Avian Flu Pandemic?

[Adrian]

I have just begun to go through the data surrounding H5N1. Does anyone know any more about the specific rates of cross-species transfer? The numbers from WHO do not seem to justify the great hype surrounding the "impending doom". Here are the WHO mortality numbers:


26.12.03-10.03.04: 35 cases, 24 deaths
19.07.04-08.10.04: 9 cases, 8 deaths
16.12.04-to date: 72 cases, 28 deaths
TOTAL: 116 cases, 60 deaths

(Source: WHO, Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO, Sep 2005)

The numbers just seem to warrant such a large focus. Much of the deaths have been because of people handing dying and diseased birds, or people cleaning bird droppings. The WHO paper on the topic ("Assessment of risk to human health associated with outbreaks of highly pathogenic H5N1 avian influenza in poultry", WHO 2004) states that the high risk areas tend to be open-air markets in low income areas. It doesn't seem that it would be that difficult to spend a few million to ensure more sanitary conditions, but I have been hearing estimates of spending over 60 million dollars in US alone. I guess they are worried about a mutation, but WHO's own recommendations seem a little overkill: "Rapid destruction – within three days – of Hong Kong’s entire poultry population, estimated at around 1.5 million birds" (Avian influenza, WHO 2004).

Does anyone have any more data on the subject?

 

[TobiasTheViking]

If they didn't make statements like that(which they do all the time, remember SARS?) then you would never hear about them.

And nothing would be done. It is a game of "Cry Wolf" where you need to do it to get any funding to work with the problems that are real(and just general funding to run the program). And you have to "Cry Wolf" to get the funding, in the end, it will probably bite them, but that is what they are doing.


What is that i'm hearing, uh, a branch broke THERE IS A WOLF.
Oh, i guess not anyways, just a deer.
What is that i'm hearing, uh, a branch broke THERE IS A WOLF.
oh, i guess not anyways, just a cow.

etc.

Of course, i may be pesimistic.

 

[drkitten]

I have just begun to go through the data surrounding H5N1. Does anyone know any more about the specific rates of cross-species transfer? The numbers from WHO do not seem to justify the great hype surrounding the "impending doom". Here are the WHO mortality numbers:

The numbers just seem to warrant such a large focus.

Yes, it's a mutation that they are worried about.

Specifically, they're worried about a mutation that will enable human-to-human transfer. So far, (almost) all cases in humans have been incurred directly from birds. I think there are like three cases of human to human transfer on record, and no recorded cases of a human-to-human-to-human transfer.

However, influenza, in general, is one of the most infectious diseases out there, which is why it's so easy to catch (from other humans). The influenza virus is also known to swap genes between subtypes. As soon as the H5N1 virus acquires the ability to be transferred easily from human to human -- and it's a question of when, not if -- we're quite possibly going to see a billion cases wordwide, as people in Hong Kong pick it up and carry it via airplane literally all over the world. With a 50% mortality rate, that could kill 500 million people.

Basically, it's a time bomb, and the pathologists can hear it ticking.

 

[Adrian]

Yes, it's a mutation that they are worried about.
However, influenza, in general, is one of the most infectious diseases out there, which is why it's so easy to catch (from other humans). The influenza virus is also known to swap genes between subtypes. As soon as the H5N1 virus acquires the ability to be transferred easily from human to human -- and it's a question of when, not if -- we're quite possibly going to see a billion cases wordwide, as people in Hong Kong pick it up and carry it via airplane literally all over the world. With a 50% mortality rate, that could kill 500 million people.

I just don't get the logical jump from 110 cases to a billion? There have been human cases of H5N1 even before 1997 and it has not yet mutated into a human-to-human disease. It is true that this variant has a propensity to mutate quite often, but there are quite a few diseases that share this propensity that have not become global pandemics. High mutation rates do not necessarily mean global pandemic and such "end of times" outcomes.

 

[Kevin_Lowe]

I do not imagine anyone has a scientifically based idea on exactly how likely it is for H5N1 to mutate into a pandemic killer, owing to the lack of data on such things.

We do know that the possibility is real, however, and the consequences would be disastrous.

 

[Dymanic]

Adrian:
It is true that this variant has a propensity to mutate quite often, but there are quite a few diseases that share this propensity that have not become global pandemics.

