Talk:Human mortality from H5N1

message: With just over 300 cumulative cases and less than 200 cumulative deaths WORLDWIDE!! What are you people SMOKING?? - unsigned
:H5N1 has evolved into a flu virus strain that infects more species than any previously known flu virus strain, is deadlier than any previously known flu virus strain, and continues to evolve becoming both more widespread and more deadly causing a leading expert on avian flu to publish an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives. Since the article was written, the world community has spent billions of dollars fighting this threat with limited success. WAS 4.250 16:00, 30 July 2007 (UTC)
thread_title:  H5N1 flu is a concern due to the global spread of H5N1 that constitutes a pandemic threat 

message: I maintain Template:H5N1 case graph (used in Global spread of H5N1) and Template:H5N1 Human Mortality (used in Transmission and infection of H5N1). I may be away from computer access for a week or two from time to time, and would hate for these not to be up to date, in case there are WHO updates during those times. Would anybody be willing to pinch hit in case I'm unable to get to a computer to update them? I've written some detailed instructions on what to do here. If you've ever used OpenOffice calc and GIMP, you're already qualified. If not, and you'd like to learn a couple of awesome tools, the directions are plenty complete enough to learn what you need to know. Once you've learned how to do it, it only takes about 15 minutes to do an update, so it's not a major time commitment. Any takers? Waitak 09:02, 29 May 2006 (UTC)
thread_title:  Waitak's Instructions - 'Maintaining graphs' 

