Talk:Transmission and infection of H5N1

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[edit] Which animals can be infected?

Hi, the article lacks information which animals can be infected. Could e.g. fish or rats get H5N1 as humans do? --Tobias Schmidbauer 14:16, 8 March 2006 (UTC)

Thanks for improving the article by noting that "human" was meant. Additional data on nonhumans would be an asset to the article, but as it stands now, that data is in related articles (see the H5N1 box at the top of the article). Transmission is currently wild birds and captive birds transmit H5N1 to wild birds and captive birds (with death rate in bird pecies ranging from near 0% to near 100% depending on the ird species), with an occational cat or human catching it and about half of those dying. The biggest issue is that it is STILL mutating, changing its characteristics, and adapting to an ever widening list of species that it being able to infect and kill in an unprecedented fashion that the experts find frightening, and governments are spending billions to research and come up with solutions to the problem. Mice are experimentally infected in laboratories, so I would guess rats could catch it too. Almost certainly not fish. The species H5N1 is a subtype of (Influenza A virus) attacks birds mainly, mammals secondarily. WAS 4.250 17:34, 8 March 2006 (UTC)

[edit] Maybe Wild birds are not so guilty?

Check out this report: Fowl Play: The Poultry Industry's Central Role in the Bird Flu Crisis -- an EXCELLENT 19-page report from a non-govt agency, that discusses in detail how the H5N1 virus originated in the intensive environment of factory farms, not backyard flocks, and is being spread by the commercial poultry industry, NOT by wild birds. Instead, wild birds are getting it from the wastes generated by commercial farms (such as the practice of using bird manure as fish food in China.) According to this report, the flu is NOT following the routes of migratory birds but, rather, it follows the roads and railways along which the industry transports its poultry. (Wild birds migrate north-south, NOT east-west, so how would they spread flu from China to Europe?) Some mention of this should be in the article. I will link the report. Rooster613 04:26, 10 May 2006 (UTC)Rooster613

Our H5N1 articles already have it right that the main spread is through commercial practices but that migratory birds play a significant role especially in continent to continent movement. However minor tweeking of individual paragraphs can be useful, so i won't prejudge what you may hope to contribute. But the debate between advocates goes at H5N1 impact in its political section. WAS 4.250 13:55, 10 May 2006 (UTC)

[edit] Sexual contact

Just for reference, I spent quite some time trying to find a reference for 68.91.114.193's comments re avian flu spreading among birds by sexual contact. I wasn't able to find anything. That doesn't, of course, mean that there's nothing to be found, but someone who's more familiar than I am with the literature will have to look. On the other hand, it might be worth stating in the article that much of the bird-to-bird transmission of H5N1 does happen via mating grounds, whether or not in the actual act of mating itself. That, at least, is well attested. Waitak 08:23, 28 May 2006 (UTC)

Bird to bird transmission of Influenzavirus A varies with the species of bird and the strain and subtype of virus with each bird species carrying different strains and subtypes, each bird species having differing pathogenetic profiles for each strain, and mostly undocumented transmission route profiles. We have no business saying anything that the experts don't say. There is simply way too much that is not known to draw our own conclusions from what is known. And in applying all this to H5N1, the experts are only saying "fund additional studies because no one knows enough to make good guesses on the future behavior of H5N1". WAS 4.250 13:54, 28 May 2006 (UTC)
In case it wasn't evident, I was agreeing with you... :-) Waitak 14:02, 28 May 2006 (UTC)
You said it might be worth stating in the article that much of the bird-to-bird transmission of H5N1 does happen via mating grounds. I don't know of a source where a qualified expert says this has any significance with regard to Transmission and infection of H5N1. For example, I had assumed different subtypes of avian flu virus were endemic in different species because of genetic factors as well as "birds of a feather flock together". If sexual behavior (Is it limited one's own species. Do birds engage in "beastiality" or bi-species sexual behavior? I read somewhere caged birds masturbate if they have no partner. I bet male birds will hump what's available.) is important in maintaining species specific strains, that would indeed be noteworthy. WAS 4.250 14:35, 28 May 2006 (UTC)