It doesn't have to be a mutation. The big concern is that H5N1 will gain the capability for human-to-human transmission through recombination with another strain.
http://www.recombinomics.com/News/10050503/1918_Recombination_Confirmed.html

You are right that H5N1 isn't the only pathogen capable of producing a global pandemic; it's just the one to watch right now. It is also true that until the new strain emerges, we can't acurately predict what the attack rate will be, but it is not unreasonable to expect something like 15% to 35%. Let's hope the death rate is closer to the 1% or 2% seen in typical flu strains than to the over 50% we're seeing in the current strain.

It may not be possible to be completely prepared for such an event, but that doesn't mean we have to be as completely unprepared as we are at present.

Kevin_Lowe:
I do not imagine anyone has a scientifically based idea on exactly how likely it is for H5N1 to mutate into a pandemic killer, owing to the lack of data on such things.

Perhaps not exactly how likely, but it is reasonable to say -- approximately -- that it is very likely.

Two types of molecules project from the surface of a virus: a hemagglutinin and a neuraminidase (hence, "H5N1", etc). The hemagglutinin binds to carbohydrate on the glycoproteins of the epithelial cells of the host; the neuraminidase facilitates the budding of fresh virus from the plasma membrane. To survive, the virus must (because of the strong antibody response by the host's immune system) constantly change the epitopes on the hemagglutinin molecule. It's called antigenic shift, and it's what flu viruses do.

--------------------------
"The differences between 2004 H5N1 from Vietnam and 2005 H5N1 from Qinghai Lake are 18 amino acids in HA and 13 amino acids in NA. Thus, the number of differences between H5N1 in 2004 in Vietnam and 2005 in Qinghai Lake is almost as great as the number of differences between 1997 and 2004, which covers 7 years."
--------------------------
http://www.recombinomics.com/News/08060504/H5N1_Vaccine_Evolution.html

 

[Badly Shaved Monkey]

The unspoken assumption in the doomsday scenarios is that it acquires human-human transmissibility and retains its high pathogenicity. I don't know what the odds are and I've not seen it discussed.

 

[Bowser]

The current mortality rate isn't 50%. That is the rate of the sickest people who landed in the Asian health facilities. It doesn't account for those who never really manifested any symptoms or recovered on their own.

One of the issues is, being bird flu, it will be very difficult to produce much vaccine, and it will take a while to produce any. If h5n1 hits here this winter, we won't have any vaccine. Meanwhile, China's "husbandry" practices are ensuring that h5n1 will become increasingly resistant to the few available pharma anti-virals. The one that has been most highly lauded, Tamiflu, is in seriously short supply. At least for those of us in the U.S. since the major national order is on long backorder.

Another issue is that this isn't ordinary flu. It is a superflu that can kill otherwise healthy individuals (young adults) by cytokine storm.

To the extent the 1918 Spanish Flu was "doomsday", it had a relatively low mortality rate, but spread quickly and killed very quickly. Flu doesn't need a high mortality rate to be very disruptive.

 

[Badly Shaved Monkey]

The current mortality rate isn't 50%. That is the rate of the sickest people who landed in the Asian health facilities. It doesn't account for those who never really manifested any symptoms or recovered on their own.

One of the issues is, being bird flu, it will be very difficult to produce much vaccine, and it will take a while to produce any. If h5n1 hits here this winter, we won't have any vaccine. Meanwhile, China's "husbandry" practices are ensuring that h5n1 will become increasingly resistant to the few available pharma anti-virals. The one that has been most highly lauded, Tamiflu, is in seriously short supply. At least for those of us in the U.S. since the major national order is on long backorder.

Another issue is that this isn't ordinary flu. It is a superflu that can kill otherwise healthy individuals (young adults) by cytokine storm.

To the extent the 1918 Spanish Flu was "doomsday", it had a relatively low mortality rate, but spread quickly and killed very quickly. Flu doesn't need a high mortality rate to be very disruptive.

Congratulations. Intelligent and interesting

 

[Dymanic]

The unspoken assumption in the doomsday scenarios is that it acquires human-human transmissibility and retains its high pathogenicity. I don't know what the odds are and I've not seen it discussed.

