In 6 months, 1 billion dead in avian flu?

[Aquamarine]

“Up to one billion people could die around the whole world in six months,” Lvov said. The expert did not give a timeframe for the epidemic, but said that it is highly probable that it will start this year. “We are half a step away from a worldwide pandemic catastrophe,” the academic said.

http://www.mosnews.com/news/2004/10/28/pandemic.shtml

Others are more optimistic:

Between a quarter and a third of the world's population will fall ill, according to new World Health Organization estimates, and 1 per cent of the sick will die.
Do the math and the numbers defy credulity; between 16 million and 21 million people would die in a matter of mere months.

http://www.theglobeandmail.com/servlet/story/RTGAM.20041117.wpan1117/BNStory/specialScienceandHealth/

Not that I understand how they get these optimistic number since avian flu has had a fatality of about 70% of those infected.

 

[russ_watters]

Not that I understand how they get these optimistic number since avian flu has had a fatality of about 70% of those infected.

Well, where does the Russian agency get 70%? I'd be more inclined to believe 1% - its "only" the flu.

[google...]http://www.dailytimes.com.pk/default.asp?page=story_9-2-2004_pg7_40 appears to be the source:

Up to 70 percent of people who have caught bird flu in the latest Asian outbreak have died from the virus, around twice the level in the 1997 outbreak in Hong Kong, a doctor from the territory said on Sunday.

“The data suggests it is in the range of 60 to 70 percent, so we are quite shocked by this,” said David Hui, specialist in respiratory medicine at the Chinese University of Hong Kong. “Last time, the mortality rate was 30 percent.”

One danger here is sample size - the 30% was 6 out of 18 (from another site). With that small of a sample, you can get a sample bias.http://www.globalaging.org/health/us/flu2.htm to remember about the flu - it kills roughly 36,000 people a year in the US and 90% are over age 65. I'm having trouble finding a death rate - probably because a significant fraction of cases go unreported.

 

[Aquamarine]

Many comments from a physician on Avian flu:
http://www.recombinomics.com/whats_new.html

His view on pandemic potential:
http://www.recombinomics.com/pandemic_potential.html

 

[Aquamarine]

But the WHO and CDC quotes much lower number and hopefully are more correct. Unless they are conservative and wants to avoid a panic.

The worst flu until now was probably the flu of 1918, which killed 20-50 million. A flu of similar severity could kill many more since world population has increased 3-4 times since that. But maybe better knowledge can give more effective countermeasures today. Hopefully vaccination could protect those in rich countries several months after an outbreak. There are some expensive anti-virals that also may help, especially as profylax, but also only a very small number of people initially. Probably restricted to health care professionals.

Large number of cases could overwhelm at least the health care system and maybe also other parts of society, for example food distribution. Especially from panic.

 

[niman]

Case Mortality Rate

But the WHO and CDC quotes much lower number and hopefully are more correct. Unless they are conservative and wants to avoid a panic.

The case mortality rate in the 70-80% is pretty solid. There were human cases in Vietnam and Thailand at the beginning of this year, and then another wave over the summer. All data sets have case mortaility rates in the 70-80% range.

The key question concerns human to human transmission. If the H5N1 virus just picks up the abilty to recognize human receptors via recombination

http://www.recombinomics.com/viral_evolution.html

the virus can achieve a high transmission rate and maintain the high case fatality rate (which is much higher than seen in the 1918 flu pandemic).

CDC and WHO are being VERY conservative (and optimistic) by assuming that the case fatality rate would fall from 70% to 1%.

 

[Aquamarine]

Welcome Niman.

Do you think it would be possible to quickly produce large amounts of a vaccine after an outbreak with new technologies? Assuming that the government will simply ignore all the usual hurdles like extensive safety testing and patent rights, if they slow the process?

http://www.upmc-biosecurity.org/misc/flu/vaccine.html
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=11803087

 

[arildno]

We shouldn't hold on to a too bleak perspective on this, as long as we steel ourselves to endure some harsh measures in the event of a pandemic without functional vaccines:

One tends to forget that tuberculosis in the Western world was successfully combated without really efficient vaccines:

What the health authorities did, was wide-spread use of quarantining infected individuals, and, by being efficient in this, were largely successful of containing outbreaks at manageable levels.

(Tuberculosis remains, however, one of the most widespread diseases today, particularly in 3rd world countries with inefficient local health authorities&restricted access to vaccines/antibiotics.)