Ah, I see. I don't think I was clear enough, then. What I mean was that birds come together in great numbers during the mating season. This necessarily means that birds are in close contact with each other, more then than at any other time. Thus, no matter what the actual infection route is, it happens a lot more on the mating grounds than anywhere else, just because of the sheer physical proximity of many thousands of other birds. That much has been well attested, leaving completely aside the question of sexual contact. Hope that's clearer. Waitak 14:57, 28 May 2006 (UTC)

Yes, where ever birds gather. Whether for sex, for food, for water, for shelter, to sleep. The UN wants African nations to restore wetlands so wild birds don't congregate at the watering holes used by domestic birds and thus facilite wild bird to/from domestic bird H5N1 transfer. When I read that (the source is used in one of these articles, I can did it up if you wish) I thought good grief, African nations aren't even feeding their own humans and you expect them to increase the national resources that are set aside for wild life???? WAS 4.250 16:06, 28 May 2006 (UTC)
Without rereading the source, I believe I read the above here: SCIENTIFIC SEMINAR ON AVIAN INFLUENZA, THE ENVIRONMENT AND MIGRATORY BIRDS ON 10-11 APRIL 2006 published 14 April 2006.International Institute for Sustainable Development (IISD) WAS 4.250 16:15, 28 May 2006 (UTC)
The best on the subject is European Food Safety Authority (2006-04-04). title is "Scientific Statement on Migratory birds and their possible role in the spread of highly pathogenic avian influenza." (PDF format). A conference in a couple days (May 30-31?) in Europe (Italy?) is supposed to update it, if I remember correctly. WAS 4.250 16:31, 28 May 2006 (UTC)

[edit] Maintaining graphs

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)

Maybe if you asked around you could find a way to automate the process. Computers should be good for that sort of thing. WAS 4.250 11:43, 29 May 2006 (UTC)
Seems that way, doesn't it? I was hard pressed to think of one, though, and this is sort of what I do in life... very open to suggestions, though! The problem is that I'd spend t hours building something to save myself 15 minutes × k, and k has to be pretty big to make it worth the time I'd spend. Waitak 12:25, 29 May 2006 (UTC)
User:Eloquence comes to mind. You may wish to learn a little about him, then maybe ask him for a suggestion. You might even end up with a job offer at some point in your friendship with him. Just a thought. WAS 4.250 12:34, 29 May 2006 (UTC)

[edit] Human-to-human transmission


This story is developing - please help us to keep track of it over on Wikinews. We'd especially appreciate anyone vaguely scientific who can help us make sense of the story as it develops. Thanks Frankie Roberto 14:53, 3 June 2006 (UTC)

[edit] Footnotes in this article do not work

On July 2, clicking on footnotes in this article does not provide access to footnote content. Scrolling to the footnote area reveals html formatting and text.

Will a technically-inclined stalwart please take a look at the problem?

—The preceding unsigned comment was added by 67.101.69.139 (talk • contribs) .

Done. Waitak 04:59, 3 July 2006 (UTC)

[edit] Predicting pandemic lethality - genes 1

Please help prepare this stub for inclusion in the main article.


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.

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

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)

A succinct summary of the cover-up of the "Spanish" flu by warring governments during WWI appears in the first paragraph at http://birdflubook.com/a.php?id=2 That accounts of the progress of the deadly form was censored when it appeared in combatant countries, however, is no proof that an earlier, mild form did not circulate, as set forth by Parsons in "The Spanish Lady and the Newfoundland Regiment." http://www.vlib.us/medical/parsons.htm | W. David Parsons, MD, C.M., FRCP (C)

Could you do me a favor? This is intended to cover much of the background you covered above and you write so much better than I do. Could you please use your writing skills to improve this with much of the above content? Thanks ever so much. WAS 4.250 17:59, 3 August 2006 (UTC)

[edit] User talk:67.101.68.164 -- genes involved in lethality

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)