message: Please help prepare this stub for inclusion in the main article.
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As the U.N. has observed,
"One especially important question that was discussed is whether the H5N1 virus is likely to retain its present high lethality should it acquire an ability to spread easily from person to person, and thus start a pandemic. Should the virus improve its transmissibility by acquiring, through a reassortment event, internal human genes, then the lethality of the virus would most likely be reduced. However, should the virus improve its transmissibility through adaptation as a wholly avian virus, then the present high lethality could be maintained during a pandemic."
from the journal http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_3C.pdf|
title: Influenza research at the human and animal interface 
author: WHO working group on influenza research at the human and animal interface
date: November 2, 2006
pages=15
http://www.who.int/entity/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_3/en/index.html
As pointed out in http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030040 | Subbarao K, Luke C (2007) H5N1 Viruses and Vaccines. PLoS Pathog 3(3): e40 doi:10.1371/journal.ppat.0030040H5N1
"In order to cause a pandemic, H5N1 viruses will have to acquire the ability to transmit efficiently from person to person. The H5 hemagglutinin (HA) is found in influenza viruses that typically infect avian species, so efficient person-to-person spread could happen if the H5N1 virus reassorts, or exchanges genes, with circulating human influenza viruses giving rise to a virus with the H5 HA (to which the population is not immune) in a gene constellation that confers the property of transmissibility. Alternatively, efficient person-to-person spread could occur if the H5N1 virus evolves and adapts to more efficient replication and transmissibility in the human population.
Two observations have led to questions about the likelihood of a reassortant H5N1 virus causing a pandemic. First, reassortant viruses have not been isolated despite ongoing H5N1 outbreaks in birds and infections in humans, even with concurrent circulation of human influenza viruses since 2003. Second, laboratory studies have found that reassortant viruses that derived the surface glycoprotein genes from an H5N1 virus and internal protein genes from an H3N2 influenza A virus were not efficiently transmitted and were somewhat less infectious to ferrets (an animal model for human influenza) than the wild-type H5N1 viruses [2]. The concern that an H5N1 virus could adapt to the human host and acquire mutations that confer transmissibility prompts very careful analysis of each cluster of human H5N1 infections that is reported ( [1,3–5]). At present, the data suggest that human-to-human transmission is inefficient and very limited. Nevertheless, from the standpoint of public health preparedness, it is important to move forward in developing approaches for dealing with H5N1 in humans."
(end of Subbarao quote)
There are a number of sub-strains, or clades, of H5N1 in circulation. Milder clades, such as the "V" clade, may already be circulating in mammals such as cats, dogs, and pigs without attracting much attention. If so, early establishment in mammals would seem to favor emergence of the first wave of an H5N1 pandemic from the "V" clade, rather than the "Z" clade. A pandemic that emerges from the "V" clade seems likely to be relatively mild, since many human infections from this clade have been very mild or asymptomatic. The "Z" clade is the most lethal in humans, and attracts the most attention. The "Z" clade's bid for pandemic emergence is favored by its widespread dispersal in birds. Compared to a "V" clade pandemic, a pandemic evolving from the "Z" clade is likely to be quite lethal.
As shown below, the mechanisms by which a "Z" pandemic would have to evolve may be the slower processes of recombination or mutation, rather than the quicker reassortment. If so, it might be delayed in emerging long enough for vaccines or other protective measures to be put in place.
As shown below, the likelihood of an initially very lethal avian variant emerging without reassortment appears high. However a corollary is that emergence of such a variant is likely to occur more slowly than might a reassortant, and if it does, it will allow more time to prepare and distribute vaccines that may provide a herd immunity which blunts or avoiding the worst effects of a pandemic whose scale might otherwise be unprecedented.  
Another possibility is that more pathogenic viruses have an advantage in infecting birds, and hence are selected for in avian hosts.  Less pathogenic varieties would have an advantage in mammalian hosts -- allowing the sick mammal to infect others before dying.  A mild mammalian line could become established in mammals, while a mild variant remained predominant in birds.  The mammalian line would be likely to reach humans first, and confer some immunity while causing some disease and death, but much less than if a pathogenic strain had jumped directly to humans from birds.  In a third step, the mammalian-adapted low-pathogenic strain and the avian-adapted high pathogenic strain could swap genes, and among the resulting reassortants or recombinants could be a quite lethal hybrid quite contagious to humans.  Hopefully human immunity from the pre-circulated mammalian strain would soften the below, and any low-pathogenic hybrid that emerged would have a competitive advantage in humans over the high-pathogenic strains, blunting their spread.  
Milder pandemics are most likely to emerge when a human, pig, cat, or other animal is infected with both an H5N1 influenza and a human-adapted influenza, allowing the two flus to exchange gene packets as they reproduce within the host's cells. The resultant mild reshuffled virus might have the genes from the human virus that make it readily contagious, principally upper respiratory symptoms that allow it to be spread by coughing, hand contact, or fomites. Yet from the H5N1 ancestor, it might inherit genes for its H5 and N1 surface receptors that most human immune system cannot yet recognize or combat. If the resulting virus is at least mildly debilitating, its spread would be a pandemic, because the other two necessary elements would be present; efficiently-transmission from the human flu, and surface antigens as yet unrecognized by human immune systems. As more people and other mammals become infected with H5N1, the risks of such a reassortment increase.
The question of whether the reassorted influenza would be as deadly as current avian H5N1 infections in humans, as mild as a seasonal influenza, or something in between in general is a wild card. Genes that make H5N1 influenza deadly are not necessary for it to be a pandemic. Efficient transmission and unrecognized surface antigens are enough. Whether the H5N1 genes coding for lethality in humans are included in a reassortment or not is almost a matter of indifference to the emergence of the original pandemic strain. If it is efficient in transmission and there is no herd immunity in its host population, it can spread even if it is rather lethal among the hosts, so long as each lives long enough to infect two others. Lethality to humans is, however a matter of considerable interest to humans as we try to assess our risks.
H5N1 avian influenza includes a novel HA molecule, denominated H5, which is one of the novel surface molecules to which the human population as yet has no immunity. The H5 surface antigen is the most likely site for the genes that make H5N1 avian influenza lethal in humans (and pathogenic in birds). "... [T]he high pathogenicity of the H5N1 viruses in poultry, mice, and ferrets 'depends primarily on the polybasic cleavage site in the HA molecule ...'". Lethality to ferrets is considered a proxy for lethality to humans, as the immune responses are similar. Thus both the lethality of H5N1 and its novelty (which make it effectively invisible to current human immune defenses) are tightly bound in the same H5 gene. The saving grace for the human race has been that the structure of the HA gene is also essential to the virus's invasion of a host, and up until now this H5 gene has remained very poorly adapted to infecting human hosts. Extant H5 variants remain instead well adapted to bind with and infect bird hosts. It is cause for concern, however, that two mutations or recombinations have been observed in variants isolated from human victims that appear designed to increase its ability to bind to and infect humans. In Indonesia, almost all H5N1 found in human cases have shown these changes, while almost no bird cases from Indonesia have them. A report in science has convincingly shown that only two changes are needed to change from the highly-contagious 1918 human pandemic virus to a non-contagious avian virus. http://www.sciencemag.org/cgi/content/short/315/5812/655 http://scienceblogs.com/effectmeasure/2007/02/transmissibility_in_the_1918_f_1.php http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/feb0207virus.html It is significant that both changes are on the HA gene.