If our health authorities (surgeon generals and the like) dare to implement the sufficient restrictions on peoples' movement (i.e, freedom), such a pandemic can be kept in check, even if we at present lack efficient medicines to combat the plague directly.

 

[niman]

New Vaccines

Welcome Niman.

Do you think it would be possible to quickly produce large amounts of a vaccine after an outbreak with new technologies? Assuming that the government will simply ignore all the usual hurdles like extensive safety testing and patent rights, if they slow the process?

http://www.upmc-biosecurity.org/misc/flu/vaccine.html
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=pubmed&dopt=Abstract&list_uids=11803087

The technologies exist not only for stockpiling vaccines, but also for predicting new isolates before they emerge

http://www.recombinomics.com/vaccine_development.html

but its easier to do on paper than scale up to make billions of vaccines.

 

[Aquamarine]

We shouldn't hold on to a too bleak perspective on this, as long as we steel ourselves to endure some harsh measures in the event of a pandemic without functional vaccines:

One tends to forget that tuberculosis in the Western world was successfully combated without really efficient vaccines:

What the health authorities did, was wide-spread use of quarantining infected individuals, and, by being efficient in this, were largely successful of containing outbreaks at manageable levels.

(Tuberculosis remains, however, one of the most widespread diseases today, particularly in 3rd world countries with inefficient local health authorities&restricted access to vaccines/antibiotics.)

If our health authorities (surgeon generals and the like) dare to implement the sufficient restrictions on peoples' movement (i.e, freedom), such a pandemic can be kept in check, even if we at present lack efficient medicines to combat the plague directly.

Influenza is a nightmare to try to quarantine. If I remember correctly an comparison between SARS and influenza, someone holding a lecture might infect a person right next to him with SARS. He might infect everybody listening in a large room with influenza.

Here is a map of the spread of the 1918 epidemic. Click on maps:
http://history1900s.about.com/gi/dynamic/offsite.htm?site=http%3A%2F%2Fwww.pbs.org%2Fwgbh%2Famex%2Finfluenza%2Ftimeline%2Findex.html

Today everything will go much quicker because of airplanes and cars. But I expect that closing of schools, public meetings, entertainment centers and so on will be tried. But that were also tried in 1918 but then there were also many mass gatherings after the war and when the soldiers returned. It will not be possible to stop people from meeting at work and in shops.

Here is an interesting paper that seem to indicate that very strong quarantine might be effective. (I have only read the free abstract):
http://www.pnas.org/cgi/content/abstract/0407293101v1?view=abstract

 

[niman]

Quarantine

We shouldn't hold on to a too bleak perspective on this, as long as we steel ourselves to endure some harsh measures in the event of a pandemic without functional vaccines:

One tends to forget that tuberculosis in the Western world was successfully combated without really efficient vaccines:

What the health authorities did, was wide-spread use of quarantining infected individuals, and, by being efficient in this, were largely successful of containing outbreaks at manageable levels.

(Tuberculosis remains, however, one of the most widespread diseases today, particularly in 3rd world countries with inefficient local health authorities&restricted access to vaccines/antibiotics.)

If our health authorities (surgeon generals and the like) dare to implement the sufficient restrictions on peoples' movement (i.e, freedom), such a pandemic can be kept in check, even if we at present lack efficient medicines to combat the plague directly.

The effectiveness of quarantine really depends of the organism. For SARS quarantine may have helped because peak levels of virus shedding was several days after symptoms (and seasonal factors may have played a fairly major role).

Flu can move around pretty quickly and there are some major issues regarding under devloped contires and rural areas

http://www.recombinomics.com/flu_laos_cambodia.html

I think flu, if human to human transmission is efficient, will be very tough to control by quarantine.

 

[Aquamarine]

Here is an interesting paper that seem to indicate that very strong quarantine might be effective. (I have only read the free abstract):
http://www.pnas.org/cgi/content/abstract/0407293101v1?view=abstract

The government seems to have similar thoughts :
http://www.sciencedaily.com/releases/2004/11/041116153511.htm

 

[iansmith]

What the health authorities did, was wide-spread use of quarantining infected individuals, and, by being efficient in this, were largely successful of containing outbreaks at manageable levels.

I just want to add that one simple sanitary measure was responsible for the decrease of the level of transmission of TB and other infectious microorganism. This measure is called pasteurization. Prior to pasteurization, milk was one of the major infection vector. The Cow TB could be pass to human by milk. This is a major problem in the underdeveloped countries.

