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Commentary
WHO H1N1 D225G
Transmission Omissions
Recombinomics
Commentary 21:28
February 04, 2010
To date no connection between cases, suggestive of transmission, has been found and it seems that the appearance in various countries is more the result of routine sequencing rather than spread of the mutation. It is also unclear if the association with severe cases is coincidental or not, perhaps resulting from preferred sequencing of specimens and viruses from severe cases/deaths.
These changes have been found since April 2009 but have not been associated with temporal or geographical clustering, strongly suggesting the mutation in these viruses has occurred sporadically as opposed to the emergence and sustained transmission of a variant virus.
The above comments are from WHO and ECDC documents that were directly or indirectly discussing the H1N1 receptor binding domain changes D225G and D225N. The first quote was from a WHO report on in hospital transmission of Tamiflu resistance (H274Y) in hospitals in the UK and US. The above quote was in reference to the US outbreak, which was at Duke Medical Center in mid-October. As noted above, 3 of the 4 infected patients died, which gave rise to the commentary questioning the role of D225G and D225N in the deaths.
The December 2 WHO reports was followed by December 28 reports by the ECDC and WHO on December 28. The WHO was also subsequently included in a WER e-mailing and posting on January 22. Both reports denied clustering or transmission of D225G.
However, sequences from the Duke Medical Center cluster were recently deposited at GISAID by the CDC. The samples were collected in mid-October and included 5 NA sequences with H274Y. All five isolates also had the rare HA marker Y233H, confirming that these samples were from a Tamiflu resistant cluster transmitting H2H.
However, three of these sequences also had D225G or D225N indicating these changes have aleo transmitted and well almost certainly linked to the fatal outcomes.
Since these cases were high profile (fatal transmission of Tamiflu resistance) and the subject of a December 2 report, the groups writing the papers on D225G should have been aware of the North Carolina death cluster since the sequences were generated by the CDC, a WHO regional center, and the linkage to D225G/N was of considerable import.
However, the reports on D225G released in 2009 and again in 2010 failed to disclose the D225G and D225N in the cluster.
This lack of transparency and denial of transmission raises serious pandemic concerns and continues to endanger the world’s health.
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