As long as the traits of lethality, invisibility to the human immune system, and poor adaptation to infecting humans remain combined on the same H5 gene, a human pandemic probably cannot evolve through the quick and simple process of reassortment of gene packets within a "mixing vessel" host that has caught both an avian and a human flu at the same time. If it could, a pandemic likely would already have broken out, though perhaps not a very lethal one -- the milder pandemics late in the 20th century appear to have been reassortants. If lethality, novelty, and contagiousness are on the same H5 gene, it is more likely that H5N1 will instead be able to easily infect humans only when it has evolved that ability through the hit-and-miss (and usually slower) processes of mutation or recombination. These are processes by which the molecules within a single gene may be are changed. The resulting slowness may help explain why, as some (Robert Webster?) have wondered, a pandemic has not already broken out. The slowness of a pandemic to appear is very good news, because it has allowed scientists to prepare defenses. The longer breakout of a full-scale pandemic is delayed, the better the medical defenses that are likely to be in place. By late 2008 or 2009, it is likely that one or more reasonably safe and effective pre-pandemic vaccines may be ready to stockpile or to administer to the population that there will be herd immunity in place before a pandemic emerges. In a few more years, more resources designed to increase capacity for rapid development and distribution of specific pandemic vaccinations will be in place. Stocks of existing antivirals will be higher. And quicker testing and additional effective drugs or other treatments may also be ready to deploy.
The bad news is that if H5N1 adapts into a human pandemic through recombination or mutation (rather than reassortment) is more likely to be very lethal when it comes. Recent historical experience reinforces this conclusion. Examination of the reconstructed lethal Spanish Flu virus shows it was a predominantly avian virus that had made only the relatively few molecular changes necessary to infect humans, analogous to the changes that the H5N1 virus now appears to be undergoing. The far milder later pandemics in the 20th century were reassortants.
A July 2006 study reported in PNAS suggests that the viruses resulting when avian H5N1 influenza is reassorted with human influenza viruses, the deadliness of the H5N1 virus may be retained by the reassorted "daughter" virus, but those daughter viruses may lack contagiousness beyond the limited contagiousness in mammals of the parent H5N1. The study, is titled _"Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model"_. http://www.pnas.org/cgi/content/abstract/0605134103v1 ("Ferret reassortant study") Its results are those to be expected if the deadliness, novelty, and lack of mammalian adaptation are all combined on the same gene, so that reassorting that intact gene with other genes fails to separate those three characteristics.
In the ferret reassortant study, hybrid influenza viruses were created in biosecure laboratories by reassorting the genes from avian H5N1 influenza from Indonesia with those from an H3N2 (human adapted) flu virus. The resulting hybrid was tested on ferrets. The immune system of ferrets is the best known analogue of the human immune system known for testing influenza viruses and treatments. Obviously, H5N1 cannot be tested directly on living humans.
It would have been reassuring if the reassortant influenza viruses resulting from the ferret reassortant study had no longer been as lethal as the original H5N1, perhaps dropping the deadly H5N1 genes that often cause a deadly "cytokine storms" in humans, and picking up more benign human genes in their place. Unfortunately, all seven ferrets infected with the hybrid virus died. In this ferret H5N1 reassortment study, it thus appears that the cytokine storm or other genes causing death were retained by the reassortant viruses, which remained 100% deadly in ferrets, no less lethal than the Indon05 virus from which they were reassorted. Emergence of a 100% deadly virus that causes high URI (Upper Respiratory Infection) titers may be the buried headline of the PNAS study. The ferret reassortant virus represents perhaps a half-step toward a pandemic virus, because high URI titers of virus may be another step along a path leading to transmissibility among humans. But since lethality was retained, it is a half-step toward an exceptionally deadly pandemic virus.
The failure of a less-lethal virus to emerge in reassortment and the fact that high URI titers were observed are both threatening outcomes. Against this background, the fact that the ferrets in the next cage in the were not infected is of limited comfort. It suggests time to transmissibility may be higher than with reassortment, but the result may be deadlier.
Although influenza viruses may be nearly indifferent to lethality as they emerge, evolutionary pressures immediately begin to favor the less lethal variants among the efficiently transmissible novel strains. A very lethal pandemic strain that kills its hosts before they cam infect two other potential hosts will be outcompeted by one that lets its hosts live longer. As the lethal wave of the Spanish Flu of 1918 progressed, it was observed that communities, and even individuals within communities, who were infected later did not experience outcomes as lethal as experienced by those who were infected earlier.
The Spanish Flu itself may provide a model for the inclusion or exclusion of a lethality gene in an initial pandemic in another way. There is reason to believe that the Spanish Flu existed for some time before any human outbreak was observed.[1] One theory is that the virus strain originated an Kansas, either at Fort Riley or in Haskell County. An alternate (but not inconsistent) account holds that dozens of soldiers who fell sick with the signs of a killer flu after the Battle of the Somme in the winter of 1916-1917, and two months later at the large Aldershot base in England died of an early and exceptionally lethal (40% mortality) version of what was to later be known as the "Spanish Flu." [2]
One viral variant circulating in late 1917 or early 1918, was so mild as to be called the "three day flu." [3] An article in an Italian medical journal questioned whether this strain was a flu at all. Evidence that a lethal flu was beginning to circulate appears in evidence of an early wave of the 1918 influenza pandemic in New York City. Unfortunately, the Spanish flu in 1918 apparently picked up a genes coding for contagiousness and lethality via a cytokine storm, and in mid-1918 began a deadly wave (2% mortality) that did, however, begin to evolve toward a less-lethal form. It appears that the three-day flu was indeed a variant of the same virus, as those who had been exposed to the notably mild "three-day" flu in the Spring of 1918 had at least some immunity to the lethal later wave when it emerged.
"In 1918, the pandemic began with a fairly mild wave in the spring, followed by a far more severe wave in the fall. People who were exposed to the disease in the spring were much less likely to get sick in the fall, he said." (comment by John M. Barry, author of The Great Influenza, "2007 SUMMIT COVERAGE: Notable quotes from business summit on pandemic issues," Feb 8, 2007 (CIDRAP News)). http://www.cidrap.umn.edu/cidrap/content/influenza/biz-plan/news/feb0807quotes.html
Similar waves were observed in New South Wales, Australia. http://www.health.nsw.gov.au/public-health/phb/HTML2006/julaug06html/article3p103.html#figure1 AN AUSTRALIAN PERSPECTIVE OF THE 1918–1919 INFLUENZA PANDEMIC The NSW Public Health Bulletin Citation: N S W Public Health Bull 2006; 17 (7–8) 103–107 Peter Curson and Kevin McCracken
If, by contrast, a H5N1 pandemic emerges that is deadly from the very beginning, it will not be running against the headwinds of this kind of pre-existing herd immunity, and contagiousness may be worse. In this context, the failure of the ferret study recombinants to exhibit reduced lethality is especially disappointing. - unsigned by 67.101.66.127 at 09:19, 3 August 2006
    CROSSTALK:  This study's conclusion is "These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait." Our concluding more than that would be original research. We do have an article on Flu research where a short summary of this highly inconclusive experiment could be mentioned; but this article is not the place for such speculation. By the way, I do not believe that when spanish flu first emerged that it was mild. You might wish to review the government coverup of the spanish flu for possible sources of reports of "oh its not so bad". WAS 4.250 17:46, 3 August 2006 (UTC)
thread_title: Predicting evolving pandemic lethality - genes

