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Transmission of Fatal H1N1
Strain Accelerates Concerns

Recently released H1N1 sequences have significantly accelerated pandemic concerns. These sequences have receptor changes on the H1N1 virus which produce a case fatality rate at or near 100% in many countries.

These receptor binding domain changes are on multiple backgrounds, but the transmission and expansion of these fatal sequences in eastern Europe, including Russia, have increased concerns, as has the "low reactor" status as determined by sequences from the Ukraine pneumonic flu virus.

When reports from Ukraine described a high number of fatal cases associated with lung destruction and a hemorrhagic component, involvement of D225G and D225N receptor changes on the virus was predicted. However, although WHO had sent a team to Ukraine and had sent representative clinical samples to the CDC and WHO regional labs, the WHO characterized the sequence changes in the Ukraine as insignificant.

The association of D225G and D225N was more directly supported by sequences from the United States, Mexico, and Sweden, which identified samples with both D225G and D225N. Thus, once again two different changes were appended onto the same genetic background at a given location, but the background varied from location to location, supporting recombination. Moreover, in Mexico there were fatal infections with D225G and D225N. Both were in San Luis Potosi and collected with a day of each other, supporting transmission.

However, although the above data left little dount that the receptor binding changes were transmitting and jumping from one genetic background to the other via recombination, the WHO working hypothesis held that each of these changes was independent and due to copy errors within each patient.

This position had no support from the data. The changes at position 225 were only found in 1% of sequences, but were in six of six fatal cases in Ukraine. Similarly, isolates with both changes were found in two patients at the same location at the same time in Mexico. The WHO working hypothesis was yet another attempt to explain genetic drift by random mutation, even though the existing data offered no support for such a claim.

The recent data demonstrates a case fatality rate at or near 100% in multiple countries, with clustering of polymorphisms and patients consistent with transmission and recombination. Moreover, Mill Hill in London ran an antigenicity test on one of the Ukraine samples and found it to be a low reactor, raising concerns that changes at position 225 will become more common in the next H1N1 wave, which could have catastrophic consequences, while WHO is trying to construct a defense for its outdated random mutations as an explanation of genetic drift and viral evolution.

The transmission of a deadly H1N1, coupled with a WHO wedded to an outdated paradigm, significantly increases pandemic concerns.

Reference Sources 242

January 12, 2010

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