The same thing can be applied to influenzae. The major cause of outbreak is bad sanitition at the farm level. Duck pass influenzae to pig or human, human or pig exchange the virus. Sanitation would the best way to go for now because most of the transmission is done via the duck-human path.

 

[Aquamarine]

I just want to add that one simple sanitary measure was responsible for the decrease of the level of transmission of TB and other infectious microorganism. This measure is called pasteurization. Prior to pasteurization, milk was one of the major infection vector. The Cow TB could be pass to human by milk. This is a major problem in the underdeveloped countries.

The same thing can be applied to influenzae. The major cause of outbreak is bad sanitition at the farm level. Duck pass influenzae to pig or human, human or pig exchange the virus. Sanitation would the best way to go for now because most of the transmission is done via the duck-human path.

How about killing all ducks? Setting a reward for each killed duck would be quite effective. We can keep some tucked away in zoos. Sure, they are probably important in the ecosystems for eating insects or something similar but that would seem to be a small price for stopping this catastrophe. Not to mention that they are also the silent carriers of the ordinary yearly flu which kills tens of thousands each year in the US alone.

 

[iansmith]

Killing all the duck might be an over-reaction. Duck are asymptomic carriers, except with some recent cases.

The problem with chinese farming is that the duck and the pigs are in close contact and the hygene level is below any statisfactory standard. The problem does not really exist in the americas and europe. The solution would be for the chinese government to educated their farmer and change their pratice. The pandemic will not occur if those simple rules are followed.

 

[Aquamarine]

Killing all the duck might be an over-reaction. Duck are asymptomic carriers, except with some recent cases.

The problem with chinese farming is that the duck and the pigs are in close contact and the hygene level is below any statisfactory standard. The problem does not really exist in the americas and europe. The solution would be for the chinese government to educated their farmer and change their pratice. The pandemic will not occur if those simple rules are followed.

The farmers in southeast Asia are still very poor and it may not be possible for them to separate their free-ranging tame birds from wild ducks. That and education would take a long time. Killing the ducks could be done quickly.

 

[niman]

Much has been made of pigs as a "mixing vessel". However, H5N1 has evolved considerably and it is not clear that a mammalian mixing vessel is required for H5N1 to achieve human to human transmission.

The most prevelent serotype in Asia is H9N2 and some H9s already have human receptor binding sequences. Moreover, some H5N1 isolates from dead patients grow assymptomatically in ducks, and the ducks excrete high levels of virus.

Thus, a dual infection involving H9N2 and H5N1 in birds could generate a recombinant with the high case mortality associated with H5N1 and human recptor binding properties seen in H9N2

http://www.recombinomics.com/H5N1_H9N2.html

Thus, a pandemic strain can evolve without pigs, humans, or high density farms and a little recombination can go a long way

http://www.recombinomics.com/pandemic_potential.html

 

[tumor]

Global pandemic will finish us all, not nukes.

 

[niman]

H5N1 Mating and Mutating

Today Reuters has a story on the looming flu pandemic. The use a 1% case fatality rate, which is VERY optimistic. They also state that there has been no evidence of H5N1 mating and mutating, which is clearly wrong

http://www.recombinomics.com/H5N1_mating_mutating.html

 

[Aquamarine]

A more optimistic fatality rate may be due to assumptions of many unknown subclinical or mild infections. That seems to have been the case in Hong Kong 1997:
http://www.journals.uchicago.edu/JID/journal/issues/v181n1/990819/990819.text.html
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11930308&dopt=Citation

 

[niman]

It Is 2004

A more optimistic fatality rate may be due to assumptions of many unknown subclinical or mild infections. That seems to have been the case in Hong Kong 1997:
http://www.journals.uchicago.edu/JID/journal/issues/v181n1/990819/990819.text.html
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11930308&dopt=Citation

Check out the calendar. It is 2004. 1997 saw the first documented human H5N1 cases. 6 of the 18 confirmed cases died. That's a case fatality rate of 33%.

The H5N1 circulating in Asia has evolved quite a bit since 1997, which is why the 1997 pandemic vaccine is not very useful and a new vaccine is being prepared. Although there have not been in documented H5N1 human fatalities in China or Hong Kong, the H5N1 in Vietnam and Thailand has some unique polymorphisms

http://www.recombinomics.com/swine_human_signatures.html

and WHO has already acknowledge "probable" human to human transmission in Thailand

http://www.recombinomics.com/human_human_probable.html

The H5N1 in Thailand and Vietnam is Amantadine and Ramantadine resistant due to TWO mutations in M2. The case fatality rate in Vietnam and Thailand at the beginning of 2004 and more recently is in the 70-80% range, and acquisition of the human receptor binding domain could create more efficient human to human transmission, while maintaing the 70-80% case fatality rate.

http://www.recombinomics.com/H5N1_reassort_recombine.html

 

[Aquamarine]

The studies linked to previously seems to indicate that the fatality rate was much lower than 33% of those infected.