message: User:67.101.68.164, regarding your edit "The H5 surface antigen is also the most likely site for the lethality of H5N1 in humans (and pathogenicity in birds)." above; you may wish to read H5N1 genetic structure which shows otherwise. The amino acid substitution (Ser31Asn) in the M2 gene in some H5N1 genotypes is associated with amantadine resistance which increases lethality. However the pathogenicity of H5N1/97 was related to the nonstructural (NS) gene. NS codes for two nonstructural proteins (NS1 and NEP). The NS1 gene of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia is believed to be responsible for an enhanced proinflammatory cytokine response (especially TNFa) induced by these viruses in human macrophages. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, the researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus. So we now now why H5N1 is so deadly. Right? Wrong. Polymerase encoding gene segments are also implicated. PA codes for the PA protein which is a critical component of the viral polymerase. PB1 codes for the PB1 protein and the PB1-F2 protein. The PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza and 75% of H5N1 human virus isolates from Vietnam had a mutation consisting of Lysine at residue 627 in the PB2 protein; which is believed to cause high levels of virulence. Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a lysine. OK, so now we know that the cause is the gene mutations just mentioned, right? Wrong. It's more complicated than that. The H5N1 genes work together in ways we don't yet understand. Research is continuing. WAS 4.250 01:24, 4 December 2006 (UTC)
thread_title: User talk:67.101.68.164 -- genes involved in lethality

