Talk:Transmission and infection of H5N1

== Implications of the PNAS study for eventual pandemic lethality -- Please help prepare this stub for inclusion in the main article ==

The recent PNAS study 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.

A pandemic is 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 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 the genes for the H5 and N1 receptors that the human immune system cannot yet recognize, resulting in a pandemic, because the 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 avian H5N1 infections have been in humans, as mild as a seasonal influenza, or something in between 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 one or two others. Lethality to humans is, however a matter of considerable interest to humans as we try to assess our risks.

In the recently completed PNAS study, hybrid influenza viruses were created in biosecure laboratories by combining avian H5N1 influenza from Indonesia with 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 PNAS 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 the PNAS 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, hence no less lethal than the Indon05 virus from which they were reassorted. Emergence of a 100% deadly virus that causes high URI titers may be the buried headline of the PNAS study. The reassortant PNAS 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.

Against the failure of a less-lethal virus to emerge in reassortment and the fact that high URI titers were observed, the fact that the ferrets in the next cage in the PNAS study were not infected is cold comfort indeed.

Although influenza viruses may be nearly indifferent to lethality as they emerge, with evolutionary pressures focused solely or principally on transmissibility and unrecognizability by host immune function, selection pressures may begin to be brought to bear once a pandemic that destroys its host becomes efficient in transmission. A very lethal pandemic that causes obvious symptoms may kill its hosts before they have the opportunity to infect many other potential hosts. 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. When it first emerged in late 1917 or early 1918, it was so mild as to be called the "three day flu." An article in an Italian medical journal questioned whether it was a flu at all. Unfortunately, the Spanish flu then apparently picked up a set of genes coding for lethality via a cytokine storm, and began the deadly wave that only afterward began to evolve toward milder effects. The prior history with the three-day flu may have given many in the human population the chance to develop at least some immunity, and increased their chance to resist the more lethal later wave when it emerged. 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 PNAS recombinants to exhibit reduced lethality is especially disappointing.

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)

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)

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)

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)

Breaking news: human-to-human transmission suspected in Indonesia

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)

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)