I don't see those as unspoken assumptions; if you haven't seen this discussed explicitly, you may simply not have looked in the right places. The question would seem to be: are those reasonable assumptions?

The human population has no known natural immunity to H5N1 because it is genetically distinct from the three flu strains currently circulating in humans (H1N1, H1N2, and H3N2). Because of this, high pathogenicity is pretty much a slam dunk for the virus once it attains human-to-human transmissibility; maybe not 55%, but still, high.

As for the liklihood of the virus aquiring the capability for human-to-human transmissibility, it's worth keeping in mind that the influenza virus genome has remarkable plasticity because of a high mutation rate and its segmentation into 8 separate RNA molecules. This segmentation allows frequent genetic exchange by segment reassortment in hosts co-infected with 2 different influenza viruses. It's really just a matter of time.

 

[Badly Shaved Monkey]

I don't see those as unspoken assumptions; if you haven't seen this discussed explicitly, you may simply not have looked in the right places. The question would seem to be: are those reasonable assumptions?

The human population has no known natural immunity to H5N1 because it is genetically distinct from the three flu strains currently circulating in humans (H1N1, H1N2, and H3N2). Because of this, high pathogenicity is pretty much a slam dunk for the virus once it attains human-to-human transmissibility; maybe not 55%, but still, high.

As for the liklihood of the virus aquiring the capability for human-to-human transmissibility, it's worth keeping in mind that the influenza virus genome has remarkable plasticity because of a high mutation rate and its segmentation into 8 separate RNA molecules. This segmentation allows frequent genetic exchange by segment reassortment in hosts co-infected with 2 different influenza viruses. It's really just a matter of time.

OK, not discussed where I have read about it, but your answer still hasn't answered my conundrum. Are human-human transmissibility virulence factors indpendent of pathogenicity?

 

[Capsid]

OK, not discussed where I have read about it, but your answer still hasn't answered my conundrum. Are human-human transmissibility virulence factors indpendent of pathogenicity?

I think it is not known. Nothing about the sequence of the 1918 Spanish flu virus indicated that it was pathogenic.

 

[Badly Shaved Monkey]

I think it is not known. Nothing about the sequence of the 1918 Spanish flu virus indicated that it was pathogenic.

Your definitive lack of definitiveness seems more reasonable to me than the simplistic predictions.

 

[Dymanic]

Are human-human transmissibility virulence factors indpendent of pathogenicity?

Well, since "virulent" and "pathogenic" may be regarded as synonymous, what you are asking is whether human-human transmissibility is independent of virulence/pathogenicity.

The answer (which may not help much) is: yes and no, and (as Capsid has pointed out) we don't know. Does the incomplete nature of our ability to predict the course and strength of an approaching hurricane render any attempts to do so 'simplistic'? We can't know exactly what changes are required to facilitate sustained human-human transmission, nor predict what other changes might accompany such a change. It is of course possible that in aquiring genes from another strain, H5N1 might lose enough of its virulence as to be no worse than a typical flu strain. A category 5 hurricane might also lose much of its strength before making landfall, but counting on that may not be the best bet either. Whatever is not clear, one thing that is is that the world is far less prepared to deal with a major pandemic of any type than was New Orleans to deal with Katrina.

 

[Badly Shaved Monkey]

Well, since "virulent" and "pathogenic" may be regarded as synonymous, what you are asking is whether human-human transmissibility is independent of virulence/pathogenicity.

The answer (which may not help much) is: yes and no, and (as Capsid has pointed out) we don't know. Does the incomplete nature of our ability to predict the course and strength of an approaching hurricane render any attempts to do so 'simplistic'? We can't know exactly what changes are required to facilitate sustained human-human transmission, nor predict what other changes might accompany such a change. It is of course possible that in aquiring genes from another strain, H5N1 might lose enough of its virulence as to be no worse than a typical flu strain. A category 5 hurricane might also lose much of its strength before making landfall, but counting on that may not be the best bet either. Whatever is not clear, one thing that is is that the world is far less prepared to deal with a major pandemic of any type than was New Orleans to deal with Katrina.

