicago Public Schools, designed to meet the needs of Chicago's most academically advanced students. These schools offer a rigorous curriculum with mainly honors and Advanced Placement (AP) courses. Walter Payton College Prep High School is ranked number one in the city of Chicago and the state of Illinois. Chicago high school rankings are determined by the average test scores on state achievement tests. The district, with an enrollment exceeding 400,545 students (2013–2014 20th Day Enrollment), is the third-largest in the U.S. On September 10, 2012, teachers for the Chicago Teachers Union went on strike for the first time since 1987 over pay, resources and other issues. According to data compiled in 2014, Chicago's "choice system", where students who test or apply and may attend one of a number of public high schools (there are about 130), sorts students of different achievement levels into different schools (high performing, middle performing, and low performing schools). Chicago has a network of Lutheran schools , and several private schools are run by other denominations and faiths, such as the Ida Crown Jewish Academy in West Ridge . The Roman Catholic Archdiocese of Chicago operates Catholic schools , that include Jesuit preparatory schools and others. A number of private schools are completely secular. There are also the private Chicago Academy for the Arts , a high school focused on six different categories of the arts and the public Chicago High School for the Arts , a high school focused on five categories (visual arts, theatre, musical theatre, dance, and music) of the arts. The Chicago Public Library system operates three regional libraries and 77 neighbourhood branches, including the central library. Since the 1850s, Chicago has been a world center of higher education and research with several universities. These institutions consistently rank among the top "National Universities" in the United States, as determined by U.S. News & World Report . Highly regarded universities in Chicago and the surrounding area are: the University of Chicago; Northwestern University; Illinois Institute of Technology ; Loyola University Chicago ; DePaul University ; Columbia College Chicago and University of Illinois at Chicago. Other notable schools include: Chicago State University ; the School of the Art Institute of Chicago ; East–West University ; National Louis University ; North Park University ; Northeastern Illinois University ; Robert Morris University Illinois ; Roosevelt University ; Saint Xavier University ; Rush University ; and Shimer College . William Rainey Harper , the first president of the University of Chicago, was instrumental in the creation of the junior college concept, establishing nearby Joliet Junior College as the first in the nation in 1901. His legacy continues with the multiple community colleges in the Chicago proper, including the seven City Colleges of Chicago : Richard J. Daley College , Kennedy–King College , Malcolm X College , Olive–Harvey College , Truman College , Harold Washington College and Wilbur Wright College , in addition to the privately held MacCormac College . [ citation needed ] Chicago also has a high concentration of post-baccalaureate institutions, graduate schools, seminaries, and theological schools, such as the Adler School of Professional Psychology , The Chicago School of Professional Psychology , the Erikson Institute , The Institute for Clinical Social Work , the Lutheran School of Theology at Chicago , the Catholic Theological Union , the Moody Bible Institute , and the University of Chicago Divinity School . [ citation needed ]The Chicago metropolitan area is a major media hub and the third-largest media market in the United States, after New York City and Los Angeles. Each of the big four U.S. television networks , CBS , ABC , NBC and Fox , directly owns and operates a high-definition television station in Chicago ( WBBM 2, WLS 7, WMAQ 5 and WFLD 32, respectively). Former CW affiliate WGN-TV 9, which was owned from its inception by Tribune Broadcasting (now owned by the Nexstar Media Group since 2019), is carried with some programming differences, as " WGN America " on cable and satellite TV nationwide and in parts of the Caribbean . WGN America eventually became NewsNation in 2021. Chicago has also been the home of several prominent talk shows, including The Oprah Winfrey Show , Steve Harvey Show , The Rosie Show , The Jerry Springer Show , The Phil Donahue Show , The Jenny Jones Show , and more. The city also has one PBS member station (its second: WYCC 20, removed its affiliation with PBS in 2017 ): WTTW 11, producer of shows such as Sneak Previews , The Frugal Gourmet , Lamb Chop's Play-Along and The McLaughlin Group . As of 2018 [ update ] , Windy City Live is Chicago's only daytime talk show, which is hosted by Val Warner and Ryan Chiaverini at ABC7 Studios with a live weekday audience. Since 1999, Judge Mathis also films his syndicated arbitration-based reality court show at the NBC Tower . Beginning in January 2019, Newsy began producing 12 of its 14 hours of live news programming per day from its new facility in Chicago. [ citation needed ] Most of Chicago's television stations are owned and operated by the big television network companies. They are: Two major daily newspapers are published in Chicago: the Chicago Tribune and the Chicago Sun-Times , with the Tribune having the larger circulation. There are also several regional and special-interest newspapers and magazines, such as Chicago , the Dziennik ZwiÄ zkowy ( Polish Daily News ) , Draugas (the Lithuanian daily newspaper), the Chicago Reader , the SouthtownStar , the Chicago Defender , the Daily Herald , Newcity , StreetWise and the Windy City Times . The entertainment and cultural magazine Time Out Chicago and GRAB magazine are also published in the city, as well as local music magazine Chicago Innerview . In addition, Chicago is the home of satirical national news outlet, The Onion , as well as its sister pop-culture publication, The A.V. Club . Chicago has five 50,000 watt AM radio stations : the Audacy -owned WBBM and WSCR ; the Tribune Broadcasting -owned WGN ; the Cumulus Media -owned WLS ; and the ESPN Radio -owned WMVP . Chicago is also home to a number of national radio shows, including Beyond the Beltway with Bruce DuMont on Sunday evenings. [ citation needed ] Chicago Public Radio produces nationally aired programs such as PRI 's This American Life and NPR 's Wait Wait...Don't Tell Me! . [ citation needed ]The Chicago metropolitan area is a major media hub and the third-largest media market in the United States, after New York City and Los Angeles. Each of the big four U.S. television networks , CBS , ABC , NBC and Fox , directly owns and operates a high-definition television station in Chicago ( WBBM 2, WLS 7, WMAQ 5 and WFLD 32, respectively). Former CW affiliate WGN-TV 9, which was owned from its inception by Tribune Broadcasting (now owned by the Nexstar Media Group since 2019), is carried with some programming differences, as " WGN America " on cable and satellite TV nationwide and in parts of the Caribbean . WGN America eventually became NewsNation in 2021. Chicago has also been the home of several prominent talk shows, including The Oprah Winfrey Show , Steve Harvey Show , The Rosie Show , The Jerry Springer Show , The Phil Donahue Show , The Jenny Jones Show , and more. The city also has one PBS member station (its second: WYCC 20, removed its affiliation with PBS in 2017 ): WTTW 11, producer of shows such as Sneak Previews , The Frugal Gourmet , Lamb Chop's Play-Along and The McLaughlin Group . As of 2018 [ update ] , Windy City Live is Chicago's only daytime talk show, which is hosted by Val Warner and Ryan Chiaverini at ABC7 Studios with a live weekday audience. Since 1999, Judge Mathis also films his syndicated arbitration-based reality court show at the NBC Tower . Beginning in January 2019, Newsy began producing 12 of its 14 hours of live news programming per day from its new facility in Chicago. [ citation needed ] Most of Chicago's television stations