Regarding the recent outbreak in Vietnam:

We cannot rule out the possibility of mild or subclinical infection in persons exposed to either ill poultry or ill persons. Detailed seroepidemiologic studies of the individual family members, health care workers, and others at risk would be necessary in order to assess whether and to what extent human-to-human transmission has occurred.

http://content.nejm.org/cgi/content/full/350/12/1179?ck=nck

We can safely assume that the CDC and WHO knows more data than what is publicly available. For example, data on the frequency of subclinical infections that may not be good enough to publish in a peer-reviewed study. That may be why they are projecting a lower fatality rate.

Also, the current strain if H5N1 seems very virulent, for example in mice. But it may not be more virulent than that of 1918 (which if of course bad enough).

Using reverse genetics, Drs. Taubenberger, Palese, and others custom-built flu viruses that contained from two to five of the 1918 virus' eight genes, with the remaining genes originating from a flu strain that is adapted to mice. The study was published recently in the Proceedings of the National Academy of Sciences.

The researchers found that all viruses possessing 1918's hemagglutinin (HA) and neuraminidase (NA) genes were highly lethal to mice, a somewhat surprising discovery since genes from a human flu strain normally do not cause disease in mice.

http://www2.niaid.nih.gov/Newsroom/FocusOn/Flu04/toxic.htm

 

[niman]

The studies linked to previously seems to indicate that the fatality rate was much lower than 33% of those infected.

Regarding the recent outbreak in Vietnam:

http://content.nejm.org/cgi/content/full/350/12/1179?ck=nck

We can safely assume that the CDC and WHO knows more data than what is publicly available. For example, data on the frequency of subclinical infections that may not be good enough to publish in a peer-reviewed study. That may be why they are projecting a lower fatality rate.

Also, the current strain if H5N1 seems very virulent, for example in mice. But it may not be more virulent than that of 1918 (which if of course bad enough).

http://www2.niaid.nih.gov/Newsroom/FocusOn/Flu04/toxic.htm

Please. H5N1 has been identified in patients in Vietnam and Thailand and the case fatality rate is 70-80%. Citing other strains in other locations or times is pretty irrelevant. H3N2 has a lower case fatality rate and H5N1 is 2004 in locations other than Vietnam or Thailand have not been shown to infect humans.

WHO's lower rate is simply base on a misconception. They don't understand how influenza evolves. The cite reassortment, which merely shuffles genes. Swapping H3 for H5 would increase human to human transmission, but humans would have immunity to H3, so such a swap would not create a pandemic strain.

WHO doesn't know of any H5N1 asymptomatic carriers. Such a finding would be VERY big news and would be disclosed by WHO immediately.

The math is simple. WHO is lost in a reassortment haze. H5N1 evolves via recombination, which merely needs to swap the receptor binding domain between H5 and H3. The virus knows what it is doing. WHO does not.

http://www.recombinomics.com/H5N1_reassort_recombine.html

 

[KaneOris]

Im more worried about the super bug golden staf infections that are going around. No anti biotic currently available works against it!

 

[niman]

Case Mortality Rate

The studies linked to previously seems to indicate that the fatality rate was much lower than 33% of those infected.

We can safely assume that the CDC and WHO knows more data than what is publicly available. For example, data on the frequency of subclinical infections that may not be good enough to publish in a peer-reviewed study. That may be why they are projecting a lower fatality rate.

The media is now starting to cover the high case mortality rate (72%) as well as the mediaa age of fatal cases (13)

http://www.recombinomics.com/H5N1_case_mortality_rate.html

 

[Aquamarine]

Please. H5N1 has been identified in patients in Vietnam and Thailand and the case fatality rate is 70-80%. Citing other strains in other locations or times is pretty irrelevant. H3N2 has a lower case fatality rate and H5N1 is 2004 in locations other than Vietnam or Thailand have not been shown to infect humans.

WHO's lower rate is simply base on a misconception. They don't understand how influenza evolves. The cite reassortment, which merely shuffles genes. Swapping H3 for H5 would increase human to human transmission, but humans would have immunity to H3, so such a swap would not create a pandemic strain.