message: The main article states that the apparent rise in global lethality in 2006 "has been interpreted by some to mean that the virus itself is becoming more deadly over time."
In fact, the apparent rise in global lethality from 2005 to 2006 may be mostly or completely explained by the rise in 2005, then extinguishment later that year of a very mild strain in North Vietnam with a mortality rate of only about 10%. The large number of cases of this strain, while it lasted, brought down the worldwide mortality averages, which outside of Vietnam continued at about two deaths for every three cases. The continuation of the 66% lethal average once the Northern Vietnamese strain was extinguished thus appear to be an accelleration of lethality among existing strains, but more accurately reflects Vietnam's success in stamping out the (unfortunately) least lethal strain.
In 2005, 61 cases were from Vietnam, of only 95 cases worldwide. (in 2005)
The above could be followed by a new paragraph, begining with and continuing the existing text,
"The global mortality rate is, nonetheless, a crude summary of a complex situation with many contributing factors."[1][2]
—The preceding unsigned comment was added by 67.101.67.244 (talk • contribs • WHOIS) .
    You've become a significant contributor to these pages. How about signing up? Waitak 01:51, 21 August 2006 (UTC)
thread_title: Vietnam contributed to low worldwide death rate in 2005

message: Since Indonesia stopped sending samples to the WHO in February, 2007, and the WHO stopped including Indonesian cases in its case and fatality reports, the majority of cases have been from Egypt, where a much milder form of bird flu seems to be circulating, infecting many but killing only a minority. The result is a slowing of the number of cases, and a plummeting of the number of deaths reported to and confirmed by the WHO. Since the drumbeat of cases and deaths goes on in Indonesia, the world is not safer, though the WHO reports make it seem so.
Perhaps if the Egyptian strain breaks into human-to-human contagion before the Indonesian strain, the initial wave of the pandemic will be milder, and some residual herd immunity may be created that slows any later wave of the Indonesian strain. —The preceding unsigned comment was added by 67.101.68.104 (talk) 00:51, 7 April 2007 (UTC)
thread_title: Continued Lethality?

message: Seasonal Flumist is a group of three highly attenuated live viruses.  Those vaccinated have a tendency to inoculate others around them inadvertently.  
Pre-pandemic herd immunity could be safely achieved by connecting some of the surface antigens from H5N1 to Flumist, but without H5N1's lethality (or morbidity) genes.  If this creates herd immunity, there will be, by definition, no pandemic.  
Because Flumist involves live viruses (albeit highly attenuated), immunity acquired by current seasonal Flumist inoculation is much broader and longer-lasting than immunity from shots.  Even without H5 or N1 surface antigens, the broad immunity conferred by Flumist inoculation (mucosal and cellular, as well as humoral immunity) may confer some unknown degree of immunity to all other flus, including H5N1. 
A study suggested that the N1 in the seasonal H1N1 influenza A shots (or something else in those shots) confers at least some immune protection against H5N1.  
 
The H5 or N1 antigens from H5N1 could be added to the current seasonal Flumist, and if they were, herd immunity would begin to be acquired in the process of routine seasonal vaccination itself, and thus at very low social cost and far in advance of an actual pandemic.  An advantage of this approach is that over time, robust herd immunity could be built up, in the sense that not only the current H5N1 would run into immunity in the herd, but also the H5 and N1 surface antigens that had been included in earlier annual Flumist inoculations. - User talk:Ocdcntx
"MedImmune, Inc. (Nasdaq: MEDI) announced today that the National Institutes of Health (NIH) has begun enrolling participants in a Phase 1 study of an intranasal H5N1 influenza vaccine candidate based on the company's live, attenuated vaccine technology. Investigators at MedImmune and Johns Hopkins Bloomberg School of Public Health Center for Immunization Research, where the study will be conducted, are hopeful that a live, attenuated intranasal influenza vaccine would be as effective against potential pandemic A strains as it has been shown to be against seasonal A strains of influenza."Source I'll definitely have to add this data to Flu research and H5N1 clinical trials and FluMist. WAS 4.250 16:44, 3 August 2007 (UTC)
thread_title: Add H5 or N1 antigens to seasonal vaccinations for herd immunity