are owned and operated by the big television network companies. They are:Most of Chicago's television stations are owned and operated by the big television network companies. They are:Two major daily newspapers are published in Chicago: the Chicago Tribune and the Chicago Sun-Times , with the Tribune having the larger circulation. There are also several regional and special-interest newspapers and magazines, such as Chicago , the Dziennik ZwiÄ zkowy ( Polish Daily News ) , Draugas (the Lithuanian daily newspaper), the Chicago Reader , the SouthtownStar , the Chicago Defender , the Daily Herald , Newcity , StreetWise and the Windy City Times . The entertainment and cultural magazine Time Out Chicago and GRAB magazine are also published in the city, as well as local music magazine Chicago Innerview . In addition, Chicago is the home of satirical national news outlet, The Onion , as well as its sister pop-culture publication, The A.V. Club . Chicago has five 50,000 watt AM radio stations : the Audacy -owned WBBM and WSCR ; the Tribune Broadcasting -owned WGN ; the Cumulus Media -owned WLS ; and the ESPN Radio -owned WMVP . Chicago is also home to a number of national radio shows, including Beyond the Beltway with Bruce DuMont on Sunday evenings. [ citation needed ] Chicago Public Radio produces nationally aired programs such as PRI 's This American Life and NPR 's Wait Wait...Don't Tell Me! . [ citation needed ]Chicago is a major transportation hub in the United States. It is an important component in global distribution, as it is the third-largest inter-modal port in the world after Hong Kong and Singapore . The city of Chicago has a higher than average percentage of households without a car. In 2015, 26.5 percent of Chicago households were without a car, and increased slightly to 27.5 percent in 2016. The national average was 8.7 percent in 2016. Chicago averaged 1.12 cars per household in 2016, compared to a national average of 1.8. Due to Chicago's Wheel Tax , residents of Chicago who own a vehicle are required to purchase a Chicago City Vehicle Sticker. In established Residential Parking Zones, only local residents can purchase Zone-specific parking stickers for themselves and guests. Chicago since 2009 has relinquished rights to its public street parking. In 2008, as Chicago struggled to close a growing budget deficit, the city agreed to a 75-year, $1.16 billion deal to lease its parking meter system to an operating company created by Morgan Stanley , called Chicago Parking Meters LLC . Daley said the "agreement is very good news for the taxpayers of Chicago because it will provide more than $1 billion in net proceeds that can be used during this very difficult economy." The rights of the parking ticket lease end in 2081, and since 2022 have already recouped over $1.5 billion in revenue for Chicago Parking Meters LLC investors. Seven mainline and four auxiliary interstate highways ( 55 , 57 , 65 (only in Indiana), 80 (also in Indiana ), 88 , 90 (also in Indiana ), 94 (also in Indiana ), 190 , 290 , 294 , and 355 ) run through Chicago and its suburbs. Segments that link to the city center are named after influential politicians, with three of them named after former U.S. Presidents (Eisenhower, Kennedy, and Reagan) and one named after two-time Democratic candidate Adlai Stevenson . The Kennedy and Dan Ryan Expressways are the busiest state maintained routes in the entire state of Illinois. The Regional Transportation Authority (RTA) coordinates the operation of the three service boards: CTA, Metra, and Pace. Greyhound Lines provides inter-city bus service to and from the city at the Chicago Bus Station , and Chicago is also the hub for the Midwest network of Megabus (North America) . Amtrak long distance and commuter rail services originate from Union Station . Chicago is one of the largest hubs of passenger rail service in the nation. The services terminate in the San Francisco area, Washington, D.C., New York City, New Orleans, Portland , Seattle , Milwaukee , Quincy , St. Louis , Carbondale , Boston, Grand Rapids , Port Huron , Pontiac , Los Angeles, and San Antonio . Future services will terminate at Rockford and Moline . An attempt was made in the early 20th century to link Chicago with New York City via the Chicago – New York Electric Air Line Railroad . Parts of this were built, but it was never completed. In July 2013, the bicycle-sharing system Divvy was launched with 750 bikes and 75 docking stations It is operated by Lyft for the Chicago Department of Transportation . As of July 2019, Divvy operated 5800 bicycles at 608 stations, covering almost all of the city, excluding Pullman , Rosedale, Beverly , Belmont Cragin and Edison Park . In May 2019, The City of Chicago announced its Chicago's Electric Shared Scooter Pilot Program, scheduled to run from June 15 to October 15. The program started on June 15 with 10 different scooter companies, including scooter sharing market leaders Bird , Jump , Lime and Lyft . Each company was allowed to bring 250 electric scooters , although both Bird and Lime claimed that they experienced a higher demand for their scooters. The program ended on October 15, with nearly 800,000 rides taken. Chicago is the largest hub in the railroad industry. All five Class I railroads meet in Chicago. As of 2002 [ update ] , severe freight train congestion caused trains to take as long to get through the Chicago region as it took to get there from the West Coast of the country (about 2 days). According to U.S. Department of Transportation, the volume of imported and exported goods transported via rail to, from, or through Chicago is forecast to increase nearly 150 percent between 2010 and 2040. CREATE, the Chicago Region Environmental and Transportation Efficiency Program , comprises about 70 programs, including crossovers, overpasses and underpasses, that intend to significantly improve the speed of freight movements in the Chicago area. Chicago is served by O'Hare International Airport , the world's busiest airport measured by airline operations, on the far Northwest Side, and Midway International Airport on the Southwest Side. In 2005, O'Hare was the world's busiest airport by aircraft movements and the second-busiest by total passenger traffic. Both O'Hare and Midway are owned and operated by the City of Chicago. Gary/Chicago International Airport and Chicago Rockford International Airport , located in Gary, Indiana and Rockford, Illinois , respectively, can serve as alternative Chicago area airports, however they do not offer as many commercial flights as O'Hare and Midway. In recent years the state of Illinois has been leaning towards building an entirely new airport in the Illinois suburbs of Chicago. The City of Chicago is the world headquarters for United Airlines , the world's third-largest airline. The Port of Chicago consists of several major port facilities within the city of Chicago operated by the Illinois International Port District (formerly known as the Chicago Regional Port District). The central element of the Port District, Calumet Harbor, is maintained by the U.S. Army Corps of Engineers . Electricity for most of northern Illinois is provided by Commonwealth Edison , also known as ComEd. Their service territory borders Iroquois County to the south, the Wisconsin border to the north, the Iowa border to the west and the Indiana border to the east. In northern Illinois, ComEd (a division of Exelon ) operates the greatest number of nuclear generating plants in any U.S. state. Because of this, ComEd reports indicate that Chicago receives about 75% of its electricity from nuclear power. Recently, the city began installing wind turbines on government buildings to promote renewable energy. Natural gas is provided by Peoples Gas, a subsidiary of Integrys Energy Group , which is headquartered in Chicago. Domestic and industrial waste was once incinerated but it is now landfilled , mainly in the Calumet area . From 1995 to 2008, the city had a blue bag program to divert recyclable refuse from landfills. Because of low participation in the blue bag programs, the