Small point, when I did microbiology, virulence factors and pathogenicity were different, hence my usage. Virulence factor is a more global term that includes transmissibility whereas pathogenicity specifically refers to the amount of damage done to the host.

 

[Nobody]

Has it been possible for the authorities to make a rough guess of when this virus will actually spread and cause a pandemic ? Earlier in the year I heard that it was expected to arrive round about now and that there would be a severe shortage of vaccine and anti-virals.

Has a vaccine against H5N1 been developed yet ? If this is the case, is it expected that enough will be ready to avoid spread of the disease to pandemic proportions ? Assuming pharmaceutical companies market Oseltamivir/Zanamivir at as fast a rate as possible, is it expected that there will be enough of these drugs available to treat/prevent infection in unvaccinated or already ill individuals ?

 

[TobiasTheViking]

Has it been possible for the authorities to make a rough guess of when this virus will actually spread and cause a pandemic ?

I don't think anyone have ever made a prediction like that, or rather, i don't think one have ever come true.

Please provide me with sources if i'm wrong.

 

[Nobody]

I don't think anyone have ever made a prediction like that, or rather, i don't think one have ever come true.

Please provide me with sources if i'm wrong.

It might just have been a rumour. I was just wondering if the virology experts had enough information yet to determine when the pandemic is likely to emerge and hence if there will be enough vaccine and anti-virals available to avert a massive scale disaster.

 

[TobiasTheViking]

It might just have been a rumour. I was just wondering if the virology experts had enough information yet to determine when the pandemic is likely to emerge and hence if there will be enough vaccine and anti-virals available to avert a massive scale disaster.

oh, theyve made many predictions, based on the information they have, and some made up numbers.

Just like you can prove with the same equation that.
1) there are thousands of other alien races living in our galaxy
2) we are most likely the only race in our galaxy.

We can do that because we don't know the numbers, so we guess. Well, they guess.

But i am eager to be proven wrong, since this is very pesimistic.

 

[Dymanic]

Has it been possible for the authorities to make a rough guess of when this virus will actually spread and cause a pandemic?

A rough guess? Sure: "Maybe soon".

Earlier in the year I heard that it was expected to arrive round about now and that there would be a severe shortage of vaccine and anti-virals.

The regular flu season in the northern hemisphere typically starts anywhere between now and a month or so from now, but as for avian flu, I don't know who would have been willing to stick their neck out far enough to make a specific prediction like that.

Has a vaccine against H5N1 been developed yet?

No. There's a bit of a problem with that. It has to do with economics. Drug companies operate on a for-profit basis, and developing and testing vaccines gets expensive. The fact that flu virus is genetically a moving target creates a real possibility that a manufacturer could get stuck holding large quanitites of useless product. The success of each year's flu vaccine is dependent on a mix of educated guesswork and luck, and that's with strains already in the human population. Without the support of public money, commercial enterprises couldn't afford to attempt development of a vaccine.

The NIH has paid Sanofi Pasteur and Chiron, a manufacturer based in Emeryville, California, to make prototype vaccines against H5N1, with the hope that these vaccines would confer at least some resistance against the new strain. They have reported some successful results against current strains of H5N1, but using dosages much higher than the 15 micrograms typical for flu vaccines. The U.S. awarded them a $100 million contract on Thursday, and they expect to report results on low-dosage tests by December.

If this is the case, is it expected that enough will be ready to avoid spread of the disease to pandemic proportions?

No. Once the new stain emerges, we're looking at probably six months to develop a vaccine (unless Sanofi Pasteur gets lucky). And even then, worldwide capacity for flu-vaccine production is currently only about 300 million doses per year (depending on whom you talk to, and what constitutes a 'dose').

is it expected that there will be enough of these drugs available to treat/prevent infection in unvaccinated or already ill individuals?

Treating and preventing are two very different things. A lot depends on how early an outbreak is identified, on how quickly authorities respond (and on just how much authority they are given) as well as on the availability of resources. If an outbreak was identified early enough, ill individuals could be treated with antivirals, but if it was already rolling, it might make better sense to use 'Draconian quarantine' of those already infected, allocating antivirals first to prophylactic treatment of emergency and health-care workers, etc. The trick is whatever works best to keep the 'R-naught' (or R0) number down; the average number of new infections that one infected person will cause.