message: On August 22, 2007, an Indonesian woman, 28, chicken trader died of H5N1 bird flu after 4 days of hospitalization. She was the 2nd person to die of bird flu on Bali, raising the death toll in the nation due to the disease to 84. Tests in 2 local laboratories were positive for the H5N1 strain of the disease. 194 people — the majority of them in Indonesia have died since 2003, according to the World Health Organization. ITH, Bird flu kills Balinese woman, raises death toll to 84  —Preceding unsigned comment added by 67.101.68.220 (talk) 19:22, 7 October 2007 (UTC)
thread_title: Interesting newsy details of one case (snipped from general overview area of main article, where it was misplaced)

message: Unfortunately, the excellent graphic Waitak provided is not maintain (since April 2007).  It is increasingly out of date, and none but Waitak know how to maintain it.   
The WHO has a graphic showing cumulative fatality rates at 
http://www.wpro.who.int/NR/rdonlyres/7549914F-5C83-4418-8C20-007ADCC07C61/0/s3.jpg
Maybe it should be added or substituted?  —Preceding unsigned comment added by 69.3.75.111 (talk) 22:50, 6 March 2008 (UTC)
thread_title:  WHO's more current Graphic for cumulative fatality

message: http://jech.bmj.com/cgi/content/abstract/62/6/555  —Preceding unsigned comment added by 64.105.0.30 (talk) 23:07, 5 June 2008 (UTC)
replies: text: Thanks. I'll add it to the article. WAS 4.250 (talk) 23:23, 5 June 2008 (UTC)
thread_title:  BMJ estimates likely fatality 

message: Lethality patterns suggest the summer wave of the Spanish Influenza may have protected against the lethal fall wave.
"The summer wave may have provided partial protection against the lethal fall wave."
Viggo Andreasen, Cécile Viboud, and Lone Simonsen
Epidemiologic Characterization of the 1918 Influenza Pandemic Summer Wave in Copenhagen: Implications for Pandemic Control Strategies 
MAJOR ARTICLE
The Journal of Infectious Diseases 2008;197:270–278
© 2007 by the Infectious Diseases Society of America. All rights reserved.
http://www.journals.uchicago.edu/doi/abs/10.1086/524065 
0022-1899/2008/19702-0015$15.00
DOI: 10.1086/524065
If we are fortunate enough that a first wave of H5N1 sweeps the earth first, we must be aware that a high-fatality wave is likely to follow it.  
Exposure to the first wave may be protective against the later waves -- a kind of natural vaccination.  
The above meta-analysis (and other studies of the various waves of the Spanish Influenza) suggest that those who came down with the first, relatively innocuous wave of the Spanish Influenza had at least some protection when it was quickly followed by a similar, but lethal wave.  —Preceding unsigned comment added by 69.3.11.30 (talk) 19:33, 20 October 2008 (UTC)
thread_title:  Lethality patterns suggest the summer wave of the Spanish Influenza may have protected against the lethal fall wave -- may be same with H5N1 

message: Pre-pandemic vaccination is already underway in Japan and studied in Switzerland.  
An opinion piece in the Lancet has called for pre-pandemic vaccination generally: 
:"WHO and governments should give urgent consideration to the use of these vaccines for the priming of individuals or communities who would be at greatest risk of infection if an H5N1 influenza pandemic were to emerge."
Personal View
Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans
http://www.thelancet.com/journals/laninf/article/PIIS1473309908702329/abstract 
The Lancet Infectious Diseases 2008; 8:650-658
DOI:10.1016/S1473-3099(08)70232-9
Dr Lance C Jennings PhD email address a Corresponding Author Information,   Prof Arnold S Monto MD b,   Prof Paul KS Chan MD c,   Prof Thomas D Szucs MD d   and   Prof Karl G Nicholson MD e
Summary
The history of pandemic influenza, along with the evolving epizootic of the highly pathogenic avian influenza A (H5N1) virus and the severity of associated human infections, serve as a warning to the world of the threat of another influenza pandemic. Conservative estimates suggest that up to 350 million people could die and many more would be affected, causing disruption to health-care systems, society, and the world's economy. WHO has encouraged countries to prepare in advance by developing influenza pandemic preparedness plans that involve public-health and pharmaceutical interventions. Vaccination is a cornerstone of these plans; however, a pandemic vaccine cannot be manufactured in advance because the next pandemic virus cannot be predicted. The concepts of vaccine stockpiling and prepandemic vaccination have thus become attractive. Human H5N1 vaccines are currently available and can induce heterotypic immunity. WHO and governments should give urgent consideration to the use of these vaccines for the priming of individuals or communities who would be at greatest risk of infection if an H5N1 influenza pandemic were to emerge.
Affiliations
a. Microbiology Department, Canterbury Health Laboratories, and Department of Pathology, University of Otago, Christchurch, New Zealand
b. University of Michigan School of Public Health, Ann Arbor, MI, USA
c. Department of Microbiology and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China
d. Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland
e. Department of Infectious Disease and Tropical Medicine, Leicester Royal Infirmary, Leicester, UK
Corresponding Author InformationCorrespondence to: Dr Lance C Jennings, Canterbury Health Laboratories, PO Box 151, Christchurch, New Zealand  —Preceding unsigned comment added by 68.165.11.156 (talk) 15:35, 27 October 2008 (UTC)
thread_title:  Widespread lethality can be reduced by pre-pandemic vaccination  

message: Japan has inoculated 6,000 health care workers with a pre-pandemic vaccine, and is planning how to proceed with widespread vaccinations, particularly workers who would provide utilities during an outbreak.Pre-pandemic bird flu shots eyed / Health ministry to urge study of potential early vaccination recipients 
|
(Daily Yomiuri Online + AP -- Apr. 25, 2009)
http://www.yomiuri.co.jp/dy/national/20090425TDY03103.htm  —Preceding unsigned comment added by 69.3.11.131 (talk) 18:46, 25 April 2009 (UTC)
thread_title:  Japan studying pre-pandemic vaccinations 

message: ":... 
:Lone Simonsen, an epidemiologist at George Washington University, said she expected a third wave in December or January, possibly beginning in the South again.
:“If people think it’s going away, they can think again,” Dr. Simonsen said.
:Based on death rates in New York City and in Scandinavia, she has argued that both 1918 and 1957 had mild summer waves followed by two stronger waves, one in fall and one in midwinter."
"Signs That Swine Flu Has Peaked"
By DONALD G. McNEIL Jr.
Published: November 20, 2009 
http://www.nytimes.com/2009/11/21/health/21flu.html  —Preceding unsigned comment added by 68.165.11.27 (talk) 02:16, 23 November 2009 (UTC)
thread_title:  Three waves seen to 1918 and 1957 influenza pandemics 

message: But the 1918 article, http://en.wikipedia.org/wiki/1918_flu_pandemic, reports it as 10-20%.
The 1918 article lists the percentage of the world's population that died as 1-3%, but of the 500 million infected, 50-100 million died.  — Preceding unsigned comment added by 157.185.37.93 (talk) 18:49, 14 March 2013 (UTC)
thread_title:  Mortality Rate of 1918 Pandemic listed as 2.5% 

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I have just modified 2 external links on Human mortality from H5N1. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20110727011806/http://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf to http://www.who.int/csr/disease/avian_influenza/Timeline_28_10a.pdf
*Added archive http://www.webcitation.org/5kCUlGdKu?url=http%3A%2F%2Fwww.cdc.gov%2Fncidod%2FEID%2Fvol12no01%2F05-0979.htm to http://www.cdc.gov/ncidod/EID/vol12no01/05-0979.htm
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thread_title:  External links modified 

message: Hello fellow Wikipedians,
I have just modified 6 external links on Human mortality from H5N1. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20060824004040/http://www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf to http://www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
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Cheers.—InternetArchiveBot (Report bug) 01:51, 27 March 2017 (UTC)
thread_title:  External links modified 