city began a pilot program for blue bin recycling like other cities. This proved successful and blue bins were rolled out across the city. The Illinois Medical District is on the Near West Side. It includes Rush University Medical Center , ranked as the second best hospital in the Chicago metropolitan area by U.S. News & World Report for 2014–16, the University of Illinois Medical Center at Chicago , Jesse Brown VA Hospital, and John H. Stroger Jr. Hospital of Cook County , one of the busiest trauma centers in the nation. Two of the country's premier academic medical centers reside in Chicago, including Northwestern Memorial Hospital and the University of Chicago Medical Center . The Chicago campus of Northwestern University includes the Feinberg School of Medicine ; Northwestern Memorial Hospital, which is ranked as the best hospital in the Chicago metropolitan area by U.S. News & World Report for 2017–18; the Shirley Ryan AbilityLab (formerly named the Rehabilitation Institute of Chicago), which is ranked the best U.S. rehabilitation hospital by U.S. News & World Report ; the new Prentice Women's Hospital ; and Ann & Robert H. Lurie Children's Hospital of Chicago. The University of Illinois College of Medicine at UIC is the second largest medical school in the United States (2,600 students including those at campuses in Peoria, Rockford and Urbana–Champaign ). In addition, the Chicago Medical School and Loyola University Chicago's Stritch School of Medicine are located in the suburbs of North Chicago and Maywood , respectively. The Midwestern University Chicago College of Osteopathic Medicine is in Downers Grove . The American Medical Association , Accreditation Council for Graduate Medical Education , Accreditation Council for Continuing Medical Education , American Osteopathic Association , American Dental Association , Academy of General Dentistry , Academy of Nutrition and Dietetics , American Association of Nurse Anesthetists , American College of Surgeons , American Society for Clinical Pathology , American College of Healthcare Executives, the American Hospital Association and Blue Cross and Blue Shield Association are all based in Chicago.Chicago is a major transportation hub in the United States. It is an important component in global distribution, as it is the third-largest inter-modal port in the world after Hong Kong and Singapore . The city of Chicago has a higher than average percentage of households without a car. In 2015, 26.5 percent of Chicago households were without a car, and increased slightly to 27.5 percent in 2016. The national average was 8.7 percent in 2016. Chicago averaged 1.12 cars per household in 2016, compared to a national average of 1.8. Due to Chicago's Wheel Tax , residents of Chicago who own a vehicle are required to purchase a Chicago City Vehicle Sticker. In established Residential Parking Zones, only local residents can purchase Zone-specific parking stickers for themselves and guests. Chicago since 2009 has relinquished rights to its public street parking. In 2008, as Chicago struggled to close a growing budget deficit, the city agreed to a 75-year, $1.16 billion deal to lease its parking meter system to an operating company created by Morgan Stanley , called Chicago Parking Meters LLC . Daley said the "agreement is very good news for the taxpayers of Chicago because it will provide more than $1 billion in net proceeds that can be used during this very difficult economy." The rights of the parking ticket lease end in 2081, and since 2022 have already recouped over $1.5 billion in revenue for Chicago Parking Meters LLC investors. Seven mainline and four auxiliary interstate highways ( 55 , 57 , 65 (only in Indiana), 80 (also in Indiana ), 88 , 90 (also in Indiana ), 94 (also in Indiana ), 190 , 290 , 294 , and 355 ) run through Chicago and its suburbs. Segments that link to the city center are named after influential politicians, with three of them named after former U.S. Presidents (Eisenhower, Kennedy, and Reagan) and one named after two-time Democratic candidate Adlai Stevenson . The Kennedy and Dan Ryan Expressways are the busiest state maintained routes in the entire state of Illinois. The Regional Transportation Authority (RTA) coordinates the operation of the three service boards: CTA, Metra, and Pace. Greyhound Lines provides inter-city bus service to and from the city at the Chicago Bus Station , and Chicago is also the hub for the Midwest network of Megabus (North America) . Amtrak long distance and commuter rail services originate from Union Station . Chicago is one of the largest hubs of passenger rail service in the nation. The services terminate in the San Francisco area, Washington, D.C., New York City, New Orleans, Portland , Seattle , Milwaukee , Quincy , St. Louis , Carbondale , Boston, Grand Rapids , Port Huron , Pontiac , Los Angeles, and San Antonio . Future services will terminate at Rockford and Moline . An attempt was made in the early 20th century to link Chicago with New York City via the Chicago – New York Electric Air Line Railroad . Parts of this were built, but it was never completed. In July 2013, the bicycle-sharing system Divvy was launched with 750 bikes and 75 docking stations It is operated by Lyft for the Chicago Department of Transportation . As of July 2019, Divvy operated 5800 bicycles at 608 stations, covering almost all of the city, excluding Pullman , Rosedale, Beverly , Belmont Cragin and Edison Park . In May 2019, The City of Chicago announced its Chicago's Electric Shared Scooter Pilot Program, scheduled to run from June 15 to October 15. The program started on June 15 with 10 different scooter companies, including scooter sharing market leaders Bird , Jump , Lime and Lyft . Each company was allowed to bring 250 electric scooters , although both Bird and Lime claimed that they experienced a higher demand for their scooters. The program ended on October 15, with nearly 800,000 rides taken. Chicago is the largest hub in the railroad industry. All five Class I railroads meet in Chicago. As of 2002 [ update ] , severe freight train congestion caused trains to take as long to get through the Chicago region as it took to get there from the West Coast of the country (about 2 days). According to U.S. Department of Transportation, the volume of imported and exported goods transported via rail to, from, or through Chicago is forecast to increase nearly 150 percent between 2010 and 2040. CREATE, the Chicago Region Environmental and Transportation Efficiency Program , comprises about 70 programs, including crossovers, overpasses and underpasses, that intend to significantly improve the speed of freight movements in the Chicago area. Chicago is served by O'Hare International Airport , the world's busiest airport measured by airline operations, on the far Northwest Side, and Midway International Airport on the Southwest Side. In 2005, O'Hare was the world's busiest airport by aircraft movements and the second-busiest by total passenger traffic. Both O'Hare and Midway are owned and operated by the City of Chicago. Gary/Chicago International Airport and Chicago Rockford International Airport , located in Gary, Indiana and Rockford, Illinois , respectively, can serve as alternative Chicago area airports, however they do not offer as many commercial flights as O'Hare and Midway. In recent years the state of Illinois has been leaning towards building an entirely new airport in the Illinois suburbs of Chicago. The City of Chicago is the world headquarters for United Airlines , the world's third-largest airline. The Port of Chicago consists of several major port facilities within the city of Chicago operated by the Illinois International Port District (formerly known as the Chicago Regional Port District). The central element of the Port District, Calumet Harbor, is maintained by the U.S. Army Corps of Engineers . Due to Chicago's Wheel Tax , residents of Chicago who own a vehicle are required to purchase a Chicago City Vehicle Sticker. In established Residential Parking Zones, only local residents can purchase Zone-specific parking