http://www.singtomeohmuse.com/viewtopic ... 9972#59972
Original Post by Monotreme at PlanforPandemic (link above)
A Very Severe Pandemic is Likely
In reviewing the US State Plans, I have come to the conclusion that there are many, including public health officials, who are apparently unaware of the facts pertaining to the risk of a severe pandemic. Since planning is heavily dependent on the assumptions made, it’s important that decision-makers, which includes the general public, understand why a severe pandemic is likely.
Definitions
I am defining a severe pandemic as a case fatality rate of at least 2%. I use the term very severe to mean a case fatality rate of at least 5%. I am only referring to virus, not to effect of the pandemic on society. I believe it is possible for society to survive a very severe pandemic, if adequate planning is done.
The H5N1 virus that originated in China in the 1990?s has novel properties.
* H5N1 is an influenza A virus. Like all flu A viruses, it mutates at a very rapid rate. (Chen and Holmes, 2006).
* It has already killed millions of birds and many different mammals (Animals Infected with H5N1).
* It has crossed the species-barrier and killed over 160 humans.(Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO)
* It has killed over 50% of the people it has infected, even with advanced medical care. (Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO)
* It preferentially kills school-age children and young adults. (Smallman-Raynor and Cliff, 2007)
* It kills in a similar way to the severe pandemic of 1918 - cytokine dysregulation (Kash et al. 2006)
H5N1 is widely dispersed.
* It has been found in animals in countries all over the world. (Countries where H5N1 has been found)
*It has infected many species of birds and mammals. (Animals Infected with H5N1).
* Experimental studies have demonstrated that it is highly lethal in mammals, and has gotten more lethal in mammals over time. (Maines et al. 2005)
* People in in many countries have been infected and killed by the virus. (Countries where H5N1 has been found)
* It is very unlikely that H5N1 will be eradicated in the foreseeable future.
* It is likely that H5N1 will continue to spread by migratory birds and other means to nearly every country in the world.
* It is likely that hundreds of millions, and possibly billions, of animals will be infected.
* Close association of hundreds of millions of people with hundreds of millions of infected animals provides many opportunities for adaptation of the virus to humans
H5N1 has already partially adapted to humans, the precursor to pandemic onset.
* Many clusters of human cases indicating human to human spread of H5N1 spread have been observed. (H5N1 Clusters)
* Clusters are becoming more frequent and larger. (Graph of Cluster Size and Frequency over Time)
* Human to Human to Human spread of H5N1 was observed in Karo, Indonesia (Karo cluster).
* Serial passage of the virus between humans selects for human adaptation.
* This adaptation has already occurred for the polymerase complex - H5N1 was recently shown to replicate at high levels in humans. (de Jong et al. 2006)
* Sustained transmission of H5N1 between humans is the only barrier left to pandemic onset. Given that H5N1 is already partially adapted to humans and the many opportunities it will have to finish it’s adaptation in the coming flu season, the risk that a pandemic will begin within the year is very high.
Although we don’t know what the kill rate of a pandemic strain of H5N1 will be, there is no reason to think that it will be less than the 1918 pandemic strain and many reasons to think that it will be worse, much worse. Historical arguments are non-scientific and ignore basic virology. Risk assessments of the likely severity of an H5N1 pandemic should be based on the very substantial data that has been collected on this virus and not based on what has happened in previous pandemics with different viruses.
Counter-arguments
There are some who portray themselves as experts on pandemic flu who suggest that if a pandemic occurs at all, it is likely to be mild and cannot possibly be worse than 1918. To be fair, I should represent their point-of-view (in italics) and explain why I think they are wrong.
The Historical Argument. There were three pandemics in the 20th century. Two were mild. One was severe (2% CFR). Therefore, a mild pandemic is most likely (2 out of 3). But if a severe pandemic occurs, it cannot have a CFR worse than 2% because that was the worst in the 20th century.