WHO doesn't know of any H5N1 asymptomatic carriers. Such a finding would be VERY big news and would be disclosed by WHO immediately.

The math is simple. WHO is lost in a reassortment haze. H5N1 evolves via recombination, which merely needs to swap the receptor binding domain between H5 and H3. The virus knows what it is doing. WHO does not.

http://www.recombinomics.com/H5N1_reassort_recombine.html

There is a broadcast http://www2.niaid.nih.gov/newsroom/FocusOn/Flu04 , where it is stated that they don't know if there are subclinical infections. This seems strange since they must have tested on poultry workers and health care workers in Vietnam and Thailand. I have been trying to understand the available avian flu diagnostics (not my area of expertise ). And it seems that it is not possible to determine the exact strain after an infection when the virus has left the body, only a broad type from antibodies? So guessing , I would suspect that there are antibodies in poultry workers and health care workers, like in Hong Kong, but is not possible to tell if it is from the current strain or from an earlier year. This would explain why they don't know if there are subclinical infections from the current strain. But that they are projecting the low fatality rate with the assumption that they are from the current strain?

Also, it seems to be possible to make some comparisons of the effect of the 1918 virus and the current one in animals, like mice. That may be another reason why they are projecting the current fatality rate.

Since the US government seems to be throwing money at http://www2.niaid.nih.gov/newsroom/focuson/flu04/research.htm related to this flu, I am surprised that they are not funding research on your theory. Are there some peer-reviewed papers supporting your claim that the WHO doesn't know what it it doing?

 

[Moonbear]

I'm not a virologist, and I haven't read all the links provided here. When I finish reading them, I may find the answer my own question, but I'll ask it anyway.

I see here a number of posts citing an incidence of only 18 reported cases with approx. 33% mortality rate. This strikes me as a very low number of cases to begin with. Is it possible that only those who are already in a high risk category for flu susceptibility are susceptible to even catching this strain? Maybe those with healthy immune systems don't even know they've been exposed? That would be one way of getting a very high mortality rate with a low incidence rate. Maybe closer to 100% of the people who catch this strain are the same people who would die from any other common strain going around now? These may also be the same people more susceptible to a virus jumping species? And maybe this is why the CDC is predicting a lower mortality estimate than the current data show?

Okay, now I'll go look and see if I find any of the answers to my own questions.

 

[Aquamarine]

I'm not a virologist, and I haven't read all the links provided here. When I finish reading them, I may find the answer my own question, but I'll ask it anyway.

I see here a number of posts citing an incidence of only 18 reported cases with approx. 33% mortality rate. This strikes me as a very low number of cases to begin with. Is it possible that only those who are already in a high risk category for flu susceptibility are susceptible to even catching this strain? Maybe those with healthy immune systems don't even know they've been exposed? That would be one way of getting a very high mortality rate with a low incidence rate. Maybe closer to 100% of the people who catch this strain are the same people who would die from any other common strain going around now? These may also be the same people more susceptible to a virus jumping species? And maybe this is why the CDC is predicting a lower mortality estimate than the current data show?

Okay, now I'll go look and see if I find any of the answers to my own questions.

It is mostly the young who have been killed by H5N1. This is consistent with what happened in 1918. In an ordinary flu it the old and sick who are killed.

One explanation may be that the old may have encountered a similar virus when they were young and now have some immunity. The great flu pandemics seem to come in intervals of thirty years. Maybe because then there is a new generation with no immunity?

CDC:
http://www.cdc.gov/flu/

WHO:
http://www.who.int/csr/disease/avian_influenza/en/

 

[Aquamarine]

A global pandemic of avian influenza is "very, very likely" and could kill tens of millions of people around the world, a top World Health Organization official said Monday.

Governments should be prepared to close schools, office buildings and factories in case of a pandemic, and should work out emergency staffing to prevent a breakdown in basic public services like electricity and transport, said Dr. Shigeru Omi, the organization's regional director for Asia and the Pacific.

Such arrangements may be needed if the disease infects 25 to 30 percent of the world's population, Omi said. That is the WHO's estimate for what could happen if the disease - currently found mainly in chickens, ducks and other birds - develops the ability to spread easily from person to person. Deaths associated with the rapid spread of a new form of influenza would be high, he said.

"We are talking at least 2 to 7 million, maybe more - 20 million or 50 million, or in the worst case, 100" million, he said.

http://www.iht.com/articles/2004/11/29/news/flu.html