stickers for themselves and guests. Chicago since 2009 has relinquished rights to its public street parking. In 2008, as Chicago struggled to close a growing budget deficit, the city agreed to a 75-year, $1.16 billion deal to lease its parking meter system to an operating company created by Morgan Stanley , called Chicago Parking Meters LLC . Daley said the "agreement is very good news for the taxpayers of Chicago because it will provide more than $1 billion in net proceeds that can be used during this very difficult economy." The rights of the parking ticket lease end in 2081, and since 2022 have already recouped over $1.5 billion in revenue for Chicago Parking Meters LLC investors. Seven mainline and four auxiliary interstate highways ( 55 , 57 , 65 (only in Indiana), 80 (also in Indiana ), 88 , 90 (also in Indiana ), 94 (also in Indiana ), 190 , 290 , 294 , and 355 ) run through Chicago and its suburbs. Segments that link to the city center are named after influential politicians, with three of them named after former U.S. Presidents (Eisenhower, Kennedy, and Reagan) and one named after two-time Democratic candidate Adlai Stevenson . The Kennedy and Dan Ryan Expressways are the busiest state maintained routes in the entire state of Illinois. The Regional Transportation Authority (RTA) coordinates the operation of the three service boards: CTA, Metra, and Pace. Greyhound Lines provides inter-city bus service to and from the city at the Chicago Bus Station , and Chicago is also the hub for the Midwest network of Megabus (North America) .Amtrak long distance and commuter rail services originate from Union Station . Chicago is one of the largest hubs of passenger rail service in the nation. The services terminate in the San Francisco area, Washington, D.C., New York City, New Orleans, Portland , Seattle , Milwaukee , Quincy , St. Louis , Carbondale , Boston, Grand Rapids , Port Huron , Pontiac , Los Angeles, and San Antonio . Future services will terminate at Rockford and Moline . An attempt was made in the early 20th century to link Chicago with New York City via the Chicago – New York Electric Air Line Railroad . Parts of this were built, but it was never completed.In July 2013, the bicycle-sharing system Divvy was launched with 750 bikes and 75 docking stations It is operated by Lyft for the Chicago Department of Transportation . As of July 2019, Divvy operated 5800 bicycles at 608 stations, covering almost all of the city, excluding Pullman , Rosedale, Beverly , Belmont Cragin and Edison Park . In May 2019, The City of Chicago announced its Chicago's Electric Shared Scooter Pilot Program, scheduled to run from June 15 to October 15. The program started on June 15 with 10 different scooter companies, including scooter sharing market leaders Bird , Jump , Lime and Lyft . Each company was allowed to bring 250 electric scooters , although both Bird and Lime claimed that they experienced a higher demand for their scooters. The program ended on October 15, with nearly 800,000 rides taken. Chicago is the largest hub in the railroad industry. All five Class I railroads meet in Chicago. As of 2002 [ update ] , severe freight train congestion caused trains to take as long to get through the Chicago region as it took to get there from the West Coast of the country (about 2 days). According to U.S. Department of Transportation, the volume of imported and exported goods transported via rail to, from, or through Chicago is forecast to increase nearly 150 percent between 2010 and 2040. CREATE, the Chicago Region Environmental and Transportation Efficiency Program , comprises about 70 programs, including crossovers, overpasses and underpasses, that intend to significantly improve the speed of freight movements in the Chicago area. Chicago is served by O'Hare International Airport , the world's busiest airport measured by airline operations, on the far Northwest Side, and Midway International Airport on the Southwest Side. In 2005, O'Hare was the world's busiest airport by aircraft movements and the second-busiest by total passenger traffic. Both O'Hare and Midway are owned and operated by the City of Chicago. Gary/Chicago International Airport and Chicago Rockford International Airport , located in Gary, Indiana and Rockford, Illinois , respectively, can serve as alternative Chicago area airports, however they do not offer as many commercial flights as O'Hare and Midway. In recent years the state of Illinois has been leaning towards building an entirely new airport in the Illinois suburbs of Chicago. The City of Chicago is the world headquarters for United Airlines , the world's third-largest airline.The Port of Chicago consists of several major port facilities within the city of Chicago operated by the Illinois International Port District (formerly known as the Chicago Regional Port District). The central element of the Port District, Calumet Harbor, is maintained by the U.S. Army Corps of Engineers . Electricity for most of northern Illinois is provided by Commonwealth Edison , also known as ComEd. Their service territory borders Iroquois County to the south, the Wisconsin border to the north, the Iowa border to the west and the Indiana border to the east. In northern Illinois, ComEd (a division of Exelon ) operates the greatest number of nuclear generating plants in any U.S. state. Because of this, ComEd reports indicate that Chicago receives about 75% of its electricity from nuclear power. Recently, the city began installing wind turbines on government buildings to promote renewable energy. Natural gas is provided by Peoples Gas, a subsidiary of Integrys Energy Group , which is headquartered in Chicago. Domestic and industrial waste was once incinerated but it is now landfilled , mainly in the Calumet area . From 1995 to 2008, the city had a blue bag program to divert recyclable refuse from landfills. Because of low participation in the blue bag programs, the city began a pilot program for blue bin recycling like other cities. This proved successful and blue bins were rolled out across the city. The Illinois Medical District is on the Near West Side. It includes Rush University Medical Center , ranked as the second best hospital in the Chicago metropolitan area by U.S. News & World Report for 2014–16, the University of Illinois Medical Center at Chicago , Jesse Brown VA Hospital, and John H. Stroger Jr. Hospital of Cook County , one of the busiest trauma centers in the nation. Two of the country's premier academic medical centers reside in Chicago, including Northwestern Memorial Hospital and the University of Chicago Medical Center . The Chicago campus of Northwestern University includes the Feinberg School of Medicine ; Northwestern Memorial Hospital, which is ranked as the best hospital in the Chicago metropolitan area by U.S. News & World Report for 2017–18; the Shirley Ryan AbilityLab (formerly named the Rehabilitation Institute of Chicago), which is ranked the best U.S. rehabilitation hospital by U.S. News & World Report ; the new Prentice Women's Hospital ; and Ann & Robert H. Lurie Children's Hospital of Chicago. The University of Illinois College of Medicine at UIC is the second largest medical school in the United States (2,600 students including those at campuses in Peoria, Rockford and Urbana–Champaign ). In addition, the Chicago Medical School and Loyola University Chicago's Stritch School of Medicine are located in the suburbs of North Chicago and Maywood , respectively. The Midwestern University Chicago College of Osteopathic Medicine is in Downers Grove . The American Medical Association , Accreditation Council for Graduate Medical Education , Accreditation Council for Continuing Medical Education , American Osteopathic Association , American Dental Association , Academy of General Dentistry , Academy of Nutrition and Dietetics , American Association of Nurse Anesthetists , American College of Surgeons , American Society for Clinical Pathology , American College of Healthcare Executives, the American Hospital Association and Blue Cross and Blue Shield Association are all based in Chicago.