This argument is made by people who are ignorant of biology, which sadly includes many public health officials. Viruses do not read history books. Their behaviour is constrained by the laws of biology, not by statistics or history. Anyone who has worked with viruses has observed that many of them mutate very rapidly. This provides a rich substrate for individual variation. The very dense populations of humans that now exist in close proximity to a wide variety of animals provides historically unprecedented opportunities for viruses that infect animals to cross over to humans. Consequently, viruses with entirely novel properties are evolving and infecting humans. HIV/AIDS could never have been predicted based on history or statistics. It burst upon the world with no warning. It is a classic example of a virus that started in animals, apes, and now infects humans with nearly a 100% CFR (without treatment). With H5N1, we do have a warning. There are substantial bodies of data (listed above) suggesting that it is currently highly lethal and has partially adapted to humans without losing any of its lethality. These facts are relevant. What other flu viruses with different sequences did, is not.
The Virus Does Not Want to Kill its Host Argument. It is not in the viruses interest to kill its host. Therefore, H5N1 will, somehow, decrease its ability to kill in order to spread to more people. For some (unknown) reason, 2% is the maximum CFR it can have and still start a pandemic.
This argument is based on a deeply flawed understanding of evolution. Viruses are incapable of planning. Most of the variants that are produced die without replicating because the variations are detrimental. The key issue determining whether a viral variant will survive is whether it can replicate and infect a new host before it is destroyed in the original host. This is the only thing that matters. The ultimate fate of the original host is irrelevant. Example: HIV/AIDS. Without advanced medical treatment, HIV will kill nearly 100% of the hosts it infects. Yet, it has spread to millions of people. This is possible because it infects new hosts before it kills its original host. A pandemic strain of H5N1 could also kill nearly 100% of the hosts it infects because flu viruses spread to new hosts before the original host is very ill, just like HIV. For example, a 38 year old man in Indonesia infected with H5N1, reported having a mild cold on July 2, 2005 (WHO update 25). He did not go to a hospital until July 7, 2005. He was dead five days later. So, if he had been infected with a pandemic strain he would have been spreading H5N1 from July 1 until July 7, plenty of time to infect many people. The difference between HIV and H5N1 is that HIV takes a long time to spread to a new host and a long time to kill its original host. H5N1 kills quickly, but in a pandemic strain, would spread to new hosts even quicker. There is no biological reason why H5N1 cannot spread in a sustained manner with its current high fatality rate.
Expert Opinions
The people who make arguments against the possibility that H5N1 may become a pandemic strain without decreasing its kill rate are almost never virologists. What do real virologists think? Below (in italics) are the opinions of some of the most eminent virologists who have actually worked with H5N1.
From Webster et al. 2006, p. 7.
The H5N1 virus continues to evolve and spread, with additional human infections occurring in Vietnam, Cambodia, Indonesian, China, and Thailand. If this virus acquires human-to-human transmissibility with its present fatality rate of 50%, the resulting pandemic would be akin to a global tsunami. If it killed those infected at even a fraction of this rate, the results would be catastrophic.
[snip]
We cannot afford simply to hope that human-to-human spread of H5N1 will not happen and that, if it does, the pathogenicity of the virus will attenuate. Notably, the precursor of the severe acute respiratory syndrome (SARS)-associated coronavirus repeatedly crossed species barriers, probably for many years, before it finally acquired the capacity for human-to-human transmission, and its pathogenicity to humans was not attenuated.
[snip]
SARS was interrupted by early case detection and isolation, but influenza is transmissible early in the course of the disease and cannot be controlled by similar means.
From WHO Working Group, 21-22 September 2006 (p. 15)
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.
Conclusion
Given the available facts, failing to prepare for a very severe pandemic is irresponsible and likely to result in the deaths of hundreds of millions of people.
Additional References
H5N1 Outbreaks and Enzootic Influenza. (2006) Webster RG, Peiris M, Chen H, Guan Y.
Emerg Infect Dis. 12:3-8.
Influenza research at the human and animal interface. (2006) Report of a WHO working group. Geneva, Switzerland, 21-22 September.
Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam
The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host
Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus