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Withheld CDC H274Y H1N1Tamiflu Resistance Sequences
Recombinomics Commentary 14:30
June 30, 2011

The recent comments on detection of multiple neuraminidase resistance markers (S246N with H274Y or I222R) has increased concerns that such markers are more prevalent than reported.  This concern was increased by the failure of the CDC to release sequences from recent Delaware H1N1 isolates with H274Y. 

Earlier this season the CDC released four 2011 sequences from Delaware and four from Maryland and all eight sequences had H274Y.  All eight sequences were collected in February or March and represent the eight most recent isolates from these two states.  Phylogenetic analysis indicated H274Y was spreading via recombination and clonal expansion.  One of the sequences, A/Maryland/04/2011, was from the Chihuahua sub-clade, while the other seven were from the S188T sub-clade.  The first three sequences from Delaware had A189T, signaling clonal expansion.  Moreover, the fourth Delaware sequence, A/Delaware/08/2011, was virtually identical to A/Maryland/06/2011, signaling additional clonal expansion.  The H274Y was discovered through routine surveillance and was not linked to Tamiflu treatment raising concerns that the detection of H274Y in all eight of the most recent isolates from Delaware or Maryland signaled the start of significant spread of H274Y.
These concerns were increased when Delaware announced ten additional cases with H274Y, as determined by the CDC, supporting significant spread.  However, the recently released H1N1 sequences generated by the CDC did not include any of these ten samples or any additional samples from Delaware.  Similarly, the recently released sequences did not include any samples from new patients in Maryland.  The only Maryland sequence was an egg isolate of Maryland/04/2011 (which also had H274Y).  thus, although all eight of the most recent isolates from Maryland and Delaware, the CDC failed to release any additional 2011 sequences from any new patients, even though Delaware had announced that then CDC had confirmed 10 additional cases.

The withholding of these sequences by the CDC continues to increase pandemic concerns and evidence supporting the fixing of H274Y Tamiflu resistance in pandemic H1N1.

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