Wiki

Cholera

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

United Nations Stabilisation Mission in Haiti

The United Nations Stabilisation Mission in Haiti ( French : Mission des Nations Unies pour la stabilisation en Haïti ), also known as MINUSTAH , an acronym of the French name, was a UN peacekeeping mission in Haiti that was in operation from 2004 to 2017. The mission's military component was led by the Brazilian Army and commanded by a Brazilian. The force was composed of 2,366 military personnel and 2,533 police, supported by international civilian personnel, a local civilian staff and United Nations Volunteers. The devastating January 2010 Haiti earthquake caused the collapse of the mission's headquarters in Port-au-Prince and killed the mission's chief, Hédi Annabi of Tunisia , his deputy Luiz Carlos da Costa of Brazil , and the acting police commissioner, RCMP Supt. Doug Coates of Canada . On 14 January 2010, UN headquarters dispatched the former head of MINUSTAH and current Assistant Secretary-General for Peacekeeping Operations, Edmond Mulet , as the organisation's Acting Special Representative of the Secretary-General and interim head of MINUSTAH. Following the earthquake, MINUSTAH concentrated on assisting the Haitian National Police in providing security within the country, while American and Canadian military forces distributed humanitarian aid and provided security for aid distribution. Due to fears of instability, United Nations Security Council Resolution 1944 extended MINUSTAH's mandate, and it was periodically renewed until 2017. On 13 April 2017, the United Nations Security Council announced that the mission would end in October 2017. It was replaced by a much smaller follow-up mission, the United Nations Mission for Justice Support in Haiti (MINUJUSTH), which itself concluded in 2019.According to its mandate from the UN Security Council , MINUSTAH was required to concentrate the use of its resources, including civilian police, on increasing security and protection during the electoral period and to assist with the restoration and maintenance of the rule of law, public safety and public order in Haiti. MINUSTAH was established by United Nations Security Council Resolution 1542 on 30 April 2004 because the Security Council deemed the situation in Haiti to be a threat to international peace and security in the region. In 2004, UN peacekeepers entered Cité Soleil in an attempt to gain control of the area and end the anarchy. In 2004, independent human rights organizations accused the Haitian National Police (HNP) and sometimes MINUSTAH of atrocities against civilians. It is still argued if any, or how many civilians were killed as a by-product of MINUSTAH crackdowns on criminals operating from slums. The UN and MINUSTAH expressed deep regret for any loss of life during operations. In early 2005, MINUSTAH force commander Lieutenant-General Augusto Heleno Ribeiro Pereira testified at a congressional commission in Brazil that "we are under extreme pressure from the international community to use violence", citing Canada, France, and the United States. Having ended his tour of duty, on 1 September 2005, Heleno was replaced by General Urano Teixeira da Matta Bacellar as force commander of MINUSTAH. On 7 January 2006, Bacellar was found dead in his hotel room. The death was considered to be suicide, however later some suspicion of assassination arose. His interim replacement was Chilean General Eduardo Aldunate Hermann. On 17 January 2006, it was announced that Brazilian General José Elito Carvalho Siqueira would be the permanent replacement for Bacellar as the head of the United Nations' Haiti force. On 14 February 2006, in its Resolution 1658 , the United Nations Security Council extended MINUSTAH's mandate until 15 August 2006. MINUSTAH is also a precedent as the first mission in the region to be led by the Brazilian and Chilean military, and almost entirely composed of, Latin American forces, particularly from Brazil , Argentina , Chile , Bolivia , Ecuador and Uruguay . From 1 September 2007 until his death following the earthquake on 12 January 2010 , the mission was led by Tunisian Hédi Annabi . India provided three units of around 500 police personnel for MINUSTAH. The Indian contingent joined the mission in October 2008, and were stationed in Port-au-Prince and Hinche. They were tasked with maintaining law and order, setting up and operating checkpoints, and anti-crime operations. Two Indian police units remained in Haiti after MINUSTAH ended on 15 October 2017, to serve in the successor mission, the United Nations Mission for Justice Support in Haiti (MINUJUSTH). On 23 February 2004, the United Nations Security Council was convened at the request of CARICOM for the first time in four years to address the deteriorating situation in Haiti. On 29 February 2004, the Security Council passed a resolution "taking note of the resignation of Jean-Bertrand Aristide as President of Haiti and the swearing-in of President Boniface Alexandre as the acting President of Haiti in accordance with the Constitution of Haiti" and authorized the immediate deployment of a Multinational Interim Force. On 30 April 2004, MINUSTAH was established and given its mandate with a military component of up to 6,700 troops. In July, the General Assembly authorized the financing of the mission with US$200 million which followed a donors' conference in Washington DC. The first progress report from MINUSTAH was released at the end of August. In September the interim president of Haiti, Boniface Alexandre, spoke to the United Nations General Assembly in support of MINUSTAH. In November there was a second report, and the Security Council mandate for MINUSTAH. The mandate has most recently been extended by the Security Council until October 2010 "with the intention of further renewal". Although the United Nations Stabilization Mission (MINUSTAH) had been in Haiti since 2004, as of 2007, it continued to struggle for control over the armed gangs. It maintained an armed checkpoint at the entrance to the shanty town of Cité Soleil and a roadblock with armed vehicles. In January 2006, two Jordanian peacekeepers were killed in Cité Soleil. In October 2006, a heavily armed group of the Haitian National Police were able to enter Cité Soleil for the first time in three years and were able to remain one hour as armoured UN troops patrolled the area. Since this is where the armed gangs take their kidnap victims, the police's ability to penetrate the area even for such a short time was seen as a sign of progress. The situation of continuing violence is similar in Port-au-Prince . Ex-soldiers, supporters of the ex-president, occupied the home of ex-president Jean-Bertrand Aristide against the wishes of the Haitian government. Before Christmas 2006, the UN force announced that it would take a tougher stance against gang members in Port-au-Prince. However, since then, the atmosphere there has not improved and the armed roadblocks and barbed wire barricades have not been moved. After four people were killed and another six injured in a UN operation exchange of fire with criminals in Cité Soleil in late January 2007, the United States announced that it would contribute $20 million to create jobs in Cité Soleil. In early February 2007, 700 UN troops flooded Cité Soleil, which led to a major gun battle. Although the troops make regular forcible entries into the area, a spokesperson said this one was the largest attempted so far by the UN troops. On 28 July 2007, Edmond Mulet , the UN Special Representative in Haiti and MINUSTAH Mission Chief, warned of a sharp increase in lynchings and other mob attacks in Haiti. He said MINUSTAH, which now has 9,000 troops there, will launch a campaign to remind people that lynchings are a crime. On 2 August 2007, UN Secretary-General Ban Ki-moon arrived in Haiti to assess the role of the UN forces, announcing that he would visit Cité Soleil during his visit. He said that it was Haiti's largest slum and, as such, was the most important target for U.N. peacekeepers in gaining control