Very, very interesting. Assuming that various other genes are involved, does that yet shed any light on the likelihood of rapid or slow evolution to human contagion, or for predicting the greater or lesser likelihood of a rather lethal human-adapted influenza? - unsigned
Not yet it doesn't. So far the data shows it is more complex than we can yet analyse. Computer simulations and direct gene manipulation have yielded inconclusive results to the key questions you just asked; so more studies are ongoing in not only those areas but also:
  • bird species susceptibility
  • bird migration paths
  • cell based vaccine development
  • adjuvant testing
  • human vaccine clinical trials
  • bird vaccine testing and use
  • computer simulations of pandemic spread patterns (e.g. will grounding flights help?)
  • detailed shape and gene code analysis of each of the RNA stands for as many flu virus strains as possible and making them available on a database for study
  • wild bird testing for flu viruses
  • testing humans for asymptomatic H5N1 infection
  • training exercizes in case of a pandemic WAS 4.250 21:40, 8 December 2006 (UTC)

[edit] Vietnam contributed to low worldwide death rate in 2005

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)

[edit] WHO Definitions of a "Case" of H5N1

The case fatality ratio is the total deaths from WHO-confirmed cases, divided by the total of WHO-confirmed cases. the WHO has published specific criteria [4] that must be met before it confirms a patient's illness as a "case" of H5N1. The World Health Organization's newly published descriptions include specifications of what is meant by 'suspected', 'probable', and 'confirmed' cases of human H5N1 infection (Source: WHO).

[edit] Help, footnote 41 throws off self and rest of footnotes

Help, footnote 41 throws off self and rest of footnotes. —preceding unsigned comment by 67.101.66.14 (talk • contribs)

Fixed. The problems were:
  • the {{cite journal}} wasn't closed, so didn't render
  • there was a <ref> inside a <ref>, which isn't allowed. - Waitak 06:10, 27 October 2006 (UTC)

Thanks for fix and feedback!


[edit] Scientific advances may attenuate probable lethality

The genetic lethality potential of the initial pandemic strain is only one important factor in determining the ultimate outcome in number of human lives lost. Another factor that grows potentially more important with the passage of time is human preparation. For example, no vaccine specific to H5N1 could be produced when it emerged in Hong Kong in 1997, because it was lethal to eggs. Reverse DNA techniques have since made a vaccine possible, and several H5N1 vaccines have been tested and are in production in at least limited quantities. Vaccine development and production facilities are being ramped up, and possible pre-pandemic vaccines are being produced and studied. If a human pandemic does not emerge in the next few years, its eventual emergence may become almost a non-event if a very-effective pre-pandemic vaccine has prepared the population with sufficient herd immunity to blunt its lethality. Indeed, if there is sufficient immunity to stop it at the source, it will not become pandemic, but the first of a new class of viruses, a potential pandemic virus. The naivete of human immune function on which emergence of a pandemic appears will no longer be there. If the human population is thoroughly prepared, most novel potential-pandemic viruses will probably never be studied, because nobody will become sick enough with one to seek medical care and be tested.

As long as the likelihood of protecting the population continues to rise with the passage of time, that likelihood becomes an increasingly important factor in predicting the loss of lives and the amount of economic dislocation that will ultimately occur.

In light of human potential to develop herd immunity via vaccination in advance of a pandemic strain, the time that it allows us to do so before it evolves may become as crucial or more crucial to the measure of damage it causes than its own lethality and contagiousness. —The preceding unsigned comment was added by 67.101.68.3 (talk) 15:36, 8 December 2006 (UTC).

Absolutely true and well said. I think I'll add it to the article. WAS 4.250 21:48, 8 December 2006 (UTC)

[edit] Q: Can you get it from eating sick chickens? A: Yes!

CAN U CATCH AVIAN FLU FROM EATING INFECTED CHICKENS? —The preceding unsigned comment was added by 143.248.131.26 (talk) 03:17, 28 December 2006 (UTC).

