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The Global Reach of H5N1 Wild Bird Flu
September 2, 2005
My personal opinion, however, is that Dr. Gould is correct to query the relevance of the spread of avian influenza viruses by migratory birds as a factor in spread of human disease. It is more likely that a novel pandemic virus would spread along trade and communications routes rather than via the migratory pathways of free-living birds. The evidence so far is equivocal.
Outbreaks of disease have occurred along migratory routes, but the majority of migrating birds have proven to be free of H5N1 virus, and the minority of birds exhibiting disease may be victims rather than carriers of disease (the "dead birds do not migrate" hypothesis)……..
I favour Dr. Gould's contention that the current spate of accounts of
detection of H5N1-positive free-living birds is not particularly helpful and
requires critical evaluation. - Mod.CP]
The above commentary at ProMed is quite remarkable. ProMed is a widely read newsletter of the International Society for Infectious Diseases. Commentary that displays such a profound misunderstanding of the most basic molecular concepts is scandalous.
The Asian H5N1 version of avian influenza emerged in 1996 in Guangdong Province. The goose isolate contained a very unusual HA cleavage site with an unprecedented string of basic amino acids. The multi-basic amino acids correlated with HPIA (Highly Pathogenic Avian Influenza). The following year there was an outbreak of H5N1 in humans in Hong Kong. The reported human fatalities halted when all of the poultry in Hong Kong were culled. However, H5N1 in humans reappeared in a Hong Kong family in 2003. In 2004 the number of human cases reported in Vietnam and Thailand increased significantly. These case had a fatality rate of approximately 70%.
In association with the human cases, there was an explosion of H5N1 throughout eastern and southern Asia. The affected countries reported H5N1 for the first time in 2004. In several countries, H5N1 became endemic and human cases were again reported in 2005 in Vietnam, Cambodia, and Indonesia.
During this time H5N1 expanded its host range to wild and domestic cats and most recently to civet cats. In the lab it also caused disease in mice and ferrets. Thus, although it was an avian influenza virus, it was clearly expanding its host range.
This year it dramatically increased its geographical range via migratory birds. First reported at Qinghai Lake in China, the H5N1 was soon reported in Russia, Kazakhstan, and Mongolia. All of these reports were first for each country.
The H5N1 transport and transmission in these countries was quite efficient, running along the border shared by Russia and Kazakhstan to the west and by Russian and Mongolia to the east (see map). Now as the temperature in these areas falls, a further migration into Europe, Africa, and the Americas is expected. The establishment of H5N1 in migratory birds virtually assures a worldwide distribution in the next 12 months.
This dramatic spread has touched off alarm bells worldwide, yet commentaries at ProMed suggests there is little new, citing prior reports of low pathogenic avian influenza in migratory birds.
Sequence databases have isolates as old as 1902. Prior to the May, 2005 Qinghai Lake outbreak, there had been no reports of the PB2 mutation E627K in birds. The change is H5N1 was first reported in the 1997 human samples and it correlates with increased virulence in mammals. All of the Qingahi Lake isolates had this change and isolates from Qinghai Lake killed experimental chickens in 20 hours and mice in 3-4 days. The close homology between Qinghai lake isolates and Chany Lake isolates suggest that all of the H5N1 wild bird flu isolates have this change.
Thus, the dramatic spread of H5N1 into eastern and southern Asia in 2004 was without precedent and the likelihood that a similar geographical spread will happen in 2005 is high. Distribution of this virus worldwide increases the likelihood of a recombination event that will increase the efficiency of human to human transmission. Such a recombination could happen in avian or mammalian hosts.
The alarm bells are ringing loudly, but Alfred E Newman appears to be in charge at ProMed.