over the armed gangs. During his visit, he announced an extension of the mandate of the UN forces in Haiti. It took MINUSTAH three months and 800 arrests to deal with the gangs and decrease the number of kidnappings on the streets. President René Préval has expressed ambivalent feelings about the UN security presence, stating that "if the Haitian people were asked if they wanted the UN forces to leave they would say yes." Survivors frequently blame the UN peacekeepers for deaths of relatives. In April 2008, Haiti was facing a severe food crisis as well as governmental destabilization to Parliament's failure to ratify the president's choice of a prime minister. There were severe riots, so the UN force fired rubber bullets in Port-au-Prince and the riot calmed. The head of MINUSTAH called for a new government to be chosen as soon as possible. Meanwhile, the UN provided emergency food. Haiti was hit by four consecutive hurricanes between August and September 2008. These storms crippled coastal regions, requiring humanitarian aid for 800,000 people. Critics of MINUSTAH's goal of providing security said that the provision of increased police presence came with the unfortunate consequence of neglecting the vast socioeconomic problems in the area, the lack of effort in addressing infrastructure improvement, the joblessness, and the pervasive poverty. In 2009, with the appointment of former U.S. President Bill Clinton as the UN Special Envoy, there was hope that the international donor community would provide increased aid. MINUSTAH renewed its commitment to Haiti, and $3 billion for projects was pledged by the international community, mainly for rebuilding after the hurricanes. However, in Cité Soleil, there were signs of a desire for political independence from the efforts of the international community. In October 2010, nine months after the earthquake, the UN extended MINUSTAH's mission. In the capital, there were protests from those who want the MINUSTAH to leave. Demonstrators chanted "Down with the occupation" and burned the flag of Brazil , as representative of the largest contingent of MINUSTAH. On 12 January 2010, the United Nations reported that headquarters of the United Nations Stabilization Mission in Haiti (MINUSTAH), the Christopher Hotel in Port-au-Prince, collapsed, and several other UN facilities were damaged; a large number of UN personnel were unaccounted for in the aftermath of a major earthquake . The Mission's Chief, Hédi Annabi , was reported dead on 13 January by President René Préval and French news sources, and on 16 January, the United Nations confirmed the death after his body was recovered by a search and rescue team from China . Principal Deputy Special Representative Luiz Carlos da Costa was also confirmed dead, as well as the Acting Police Commissioner, Royal Canadian Mounted Police (RCMP) Superintendent Doug Coates, who were meeting with eight Chinese nationals—four peacekeepers and a delegation of four police officers from China—when the earthquake struck. The Chinese search and rescue team recovered the bodies of the ten individuals on 16 January 2010. Jens Kristensen, senior humanitarian officer for the UN, was rescued by a team from the state of Virginia after five days trapped in the rubble. In October 2010, a cholera outbreak was confirmed in Haiti—the first in the country's modern history. According to the Centers for Disease Control and Prevention (CDC), as of 4 August 2013, over 800,000 cases and 9,600 deaths had been reported since the outbreak first began in October 2010. MINUSTAH was linked with introducing the disease to the country by sources such as the CDC, the American Society for Microbiology, Yale Law School and the School of Public Health. The cause of the disease was attributed to faulty construction of UN sanitation systems in its base located in the town of Méyè . Many reports from Méyè stated that people had seen sewage spilling from the UN base into the Artibonite River , the largest river in Haiti, and which is used by residents for drinking, cooking, and bathing. In December 2010, a study traced the Haitian cholera strain to South Asia . The UN conducted an independent investigation into the origin of the epidemic at the end of 2010. A panel of independent UN experts was assembled and their collective findings were compiled in a report. The panel determined that the evidence implicating the Nepalese troops was inconclusive. Though they admitted that the cholera strain was most likely from Nepal, it cited a confluence of factors that also contributed to the outbreak and that no one "deliberate action of, a group or individual was to blame". However, in 2013, the committee changed its statement concluding that the UN troops from Nepal "most likely" were the cause of the outbreak. The Bureau des Avocats Internationaux (BAI), a Haitian coalition of lawyers, and the Institute for Justice & Democracy in Haiti (IJDH), its U.S. affiliate, filed claims with MINUSTAH on behalf of 5,000 Haitian petitioners in November 2011. The claims asked for the installation of the water and sanitation infrastructure necessary to control the epidemic, compensation for the victims, and an apology. Fifteen months later, in February 2013, the UN stated that the case was "not receivable," because it involved "review of policy matters", citing the Convention on Privileges and Immunities of the United Nations . In October 2013, BAI, IJDH, and another U.S. law firm filed a lawsuit challenging UN immunity in U.S. federal court on behalf of Haitian and Haitian-American victims of the cholera epidemic. In January 2015, Judge J. Paul Oetken of the U.S. District Court in Manhattan dismissed the lawsuit, affirming UN immunity. In May 2015, an appeal to Oetken's decision was filed. In February 2013, the Haitian government created its National Plan for the Elimination of Cholera, a 10-year plan set to eradicate the disease. Two of the ten years will be devoted as a short-term response to the epidemic. The last eight will be to completely eliminate the disease. The projected budget for the plan is $2 billion. To support the initiative, UN Secretary-General Ban Ki-moon pledged $23.5 million to combat cholera. However, following the pledge, there was much discontent with the UN's progress. 19 members of the U.S. Congress urged the UN to take responsibility for cholera in Haiti. In two separate occasions, members of the US Congress sent a letter to the US ambassador to the UN, Susan Rice , urging her and the organization to ensure that the cholera initiative was fully funded and implemented quickly. Nineteen US Representatives also wrote to Ban Ki-Moon to express concerns about the seeming lack of progress in the UN's cholera response. Ban Ki-moon told members of the US Congress that the UN was committed in helping Haiti overcome the epidemic though no financial compensation to the victims would be granted. Since 2010, the UN has spent and/or committed more than $140 million to the epidemic. On 9 May 2013, the Haitian Senate unanimously voted—save for one abstention—on a policy that would demand the UN to compensate the nation's cholera victims. The Senators also proposed to form "a commission of experts in international and penal law to study what legal means, both nationally and internationally, could be used to prove MINUSTAH's responsibility for starting the cholera outbreak." In August 2016, a report written by UN special rapporteur Philip Alston was leaked to the New York Times . Alston issued a scathing condemnation of the UN's legal approach to cholera in Haiti, which he termed "morally unconscionable, legally indefensible and politically self-defeating." Alston also lamented that the UN's approach "upholds a double standard according to which the U.N. insists that member states respect human rights, while rejecting any such responsibility for itself." Four months later, Secretary-General Ban Ki-moon issued an apology for the UN's role in the cholera outbreak and stressed the organization's "moral responsibility" to fight the disease. Though the apology stopped short of admitting