Yes, you can catch avian flu from eating infected chickens. But fully cooking kills the virus, so it is contact with or eating uncooked or poorly cooked birds that is the problem. Preparing dead infected birds for eating is the most common way people catch avian flu. For example, the US imports fully cooked chickens from China but not uncooked chickens from China because of this. WAS 4.250 08:10, 28 December 2006 (UTC)
THIS IS NOT THE PLACE TO ANSWER QUESTIONS. Delete it please User:WAS 4.250 or include it in the main article. Pablo2garcia 17:40, 5 February 2007 (UTC)

[edit] Pervasive clinical testing bias skews understanding of H5N1

Selective clinical testing for H5N1 complicates the task of estimating its actual pervasiveness and lethality. It also makes it more difficult to determine whether there are vectors other than birds, e.g., cats.

In the countries where H5N1 is endemic, the vast majority of persons presenting themselves for medical treatment do not have H5N1. They have something else that presents with similar symptoms, perhaps dengue. Thus doctors screen persons with flu-like symptoms to determine what if any medical testing should be done. Depending on the symptoms and the alertness of the practitioner, the diagnostic interview may (or may not) include a question about whether the patient has seen, handled, or eaten poultry that was sick or that died of natural causes. If the patient has, H5N1 is likely to be suspected and tested for. If not, another of the many conditions things that can cause flu-like symptoms is more likely to be tested for, or perhaps no tests will be done. In any case, there will virtually never be any questions about exposure to cats or other possible vectors (even though a recent Indonesian test of 500 street cats found that 100 had H5N1 antibodies[5] [6]'Cat owners at risk of bird flu' (Daily Mail UK - 24th January 2007)</ref> -- and these cats were subsequently released alive back onto the streets).

The natural tendency of medical practitioners to focus on the most likely causes of illness has several results that skew the data available to epidemiologists.

First, assuming that only persons exposed to sick poultry will be tested for H5N1 infection, it follows that all positive test results for H5N1 infection will be found to have occurred among persons exposed to sick poultry. This implies that if and when another manner of H5N1 transmission emerges (such as pig- cat- or human-to-human transmission) the current usual limited diagnostic testing patterns will most often overlook it. To the extent that testing occurs only where avian transmission has likely occurred suggests that if and when mammalian transmission begins, it is likely to be discovered by testing only when exacerbating factors have already occurred, such as when an outbreak has already become widespread or a series of family members or associates has already fallen seriously ill or died. We will be very lucky indeed if, before any obvious human clustering or sequential illness emerges an exceptionally astute practitioner is somehow intuitive enough to test for and find the earliest human-to-human contagion, since the usual expected bird connection will be lacking. Instead, mild human cases with no bird contact seem almost certain to be missed, even if a lot of people present with them.

Second, if H5N1 is already being transmitted in apparently healthy mammals, such as in cats, pigs, or in humans that do not appear terribly sick or in any event are never tested, this as-yet unrecognized mammalian form may be less lethal than the direct avian-to-human contagions that are currently recognized and tested for. Once it crosses into mammals, viral evolution drives toward forms ever more benign to mammals. Infected mammals that live longer and can remain active have more chances to pass a virus on more effectively than bedridden or dead mammals. At the same time, mammalian-adapted virus variants are under obvious evolutionary pressure to become more easily human-contagious and which increases the chance that if there are mammalian and avian H5N1 lines circulating at the same time, the mammalian line is more likely to emerge as the first wave of a human H5N1 pandemic.

Finally, there is a circular relationship between the current testing bias and these skewed results it produces. The more practitioners test only persons with bird contact, the more the results suggest that bird contact is a necessary condition for bird flu to cause illness. And the more the general impression is that H5N1 infection is found only in persons who have had contact with sick birds, the less likely general practitioners will be to screen patients who do not report such contact.

—The preceding unsigned comment was added by 67.101.68.43 (talk) 17:37, 21 January 2007 (UTC).

