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GAO: United States Pandemic Plan is Unprepared
Recombinomics Commentary
May 30, 2005
>> While public health officials have undertaken several initiatives to enhance influenza surveillance capabilities, challenges remain with regard to other aspects of preparedness for and response to an influenza pandemic. In particular, HHS has not finalized planning for an influenza pandemic. In 2000, we recommended that HHS complete the national plan for responding to an influenza pandemic, but the plan has been in draft format since August 2004. Absent a completed federal plan, key questions about the federal role in the purchase, distribution, and administration of vaccines and antiviral drugs during a pandemic remain unanswered. Other challenges with regard to preparedness for and response to an influenza pandemic exist across the public and private sectors, including challenges in ensuring an adequate and timely influenza vaccine and antiviral supply; addressing regulatory, privacy, and procedural issues surrounding measures to control the spread of disease, for example, across national borders; and resolving issues related to an insufficient hospital and health workforce capacity for responding to a large-scale outbreak such as an influenza pandemic.
To be prepared for major public health threats such as an influenza pandemic, public health agencies need several basic capabilities, including disease surveillance systems. Specifically, to detect cases of pandemic influenza, especially before they develop into widespread outbreaks, local, state, and federal public health officials as well as international organizations collect, analyze, and share information related to cases of the disease. When effective, surveillance can facilitate timely action to control outbreaks and promote informed allocation of resources to meet changing disease conditions. <<
The above comments by the GAO indicate the United States flu pandemic preparedness plan needs a lot of work. It is appropriately called a draft, because the "plan" is full of holes. It plans for distributions of vaccines that don't exist, anti-virals that are not available, hospital beds that are not available, doctors and nurses that are not available, and a death rate that is much more wishful thinking than anything remotely approaching reality.
The draft was written in the summer of 2004. At that time it was quite clear that H5N1 in Asia posed a serious pandemic threat. H5N1 infections were reported throughout eastern Asia in unprecedented numbers of countries infected and numbers of animals and humans infected, especially in Vietnam and Thailand. Human-to-human transmission had already happened, in small clusters, placing the pandemic at phase 4. The H5N1 in Vietnam and Thailand was already resistant to 2 of the 4 FDA approved anti-virals, Amantadine and Rimantadine. The only anti-viral left that was available in quantity was Tamiflu, which was available in larger but limited amounts. WHO was still touting reassortment and included the fact that no human genes were found, each time a new isolate was sequenced. Pandemic projections relied on a dramatic reduction in case fatality rates based on a swapping of the entire H5 gene for a human H3 or H1 gene.
Thus, the 2004 draft was based on the 2004 virus and a number of misconceptions by WHO consultants. While the 2004 pandemic draft collected dust in the past 9 months, H5N1 continued to recombine and evolve, rendering the 2004 pandemic plan useless. However, the "final version" of the useless plan is scheduled for release in the summer. It is a cruel hoax that will be useful for burying the bodies, and not much else.
While the US draft was gathering dust, the 2005 flu pandemic moved from phase 4 to phase 5. The localized human-to-human clusters became larger and more frequent. A more aggressive screening may indicate that the clusters in northern Vietnam may have indeed merged and phase 5 may have already reached phase 6. This increased human- to- human transmissibility in northern Vietnam has been associated with a reduced case fatality rate from 70% to 20%, but is still markedly higher than the 0.2 - 0.3% used in the pandemic draft.
The increased transmissibility in northern Vietnam has been associated with genetic changes. One isolate is significantly different than the 2004 isolates being used in the pandemic vaccine. Another isolate has a mutation that makes the virus resistant to Tamiflu, the antiviral being stockpiled by many countries and only modestly so in the US. However, more common in the northern Vietnam isolates is a lost arginine in the HA cleavage site, indicating the virus is a recombinant, although WHO consultants will still call it a random mutation that just happens to be an exact match of the cleavage site in 2003 isolates from Hong Kong and Yunnan, and 2004 isolates from Yunnan, Gaungzhou, and Japan. The cleavage swap was via recombination, and these isolates also have changes near the receptor binding domain. These changes may be associated with the increased human-to-human transmissibility. However, like the swapping of the HA cleavage site, H5N1 can swap its entire avian receptor binding domain for a human receptor binding domain, allowing the H5N1 to be as transmissible as a human virus. This swap can be done without appreciable loss of virulence.
As the 2005 genetic data emerges it will be increasingly clear that H5N1 evolves via recombination. The 0.2-0.3% case fatality rates are based much more on wishful thinking than the evolution of H5N1 in southeast Asia.
However, even more dramatic than H5N1 evolution in southeast Asia is the H5N1 evolution in Qingahi China. The number of dead birds is over 1000. There are at least five different species that are H5N1 infected, and the die off is without precedent. In addition there are reports of 121 human deaths in 18 villages in the vicinity of the bird die off, as well as 6 tourists. The case fatality rate for these cases is above 60%. If verified, these numbers would dwarf any numbers in Vietnam and prove that high case fatality rates can be associated with efficient transmission, making the projections of deaths used in the pandemic draft meaningless.
The H5N1 in Qinghai would also probably not be recognized by antibodies generated by the pandemic vaccine. Tamiflu resistance would likely develop quickly.
Thus, the US really has no plan if the 2005 pandemic has reached phase 6 already, which may be the case for both southeast Asia and central China. Moreover, the problem in central China will likely spread throughout Asia by fall, which would render any US containment plan useless.
The US has wasted a year. H5N1 has not.
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