fault for introducing the disease to Haiti, many victim advocates saw it as a major milestone. Ban also launched "a new approach" to cholera by the UN, in the form of a two-track plan. The UN would raise $400 million in voluntary contributions from member states, with $200 million dedicated to providing material assistance to communities most affected by cholera, and another $200 million going to fight the disease. However, the plan gained little traction among member states. Because remaining funds allocated to MINUSTAH were not required to be repurposed for cholera reparations, many member states took back their contributions, and by July 2017 just $9.22 million had been raised. In August 2016, a report written by UN special rapporteur Philip Alston was leaked to the New York Times . Alston issued a scathing condemnation of the UN's legal approach to cholera in Haiti, which he termed "morally unconscionable, legally indefensible and politically self-defeating." Alston also lamented that the UN's approach "upholds a double standard according to which the U.N. insists that member states respect human rights, while rejecting any such responsibility for itself." Four months later, Secretary-General Ban Ki-moon issued an apology for the UN's role in the cholera outbreak and stressed the organization's "moral responsibility" to fight the disease. Though the apology stopped short of admitting fault for introducing the disease to Haiti, many victim advocates saw it as a major milestone. Ban also launched "a new approach" to cholera by the UN, in the form of a two-track plan. The UN would raise $400 million in voluntary contributions from member states, with $200 million dedicated to providing material assistance to communities most affected by cholera, and another $200 million going to fight the disease. However, the plan gained little traction among member states. Because remaining funds allocated to MINUSTAH were not required to be repurposed for cholera reparations, many member states took back their contributions, and by July 2017 just $9.22 million had been raised. From the beginning, MINUSTAH has been squeezed between traditional conservative sectors—which demanded more action—and the leftist parties, mainly linked to ousted President Aristide , which criticize its actions and constantly appeal for its departure. [ citation needed ] Even though mostly composed by military forces—the recruitment of large numbers of foreign police officers has proven difficult—the United Nations Stabilization Mission in Haiti is a police mission of the United Nations dispatched to a country facing uncontained violence stemming from political unrest and from common criminals. Partidaries of former President Jean-Bertrand Aristide have characterized MINUSTAH as an attempt by the United States, Canada and France to neutralize the supporters of Fanmi Lavalas , Aristide 's party. and secure the more pro-Western government of Gérard Latortue . The mission was mandated to assist and reinforce the action of the Haitian Police in Port-au-Prince's slums. On 6 July 2005, MINUSTAH, led by Brazilian general Augusto Heleno carried out a raid in the Cité Soleil section of Port-au-Prince . The raid targeted a base of illegally armed rebels led by the known bandit Dread Wilme . Reports from pro-Lavalas sources, as well as journalist Kevin Pina , contend that the raid targeted civilians and was an attempt to destroy the popular support for Haiti's exiled former leader, Aristide, before scheduled upcoming elections. Estimates on the number of fatalities range from five to as high as 80, with the higher numbers being claimed by those reporting that the raid targeted civilians. All sources agree that no MINUSTAH personnel were killed. All sources also agree that Dread Wilme (born "Emmanuel Wilmer") was killed in the raid. MINUSTAH spokespeople called Wilme a "gangster." Other sources, such as the pro-Aristide Haitian Lawyers Leadership Network call Wilme a community leader and a martyr . The incident has been since heralded by groups who oppose the MINUSTAH presence in Haiti and who support the return of ousted President Aristide. MINUSTAH has also been accused by Fanmi Lavalas supporters of allowing the Haitian National Police to commit atrocities and massacres against Lavalas supporters and Haitian citizens. On 6 January 2006, UN mission head Juan Gabriel Valdés announced that MINUSTAH forces would undertake another action on Cité Soleil. On one side, traditional Haitian sectors criticized MINUSTAH for "standing by and not stopping the violence taking place in slums like Cité Soelil"; on the other hand, human rights groups were prepared to condemn MINUSTAH for any collateral damage deriving from their actions. It was reported that Valdés said, "We are going to intervene in the coming days. I think there'll be collateral damage but we have to impose our force, there is no other way." MINUSTAH soldiers have been accused of being involved in a number of sexual assault cases. In 2011, four Uruguayan UN marines were accused of gang raping a 19-year-old Haitian male in Port-Salut . It was said the alleged rape was recorded with a cell phone by the peacekeepers themselves and leaked to the Internet. The teenager and his family were forced to relocate their house after the video went viral. In March 2012, three Pakistani MINUSTAH officers were found guilty of raping a mentally challenged 14-year-old boy in the town of Gonaïves . Pakistani officials sentenced each officer to one year in a Pakistan prison. In November 2007, 114 members of the 950-member Sri Lanka peacekeeping contingent in Haiti were accused of sexual misconduct and abuse. 108 members, including 3 officers were sent back after being implicated in alleged misconduct and sexual abuse. UN spokeswoman Michele Montas said: "The United Nations and the Sri Lankan government deeply regret any sexual exploitation and abuse that has occurred." The Sri Lankan Officials claim that there is little tangible evidence on this case. After inquiry into the case the UN Office of Internal Oversight Services (OIOS) has concluded 'acts of sexual exploitation and abuse (against children) were frequent and occurred usually at night, and at virtually every location where the contingent personnel were deployed.' The OIOS is assisting in the pending legal proceedings initiated by the Sri Lankan Government and has said charges should include statutory rape "because it involves children under 18 years of age". In 2015, a new investigation was released, accusing MINUSTAH peacekeepers of abusing further hundreds of Haitians. In 2010, Gérard Jean-Gilles, a 16-year-old Haitian boy who ran miscellaneous errands for the Nepalese soldiers in Cap-Haitien , was found dead hanging inside of MINUSTAH's Formed Police Unit base. UN personnel denied responsibility, claiming that the teen committed suicide. The troops released the body for autopsy seventy-two hours after the death; the examination ruled out suicide as a potential cause of death. Nepalese UN troops were also accused for other misdeeds. Several days before the Jean-Gilles incident, the local press charged a Nepalese soldier of torturing a minor in a public area in Cap-Haitien. The soldier was said to have forced "his hands into the youth's mouth in an attempt to separate his lower jaw from his upper jaw, tearing the skin of his mouth." People related to Fanmi Lavalas (Haiti's largest leftist party) have repeatedly expressed discontent with MINUSTAH and its management of political public dissent. Protests on 15 November 2010 in Cap-Haitien and other areas of the country resulted in at least two civilian deaths and numerous injuries. MINUSTAH stated that the protests seemed politically motivated, "aimed at creating a climate of insecurity on the eve of elections." Regarding the deaths, it stated that a UN peacekeeper shot out of self-defence. Fanmi Lavalas (the party of former President Aristide) took part in the burial of Catholic priest Gerard Jean-Juste on 18 June 2009. It was later reported that the procession was suddenly interrupted by