message: Hello fellow Wikipedians,
I have just modified 13 external links on Human mortality from H5N1. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20070629070846/http://www.lib.cau.edu.cn/qlga/86a.pdf to http://www.lib.cau.edu.cn/qlga/86a.pdf
*Added archive https://web.archive.org/web/20080117092338/http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_01_15/en/index.html to http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_01_15/en/index.html
*Added archive https://web.archive.org/web/20070416052840/http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_12_27/en/index.html to http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_12_27/en/index.html
*Added archive https://web.archive.org/web/20080128112145/http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_01_24/en/index.html to http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_01_24/en/index.html
*Added archive https://web.archive.org/web/20080530005232/http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_04_30/en/index.html to http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_04_30/en/index.html
*Added archive https://web.archive.org/web/20070527131033/http://www.who.int/csr/disease/avian_influenza/country/cases_table_2007_05_24/en/index.html to http://www.who.int/csr/disease/avian_influenza/country/cases_table_2007_05_24/en/index.html
*Added archive https://web.archive.org/web/20090515074918/http://www.acsh.org/factsfears/newsID.685/news_detail.asp to http://www.acsh.org/factsfears/newsID.685/news_detail.asp
*Added archive https://web.archive.org/web/20070629070843/http://www.wpro.who.int/NR/rdonlyres/299B9BDC-67D8-40AC-81BE-0BC8D38E296A/0/S2_0814.jpg to http://www.wpro.who.int/NR/rdonlyres/299B9BDC-67D8-40AC-81BE-0BC8D38E296A/0/S2_0814.jpg
*Added archive https://web.archive.org/web/20081119194526/http://www.wpro.who.int/NR/rdonlyres/FD4AC2FD-B7C8-4A13-A32C-6CF328A0C036/0/Slide4.jpg to http://www.wpro.who.int/NR/rdonlyres/FD4AC2FD-B7C8-4A13-A32C-6CF328A0C036/0/Slide4.jpg
*Added archive https://web.archive.org/web/20090115170040/http://www.pandemicflu.gov/plan/panflureport6.html to http://pandemicflu.gov/plan/panflureport6.html
*Added archive https://web.archive.org/web/20070309203425/http://www.seniorjournal.com/Spotlights/FLU2005-06/5-06-24PandemicProjections.htm to http://www.seniorjournal.com/Spotlights/FLU2005-06/5-06-24PandemicProjections.htm
*Added archive https://web.archive.org/web/20080827215244/http://www.wpro.who.int/NR/rdonlyres/7549914F-5C83-4418-8C20-007ADCC07C61/0/s3.jpg to http://www.wpro.who.int/NR/rdonlyres/7549914F-5C83-4418-8C20-007ADCC07C61/0/s3.jpg
*Added archive https://web.archive.org/web/20060423065725/http://www.who.int/csr/disease/avian_influenza/country/en/ to http://www.who.int/csr/disease/avian_influenza/country/en/
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Cheers.—InternetArchiveBot (Report bug) 11:36, 6 April 2017 (UTC)
thread_title:  External links modified 

message: Hello fellow Wikipedians,
I have just modified one external link on Human mortality from H5N1. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
*Added  tag to https://news.yahoo.com/s/nm/20080415/hl_nm/birdflu_japan_dc
*Added archive https://web.archive.org/web/20080827215244/http://www.wpro.who.int/NR/rdonlyres/7549914F-5C83-4418-8C20-007ADCC07C61/0/s3.jpg to http://www.wpro.who.int/NR/rdonlyres/7549914F-5C83-4418-8C20-007ADCC07C61/0/s3.jpg
When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.
Cheers.—InternetArchiveBot (Report bug) 15:56, 13 September 2017 (UTC)
thread_title:  External links modified 

message: Hello fellow Wikipedians,
I have just modified 2 external links on Human mortality from H5N1. Please take a moment to review my edit. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit this simple FaQ for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20071007194340/http://www.bloomberg.com/apps/news?pid=10000080&sid=aWESsJvt6CFE&refer=asia to https://www.bloomberg.com/apps/news?pid=10000080&sid=aWESsJvt6CFE&refer=asia
*Added archive https://web.archive.org/web/20081211175414/http://www.bloomberg.com/apps/news?pid=10000080&sid=a7CJ0uPPpg.g to https://www.bloomberg.com/apps/news?pid=10000080&sid=a7CJ0uPPpg.g
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Cheers.—InternetArchiveBot (Report bug) 14:22, 8 November 2017 (UTC)
thread_title:  External links modified