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WHO H1N1 Pandemic Alert - Receptor Binding Domain Changes

Recombinomics Commentary 16:00
April 26, 2011

The Institute of Diagnosis and Epidemiological Reference (InDRE) of Mexico carried out genetic sequencing of the first three pandemic (H1N1) 2009 influenza cases (two fatal cases and one mild), and reported that the virus is homologous to the one that is currently circulating worldwide. Thus far, there is no evidence that the influenza strains identified have mutations that confer greater virulence or antiviral resistance. This outbreak occurred along the US-Mexico border region and has not been associated with excessive demand of the health services. In the rest of Mexico, isolated influenza A/H1N1 2009 cases have been reported, but there are no other outbreaks reported at this time.

Above is the carefully worded description of the initial sequences from the Chihuahua sub-clade as descibed in the PAHO week 12 update.  Much like the WHO press release after the Ukraine outbreak in the fall of 2009, the receptor binding domain changes are characterized as "insignificant".  The Ukraine changes, D225G and D225N, had been predicted because of jumping from one genetic background to another, as well as the association with severe and fatal cases, which was clear in the initial series of Ukraine sequences, as well as a much larger release of sequences from autopsy lung samples.

In the above Chihuahua sequences one of the samples from a fatal case had D225N, which was clearly linked to fatal cases in the Ukraine and the Duke Medical Center death cluster.  A subsequent sequence from Chihuahua had a mixture of D225N and D225G, as was seen in Ukraine.  However, the sequences from Chihuahua samples were from the upper respiratory tract, raising concerns of more efficient transmission.  This concern is increased by anecdotal reports of at least five additional samples with D225N as well as a sample with D225A. that was also found in the Ukraine autopsy samples.

The PAHO announcement claims “no evidence” for “great virulence”, but the sequence deposits from the above lab have the title “Detection of D222N substitution in Pandemic Influenza A (H1N1)Virus in Chihuahua, Mexico” leaving little doubt that the significance of the receptor binding domain change was appreciated by the sequencing lab.

Moreover, the claim that “This outbreak occurred along the US-Mexico border region and has not been associated with excessive demand of the health services” was contradicted two weeks later when the WHO H1N1 alert noted that the outbreaks in Ecuador, Venezuela, and Mexico did create excessive demand, which is consistent with anecdotal repots of patients with nose bleeds and breathing difficulties present at emergency rooms in Chihuahua and Nuevo Leon in northern Mexico.

Thus, release of the Chihuahua sequences with receptor binding domain changes, as well as sequences from severe and fatal cases from countries delineated in the WHO H1N1 pandemic alert, would be useful.

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