gunfire. Fanmi Lavalas witnesses said that MINUSTAH Brazilian soldiers opened fire after attempting to arrest one of the mourners; the UN denied the shooting and reported that the victim had been killed by either a rock thrown by the crowd or a blunt instrument. A trial is currently in progress at the Inter-American Court of Human Rights (IACHR). The case, brought forward by Mario Joseph from the Bureau des Avocats Internationaux (BAI) and Brian Concannon from the Institute for Justice & Democracy in Haiti , concerns Jimmy Charles, a grassroots activist who was arrested by UN troops in 2005, and handed over to the Haitian police. His body was found a few days later in the morgue, filled with bullet holes. The BAI filed a complaint in Haitian courts, to no avail, and in early 2006 it filed a petition with the IACHR. The IACHR accepted the case regarding the State of Haiti, and rejected the complaint against Brazil. On 13 April 2017, the Security Council announced the replacement of this mission by a follow-up operation called the United Nations Mission for Justice Support in Haiti (MINUJUSTH) from 15 October 2017. Even though mostly composed by military forces—the recruitment of large numbers of foreign police officers has proven difficult—the United Nations Stabilization Mission in Haiti is a police mission of the United Nations dispatched to a country facing uncontained violence stemming from political unrest and from common criminals. Partidaries of former President Jean-Bertrand Aristide have characterized MINUSTAH as an attempt by the United States, Canada and France to neutralize the supporters of Fanmi Lavalas , Aristide 's party. and secure the more pro-Western government of Gérard Latortue . The mission was mandated to assist and reinforce the action of the Haitian Police in Port-au-Prince's slums. On 6 July 2005, MINUSTAH, led by Brazilian general Augusto Heleno carried out a raid in the Cité Soleil section of Port-au-Prince . The raid targeted a base of illegally armed rebels led by the known bandit Dread Wilme . Reports from pro-Lavalas sources, as well as journalist Kevin Pina , contend that the raid targeted civilians and was an attempt to destroy the popular support for Haiti's exiled former leader, Aristide, before scheduled upcoming elections. Estimates on the number of fatalities range from five to as high as 80, with the higher numbers being claimed by those reporting that the raid targeted civilians. All sources agree that no MINUSTAH personnel were killed. All sources also agree that Dread Wilme (born "Emmanuel Wilmer") was killed in the raid. MINUSTAH spokespeople called Wilme a "gangster." Other sources, such as the pro-Aristide Haitian Lawyers Leadership Network call Wilme a community leader and a martyr . The incident has been since heralded by groups who oppose the MINUSTAH presence in Haiti and who support the return of ousted President Aristide. MINUSTAH has also been accused by Fanmi Lavalas supporters of allowing the Haitian National Police to commit atrocities and massacres against Lavalas supporters and Haitian citizens. On 6 January 2006, UN mission head Juan Gabriel Valdés announced that MINUSTAH forces would undertake another action on Cité Soleil. On one side, traditional Haitian sectors criticized MINUSTAH for "standing by and not stopping the violence taking place in slums like Cité Soelil"; on the other hand, human rights groups were prepared to condemn MINUSTAH for any collateral damage deriving from their actions. It was reported that Valdés said, "We are going to intervene in the coming days. I think there'll be collateral damage but we have to impose our force, there is no other way." MINUSTAH soldiers have been accused of being involved in a number of sexual assault cases. In 2011, four Uruguayan UN marines were accused of gang raping a 19-year-old Haitian male in Port-Salut . It was said the alleged rape was recorded with a cell phone by the peacekeepers themselves and leaked to the Internet. The teenager and his family were forced to relocate their house after the video went viral. In March 2012, three Pakistani MINUSTAH officers were found guilty of raping a mentally challenged 14-year-old boy in the town of Gonaïves . Pakistani officials sentenced each officer to one year in a Pakistan prison. In November 2007, 114 members of the 950-member Sri Lanka peacekeeping contingent in Haiti were accused of sexual misconduct and abuse. 108 members, including 3 officers were sent back after being implicated in alleged misconduct and sexual abuse. UN spokeswoman Michele Montas said: "The United Nations and the Sri Lankan government deeply regret any sexual exploitation and abuse that has occurred." The Sri Lankan Officials claim that there is little tangible evidence on this case. After inquiry into the case the UN Office of Internal Oversight Services (OIOS) has concluded 'acts of sexual exploitation and abuse (against children) were frequent and occurred usually at night, and at virtually every location where the contingent personnel were deployed.' The OIOS is assisting in the pending legal proceedings initiated by the Sri Lankan Government and has said charges should include statutory rape "because it involves children under 18 years of age". In 2015, a new investigation was released, accusing MINUSTAH peacekeepers of abusing further hundreds of Haitians. In 2010, Gérard Jean-Gilles, a 16-year-old Haitian boy who ran miscellaneous errands for the Nepalese soldiers in Cap-Haitien , was found dead hanging inside of MINUSTAH's Formed Police Unit base. UN personnel denied responsibility, claiming that the teen committed suicide. The troops released the body for autopsy seventy-two hours after the death; the examination ruled out suicide as a potential cause of death. Nepalese UN troops were also accused for other misdeeds. Several days before the Jean-Gilles incident, the local press charged a Nepalese soldier of torturing a minor in a public area in Cap-Haitien. The soldier was said to have forced "his hands into the youth's mouth in an attempt to separate his lower jaw from his upper jaw, tearing the skin of his mouth." People related to Fanmi Lavalas (Haiti's largest leftist party) have repeatedly expressed discontent with MINUSTAH and its management of political public dissent. Protests on 15 November 2010 in Cap-Haitien and other areas of the country resulted in at least two civilian deaths and numerous injuries. MINUSTAH stated that the protests seemed politically motivated, "aimed at creating a climate of insecurity on the eve of elections." Regarding the deaths, it stated that a UN peacekeeper shot out of self-defence. Fanmi Lavalas (the party of former President Aristide) took part in the burial of Catholic priest Gerard Jean-Juste on 18 June 2009. It was later reported that the procession was suddenly interrupted by gunfire. Fanmi Lavalas witnesses said that MINUSTAH Brazilian soldiers opened fire after attempting to arrest one of the mourners; the UN denied the shooting and reported that the victim had been killed by either a rock thrown by the crowd or a blunt instrument. A trial is currently in progress at the Inter-American Court of Human Rights (IACHR). The case, brought forward by Mario Joseph from the Bureau des Avocats Internationaux (BAI) and Brian Concannon from the Institute for Justice & Democracy in Haiti , concerns Jimmy Charles, a grassroots activist who was arrested by UN troops in 2005, and handed over to the Haitian police. His body was found a few days later in the morgue, filled with bullet holes. The BAI filed a complaint in Haitian courts, to no avail, and in early 2006 it filed a petition with the IACHR. The IACHR accepted the case regarding the State of Haiti, and rejected the complaint against Brazil. On 13 April 2017, the Security Council announced the replacement of this mission by a follow-up operation called the United Nations Mission for Justice Support in Haiti (MINUJUSTH) from 15 October 2017. Eighteen Rwanda National Police officers were decorated with service medals for their outstanding peacekeeping role in Haiti.

Wiki