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Hazardous WHO Pandemic Hopes and Dreams
Recombinomics Commentary 12:11
August 10, 2010

The WHO has also been looking for evidence that -- as is normal with seasonal flu -- a variety of viruses are circulating. For months after H1N1's emergence, there was virtually no sign of other influenza A or influenza B viruses. Lately it's been much more of a mixed picture.

"In a nutshell I'm looking for several things," explains Chan, who concedes most of these criteria appear to have been satisfied.

"Lack of out-of-season outbreaks. Reduced intensity of outbreaks. And reduced dominance of the H1N1 pandemic virus and evidence of some population immunity (to the virus)."

Chan admits she's eager to move to the post-pandemic phase so the agency can focus on analyzing what happened and incorporating the knowledge gained into plans for future pandemics.

The above suggest that WHO will declare the end of the H1N1 pandemic today.  However, H1N1 does not read WHO press releases or the hopes and dreams of consultants.  The pandemic H1N1 is a swine virus that has jumped to humans, which has not happened in a sustained manner since 1918.  The similarities between the current strain, and 1918 pandemic H1N1 or seasonal H1N1 in circulation decades ago has led to a reduced infection rate among the elderly. 

However, the H1N1 virus can aggressively target those under 65, the demographic for over 90% of the fatalities.  These fatal cases are linked to the ability of the virus to target the lower respiratory tract, which has been linked to receptor binding domain changes such as D225G as well as low reactor alterations at positions 157-159.  Recently released 2010 sequence has demonstrated that these genetic changes are on the rise, raising concerns for the emergence of a more virulent H1N1 in the upcoming months or years.

The acquisition of these new markers via recombination has similarities with the fixing of H274Y in seasonal H1N1 in the 2008/2009 season.  H274Y confers Tamilfu resistance and began to appear in large numbers in seasonal H1N1 in selective countries in the 2007/2008 season.  Although levels approached or exceeded 50% of H1N1 isolates in northern Europe, the level was only 10% in countries like the US and UK, while countries in Asia, like South Korea had no reported cases and the level was only 3% in Japan, where use of Tamiflu in seasonal flu patients was widespread.  This distribution surprised and baffled WHO consultants, who maintained that small changes in influenza genes were due to random copy errors which were amplified by selection.  However, Tamiflu resistance in Japan was low in H1N1 and there was no reported resistance in H3N2 worldwide.  Moreover, all H1N1 resistance targeted the identical genetic change, which was present on multiple H1N1 genetic backgrounds.

In the summer of 2008, H274Y levels rose to 100% in H1N1 sequences in South Africa and Australia.  Although the overall levels of H1N1 were low, the fixing of H274Y in the southern hemisphere in the summer of 2008 spread to the northern hemisphere in the 2008/2009 and levels of 100% Tamiflu resistance were reported worldwide, including South Korea where the level was a 0% the previous year.

The potential for dramatic increases in D225G and low reactor changes at positions 157-159 remain and the current pandemic H1N1 continues to fatally infect those under 65,  WHO hopes and dreams and associated proclamations notwithstanding.

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