To the extent that your concerns are warrented, the experts know about them and take them into account already. The experts' position is "we don't know" for many assertions that pass for fact in the general media. The H5N1 experts are currently concerned with the optimal expenditure of available time and money for the purpose of risk mitigation given the vast uncertainties involved. WAS 4.250 13:04, 22 January 2007 (UTC)

[edit] Global concern of bird flu to global warming

I think that we're worrying too much about little things that will last about 1-100 years, while global warming will take a longer time and can possibly pose a bigger threat. There will be NO birds if this continues. There will be less humans surviving the cancer rampant in the new atmosphere. There can be an cure to global warming compared to experimental drugs to a flu that constantly evolves. These points are my point of view. Someone take these into consideration. —The preceding unsigned comment was added by 76.81.177.144 (talk) 04:11, 9 March 2007 (UTC).

We are all dead in the long run. There is something to be said for acting on immediate concerns. WAS 4.250 08:11, 9 March 2007 (UTC)


[edit] WHO and news stories may both underreport current human H5N1 cases

The U.N. W.H.O. reports only 17 human H5N1 cases and 11 deaths for all of 2007 to March 19, 2007. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2007_03_19/en/index.html This is about half the number reported by the W.H.O. to March 12 of the year before. By March 12, 2006, the W.H.O. had reported 31 human H5N1 infections (16 more than in 2007) and 21 deaths (11 more than in 2007) up to March 12th of the year for those respective years.

A drop in 2007 to half the cases and deaths reported in 2006 would appear heartening if it were reliable, but the change may reflect that the U.N. figures are simply no longer as comprehensive in 2007 as they were 2006. For example at the end of January 2007 Indonesia stopped sending tissue samples of possibly human H5N1 infection patients to the W.H.O. In February up to March 19, 2007, the Indonesian press have announced confirmation in their laboratories of six additional human cases, with four additional deaths, but the W.H.O. could not confirm the cases in their labs and does not include them in the W.H.O. totals for 2007, as an article recently posted on CIDRAP discusses: http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/mar1907avian.html It is expected that if Indonesia later provides samples from the cases it has announced in February and March of 2007, official W.H.O. world totals will jump.

An unofficial total maintained by volunteers seems to reflect an increase in human H5N1 cases in 2007 up to March 12, 2007, of 23 new human infections including 14 deaths. These figures are derived from comparison of cumulative totals available of cases reported by the end of 2006 and by March 12, 2007, available at CurrentEvents.com. These tables show that at the end of 2006, 288 total human H5N1 cases, and 159 deaths had been reported. [3] On March 12, 2007, the current figures from the same source were 311 human cases (an increase of 23 in 2007 from the 288 at the end of 2006) and 173 deaths (an increase of 14 in 2007 from the 159 reported by the end of 2006). [4]

Meanwhile, the W.H.O. figures for all of 2007 showed, on March 15, 2007, only 15 cases, including 10 deaths. If the news reports are right, then the official W.H.O. figures overlook at least 9 cases in 2007 (23 less 15) and at least 4 deaths (14 less 10). At least some of the cases overlooked by the U.N. would be the Indonesian cases.

The decision by the U.N. W.H.O. to report only what it can confirm in its labs is not the only factor that limits the comprehensiveness of the W.H.O. count. Countries lose money from tourist and poultry trade when lethal H5N1 breaks out. As large human clusters of lethal H5N1 broke out in Turkey in the Spring of 2006, ordinary Turks were far more worried about loss of Russian tourism than about H5N1. In 2007, the Turkish government has taken extraordinary measures consistent with outbreaks, but reported no cases. This, and similar actions by other countries, may reflect that governments around the world are under considerable pressure to prevent the press from reporting that H5N1 has broken out, whether it has or not. In at least some countries, it is likely that an official or unofficial curtain of censorship is falling, resulting in fewer cases being reported in the world press. If so, that censorship would include withholding samples from the W.H.O. without the country necessarily announcing that it is doing so, further undermining the comprehensiveness of the W.H.O. reported figures.

An exceptionally telling series of incidents were recently collected by a well-regarded blogger (a medic by training) noting press reports give telling indications that in a number of countries the governmental authorities took extreme steps consistent with the occurrence of a serious outbreak, including sweeping quarantine and security measures. In this context, reports on the results of H5N1 testing would be expected, and instead comes ... nothing. Beyond attenuating the usefulness of the W.H.O. purposes, his failure for of the other shoe to drop via press followup deprives the public of the press reports that it relies on to gauge the seriousness of the H5N1 threat. Perhaps as a result there is a growing gap between the general public and experts in the spread of the epidemic, who decry the press going silent and resultant unconcern of those who rely on it.

Lack of cooperation of Indonesia and other countries, and recent notable incidents the absence of press reports following signs of quarantine and security measures by authorities consistent with a serious outbreak, was noted in some detail on March 15 at "Avian Flu Diary" http://afludiary.blogspot.com/ as follows:

Whatever Happened To . . . ?

Tomorrow I'll be leaving for a week to make my thrice annual road trip to see my doctor in Missouri, and will be offline and unable to blog for most of that time. I will try to get an update in every few days, but will be working off of a laptop and dealing with slow dialup connections while on the road.

I'd hoped that, before I left, we'd have some answers to some of the open stories of the past few weeks. Unless we see a flurry of news reports in the next 24 hours, that isn't likely to happen.

From the `pending' file, we are still waiting to hear whatever happened to . . .

  • Korea: A week ago we were informed they had a suspected human case of H5N1 infection. A few hours later, it was intimated the patient might have meningitis instead. Tests were pending. Since then, not a word.
  • It doesn't take a week to rule out meningitis, and it certainly shouldn't take a week to confirm H5N1. This is South Korea, a country not devoid of technology or medicine, and so they ought to know by now what they are dealing with.
  • A simple LP (Lumbar puncture) would yield spinal fluid which in an hour would tell them if the patient had an elevated white count, a sure sign of meningitis. Lab cultures might take 72 hours to further define the type of infection. PCR blood testing should have revealed if the patient has the H5N1 virus by now.
  • China: On February 28th, we learned of a 44-year-old woman named Li who was diagnosed with the H5N1 virus. On March 5th, we heard she was being treated with an experimental serum made from the blood of a previously recovered patient. Since then, I've seen no reports on this patient.
  • At roughly the same time, Chinese officials took umbrage over the conclusions of a study naming Guangdong Province as origin of the H5N1 virus. One can't help but wonder if the lack of news, and the offense taken by the Chinese aren't somehow related.
  • Iran: Not a surprise really, as Iran isn't exactly a fountain of information to the west, but we've heard nothing since March 7th about a die off of birds at Tehran’s Pardisan Park, purportedly attributed to an outbreak of avian flu.
  • The chairman of environmental NGO Avay-e Sabz (Green Song) Society called on citizens, especially children to avoid visiting the park until the results of laboratory examinations on carcasses of 24 saker falcons, one kestrel and a number of owls were revealed.
  • Turkey: During the month of February we heard multiple reports of villages quarantined, and massive culling operations going on. Paramilitary guards were posted to keep people, and poultry, from exiting the area. A number of people were being tested for `suspected' avian flu infection.
  • Since then, I can't find any news on these outbreaks. I have no idea if the quarantine has been lifted. The last OIE ( World Organisation for Animal Health) report is dated March 1st, 2007, and lists 17 outbreaks in Turkey as `unresolved'.
  • Vietnam: A week ago residents in some suburbs of Hanoi were told they could not leave their homes unless they were wearing masks due to concerns over the transmissibility of the H5N1 virus. Media reports spoke of quarantines, military checkpoints, and multiple outbreaks in poultry.
  • Indonesia: Last weekend it was announced they had a 20-year-old woman positive for the H5N1 infection. Since then, no new word on her condition. With the ongoing tension between the WHO and the Indonesian Health Minister over vaccines, the WHO hasn't had an update on Indonesia in since January 29th.

These are just some highlights of course. There are many stories that appear, only to be lost somehow in the shuffle.

Some days it seems like we get no news, and that nothing is happening. The media moves on to other `important' stories, like Anna Nicole Smith, or the latest entrant into a presidential race still 18 months away. Bird flu falls off the radar.

But obviously there are things going on, we just don't always hear about them.

posted by FLA_MEDIC @ 6:03 AM 0 comments

(above provided by 67.101.68.222 )

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